search
Back to results

Basket Study to Evaluate the Therapeutic Activity of Simlukafusp Alfa as a Combination Therapy in Participants With Advanced and/or Metastatic Solid Tumors

Primary Purpose

Advanced/Metastatic Head and Neck, Oesophageal and Cervical Cancers

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
simlukafusp alfa
Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody
Gemcitabine
Vinorelbine
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced/Metastatic Head and Neck, Oesophageal and Cervical Cancers

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Participants who have progressed on at least one previous regimen of anticancer therapy (chemotherapy, mutation targeted therapy, and/or CPI therapy)
  • Measurable disease, as defined by RECIST Version 1.1
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 or Karnofsky Performance Score greater than or equal to (>=) 70
  • Life expectancy of >=12 weeks
  • Confirmed at least one tumor lesion with location accessible to safely biopsy per clinical judgment of the treating physician.

Biopsies are not applicable to participants in Cohorts G, H, K, and L presenting with a single target lesion and absence of any non-target lesion.

  • Consent to provide an archival tumor tissue sample (if available, applicable to all participants)
  • Willingness to undergo baseline and on-treatment tumor biopsies for pharmacodynamics (PD) biomarker analysis (biopsies are optional for Cohort A)
  • Adequate cardiovascular function as defined in the study protocol
  • AEs related to any previous radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade less than or equal to (<=) 1, except alopecia (any grade) and Grade 2 peripheral neuropathy
  • Adequate haematological, liver, and renal functions.

  • Participants with unilateral pleural effusion (indications other than NSCLC) are eligible if they fulfill both of the following:

    1. NYHA Class 1
    2. Forced expiratory volume 1 (FEV1) and forced vital capacity (FVC) >70% of predicted value; participants with lung metastases should present with DLCO >60% of predicted value.
  • Participants with Gilbert's syndrome will be eligible for the study
  • Participants must have had confirmed diagnosis of recurrent or metastatic squamous cell carcinoma head and neck, or esophageal cancer or metastatic, persistent or recurrent squamous cervical cancer.

Exclusion Criteria:

  • Symptomatic or untreated central nervous system (CNS) metastases
  • History of treated asymptomatic CNS metastases as described in the protocol
  • Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >=2 weeks before enrollment
  • Leptomeningeal disease
  • An active second malignancy
  • Penetrating tumor infiltration
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
  • Episode of significant cardiovascular/cerebrovascular acute disease within 6 months before study treatment administration
  • History of significant vascular disease (for example, aortic aneurysm, aortic dissection)
  • Active or uncontrolled infections
  • Human immunodeficiency virus (HIV) or Active Hepatitis A, B, C, D or E infection (HAV/HBV/HCV/HDV/HEV).
  • Severe infection within 4 weeks before study treatment administration including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • History of chronic liver disease or evidence of hepatic cirrhosis
  • Dementia or altered mental status that would prohibit informed consent
  • History of, active or suspicion of autoimmune disease
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Bilateral pleural effusion confirmed by X-ray
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that give reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
  • Concurrent therapy with any other investigational drug
  • Immunomodulating agents as described in study protocol
  • Chronic use of steroids
  • Last dose with any cytostatic treatments < 28 days before study treatment administration
  • Radiotherapy within the last 4 weeks before start of study treatment administration, with the exception of limited field palliative radiotherapy
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1 or at any time during the study and 5 months after the last dose of atezolizumab
  • Major surgery or significant traumatic injury <28 days before study treatment administration (excluding fine needle biopsies) or if wound healing has not completed after surgery or anticipation of the need for major surgery during study treatment
  • Known hypersensitivity to any of the components of the simlukafusp alfa drug product or atezolizumab drug product
  • Severe dyspnea at rest or requiring supplementary oxygen therapy Locally curative options are available for participant's disease.

Sites / Locations

  • University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center
  • Cancer Treatment Centers of America
  • UZ Antwerpen
  • UZ Gent
  • UZ Leuven Gasthuisberg
  • Institut Bergonie
  • Hopital Timone Adultes; Oncologie Medicale Et Usp
  • ICM; Medecine B3
  • Gustave Roussy Cancer Campus
  • Universitätsklinikum Essen; Innere Klinik (Tumorforschung)
  • Rambam Medical Center; Oncology
  • Seoul National University Bundang Hospital
  • Severance Hospital, Yonsei University Health System
  • Seoul National University Hospital
  • Asan Medical Center
  • Samsung Medical Center
  • Auckland City Hospital; Clinical Oncology
  • Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz
  • Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Oddzial Badan Wczesnych Faz
  • N.N.Burdenko Main Military Clinical Hospital; Oncology Dept
  • S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
  • National University Hospital; National University Cancer Institute, Singapore (NCIS)
  • National Cancer Centre; Medical Oncology
  • Clinica Universitaria de Navarra
  • Hospital del Mar; Servicio de Oncologia
  • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Clinica Universidad de Navarra Madrid; Servicio de Oncología
  • Hospital Ramon y Cajal; Servicio de Oncologia
  • START Madrid-FJD, Hospital Fundacion Jimenez Diaz
  • START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
  • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
  • Hôpitaux Universit. de Genève Médecine Oncologie; Oncologie
  • National Cheng Kung Uni Hospital; Dept of Hematology and Oncology
  • National Taiwan Uni Hospital; Dept of Oncology
  • Adana Baskent University Hospital; Medical Oncology
  • Akdeniz University Medical Faculty; Medical Oncology Department
  • Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
  • Istanbul University Cerrahpa?a-Cerrahpa?a Medical Faculty; Medikal Onkoloji Departmani
  • ?zmir Medical Park; Onkoloji
  • Goztepe Prof.Dr. Suleyman Yalcin City Hospital; Clinical Oncology
  • Barts
  • University College London Hospital
  • Christie Hospital Nhs Trust; Medical Oncology
  • Royal Marsden Hospital; Institute of Cancer Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort A (Part I)

Cohort B (Part I)

Cohort C (Part I)

Cohort D Arm I (Part I)

Cohort D Arm 2 (Part I)

Cohort D Arm 3 (Part I)

Cohort E Arm I (Part II)

Cohort E Arm 2 (Part II)

Cohort F (Part I)

Cohort G (Part III)

Cohort H (Part III)

Cohort I (Part III)

Cohort J (Part III)

Cohort K (Part III)

Cohort L (Part III)

Cohort M (Part III)

Cohort N (Part III)

Arm Description

Checkpoint Inhibitor (CPI)-Naïve Participants with non-small-cell lung cancer (NSCLC) who have not received CPI therapy previously will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg. Tumor biopsies: collection of fresh tumor biopsies (at baseline and on-treatment) will be optional.

CPI-Experienced Participants (NSCLC) who have received CPI therapy previously will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.

This is a mandatory biopsy cohort based on the treatment's safety and preliminary activity analysis to enroll CPI-Naive Participants. Participants (NSCLC) will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.

CPI Experienced Participants (NSCLC) who were previously treated with platinum and docetaxel. Participants will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.

CPI Experienced Participants (NSCLC) who were previously treated with platinum and docetaxel. Participants will receive simlukafusp alfa intravenous (IV) infusion once in 3 weeks (Q3W) up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q3W at a dose of 1200 mg. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.

CPI Experienced Participants (NSCLC) who were previously treated with platinum and docetaxel will receive a single-agent gemcitabine or vinorelbine as per approved protocol. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.

This cohort will enroll participants (NSCLC) with High-Tumor PD-L1 Expression who have not received any prior systemic therapy. Participants will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.

This cohort will enroll participants (NSCLC) with High-Tumor PD-L1 Expression who have not received any prior systemic therapy. Participants will receive simlukafusp alfa IV infusion in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.

CPI-experienced, docetaxel naive participants (NSCLC) who experienced disease progression during or following treatment with a platinum - containing regimen. Participants will receive combination of simlukafusp alfa and atezolizumab in a Q3W schedule. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.

CPI-naïve SCC of the head and neck (SCCHN) (20 response-evaluable participants), mandatory biopsies. Participants in cohort G Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.

Previously treated, CPI-experienced squamous cell carcinoma head and heck cancer (20 response evaluable participants), mandatory biopsies. Participants in cohort H Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.

Previously treated, CPI-naïve squamous esophageal cancer (20 response evaluable participants), mandatory biopsies. Participants in cohort I Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.

Previously treated, CPI-naïve squamous cervical cancer (20 response evaluable participants): mandatory biopsy. Participants in cohort J Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.

CPI-naïve SCC of the head and neck (SCCHN) (20 response-evaluable participants), mandatory biopsies. Participants in cohort K Part III will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.

Previously treated, CPI-experienced squamous cell carcinoma head and neck cancer (20 response evaluable participants), mandatory biopsies. Participants in cohort L Part III will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.

Esophageal SCC participants will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.

Cervical SCC participants will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.

Outcomes

Primary Outcome Measures

Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
ORR was defined as the percentage of participants with observed tumor response of complete response (CR), or partial response (PR) determined according to RECIST version 1.1. CR was defined as the disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The percentages of participants are rounded off to the nearest single decimal point.

Secondary Outcome Measures

Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1
DCR was defined as the percentage of participants with observed tumor response of CR, PR or stable disease (SD) determined according to RECIST version 1.1. CR was defined as the disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline (nadir). The percentages of participants are rounded off to the nearest single decimal point.
Duration of Response (DoR) According to RECIST Version 1.1
DoR was determined for participants who had a best overall response of CR or PR. CR was defined as the disappearance of all target lesions with a reduction in target/non-target pathological lymph nodes to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. DoR was defined as the time from first occurrence of a documented objective response until the time of documented disease progression or death from any cause during treatment, whichever occurs first. Participants that did not have documented progressive disease or death during the study were censored at the day of the last tumor assessment.
Progression-Free Survival (PFS) According to RECIST Version 1.1
PFS was defined as the time from study treatment initiation (Cycle 1 Day 1 [1 cycle=14 days for QW/Q2W cohorts; 1 cycle=21 days for Q3W cohorts]) to the first occurrence of documented disease progression (based on Investigator's assessment) or death from any cause during treatment, whichever occurs first. Participants that did not have documented progressive disease or death during the study were censored at the day of the last tumor assessment.
Overall Survival (OS)
OS was defined as the time from the first dose of study treatment to the time of death from any cause on study. Participants who were still alive at the time of analysis were censored at the last date known alive.
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Percentage of Participants by Programmed Death-Ligand 1 (PD-L1) Status According to Immunohistochemical Methods
Change From Baseline in Density of Cluster of Differentiation (CD) 8 Positive (CD8+) Cells According to Immunohistochemical Methods
Change From Baseline in Density of Cluster of Differentiation 3 Negative (CD3-) Perforin Positive Cells According to Immunohistochemical Methods
Change From Baseline in Density of PD-L1 According to Immunohistochemical Methods

Full Information

First Posted
December 22, 2017
Last Updated
February 20, 2023
Sponsor
Hoffmann-La Roche
search

1. Study Identification

Unique Protocol Identification Number
NCT03386721
Brief Title
Basket Study to Evaluate the Therapeutic Activity of Simlukafusp Alfa as a Combination Therapy in Participants With Advanced and/or Metastatic Solid Tumors
Official Title
An Open-Label, Multicenter, Phase II Study to Evaluate the Therapeutic Activity of Simlukafusp Alfa (RO6874281), an Immunocytokine, Consisting of Interleukin-2 Variant (IL-2v) Targeting Fibroblast Activation Protein-Α (FAP), in Combination With Atezolizumab (Anti-PD-L1), Administered Intravenously, in Participants With Advanced and/or Metastatic Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
The Sponsor discontinued the development of Simlukafusp alfa due to portfolio prioritization, not due to any safety, efficacy, or quality issues.
Study Start Date
February 19, 2018 (Actual)
Primary Completion Date
December 30, 2021 (Actual)
Study Completion Date
December 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is an open-label, multicenter, basket trial Phase II study to evaluate the antitumor activity of simlukafusp alfa in combination with atezolizumab in participants with advanced and/or metastatic solid tumors. Currently the focus is on participants with Head and Neck, oesophageal and cervical cancers with confirmed squamous cell carcinoma histology type.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced/Metastatic Head and Neck, Oesophageal and Cervical Cancers

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
256 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort A (Part I)
Arm Type
Experimental
Arm Description
Checkpoint Inhibitor (CPI)-Naïve Participants with non-small-cell lung cancer (NSCLC) who have not received CPI therapy previously will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg. Tumor biopsies: collection of fresh tumor biopsies (at baseline and on-treatment) will be optional.
Arm Title
Cohort B (Part I)
Arm Type
Experimental
Arm Description
CPI-Experienced Participants (NSCLC) who have received CPI therapy previously will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
Arm Title
Cohort C (Part I)
Arm Type
Experimental
Arm Description
This is a mandatory biopsy cohort based on the treatment's safety and preliminary activity analysis to enroll CPI-Naive Participants. Participants (NSCLC) will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
Arm Title
Cohort D Arm I (Part I)
Arm Type
Experimental
Arm Description
CPI Experienced Participants (NSCLC) who were previously treated with platinum and docetaxel. Participants will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
Arm Title
Cohort D Arm 2 (Part I)
Arm Type
Experimental
Arm Description
CPI Experienced Participants (NSCLC) who were previously treated with platinum and docetaxel. Participants will receive simlukafusp alfa intravenous (IV) infusion once in 3 weeks (Q3W) up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q3W at a dose of 1200 mg. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
Arm Title
Cohort D Arm 3 (Part I)
Arm Type
Experimental
Arm Description
CPI Experienced Participants (NSCLC) who were previously treated with platinum and docetaxel will receive a single-agent gemcitabine or vinorelbine as per approved protocol. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
Arm Title
Cohort E Arm I (Part II)
Arm Type
Experimental
Arm Description
This cohort will enroll participants (NSCLC) with High-Tumor PD-L1 Expression who have not received any prior systemic therapy. Participants will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
Arm Title
Cohort E Arm 2 (Part II)
Arm Type
Experimental
Arm Description
This cohort will enroll participants (NSCLC) with High-Tumor PD-L1 Expression who have not received any prior systemic therapy. Participants will receive simlukafusp alfa IV infusion in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
Arm Title
Cohort F (Part I)
Arm Type
Experimental
Arm Description
CPI-experienced, docetaxel naive participants (NSCLC) who experienced disease progression during or following treatment with a platinum - containing regimen. Participants will receive combination of simlukafusp alfa and atezolizumab in a Q3W schedule. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
Arm Title
Cohort G (Part III)
Arm Type
Experimental
Arm Description
CPI-naïve SCC of the head and neck (SCCHN) (20 response-evaluable participants), mandatory biopsies. Participants in cohort G Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.
Arm Title
Cohort H (Part III)
Arm Type
Experimental
Arm Description
Previously treated, CPI-experienced squamous cell carcinoma head and heck cancer (20 response evaluable participants), mandatory biopsies. Participants in cohort H Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.
Arm Title
Cohort I (Part III)
Arm Type
Experimental
Arm Description
Previously treated, CPI-naïve squamous esophageal cancer (20 response evaluable participants), mandatory biopsies. Participants in cohort I Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
Arm Title
Cohort J (Part III)
Arm Type
Experimental
Arm Description
Previously treated, CPI-naïve squamous cervical cancer (20 response evaluable participants): mandatory biopsy. Participants in cohort J Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
Arm Title
Cohort K (Part III)
Arm Type
Experimental
Arm Description
CPI-naïve SCC of the head and neck (SCCHN) (20 response-evaluable participants), mandatory biopsies. Participants in cohort K Part III will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.
Arm Title
Cohort L (Part III)
Arm Type
Experimental
Arm Description
Previously treated, CPI-experienced squamous cell carcinoma head and neck cancer (20 response evaluable participants), mandatory biopsies. Participants in cohort L Part III will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.
Arm Title
Cohort M (Part III)
Arm Type
Experimental
Arm Description
Esophageal SCC participants will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
Arm Title
Cohort N (Part III)
Arm Type
Experimental
Arm Description
Cervical SCC participants will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
Intervention Type
Drug
Intervention Name(s)
simlukafusp alfa
Other Intervention Name(s)
RO6874281
Intervention Description
simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody
Intervention Description
Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Single-agent treatment administered as per approved protocol.
Intervention Type
Drug
Intervention Name(s)
Vinorelbine
Intervention Description
Single-agent treatment administered as per approved protocol.
Primary Outcome Measure Information:
Title
Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Description
ORR was defined as the percentage of participants with observed tumor response of complete response (CR), or partial response (PR) determined according to RECIST version 1.1. CR was defined as the disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The percentages of participants are rounded off to the nearest single decimal point.
Time Frame
Baseline up to disease progression or study treatment discontinuation (up to 38 months)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1
Description
DCR was defined as the percentage of participants with observed tumor response of CR, PR or stable disease (SD) determined according to RECIST version 1.1. CR was defined as the disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline (nadir). The percentages of participants are rounded off to the nearest single decimal point.
Time Frame
Baseline up to disease progression or study treatment discontinuation (up to 38 months)
Title
Duration of Response (DoR) According to RECIST Version 1.1
Description
DoR was determined for participants who had a best overall response of CR or PR. CR was defined as the disappearance of all target lesions with a reduction in target/non-target pathological lymph nodes to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. DoR was defined as the time from first occurrence of a documented objective response until the time of documented disease progression or death from any cause during treatment, whichever occurs first. Participants that did not have documented progressive disease or death during the study were censored at the day of the last tumor assessment.
Time Frame
From first occurrence of documented CR or PR up to disease progression or study treatment discontinuation (assessed every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 38 months)
Title
Progression-Free Survival (PFS) According to RECIST Version 1.1
Description
PFS was defined as the time from study treatment initiation (Cycle 1 Day 1 [1 cycle=14 days for QW/Q2W cohorts; 1 cycle=21 days for Q3W cohorts]) to the first occurrence of documented disease progression (based on Investigator's assessment) or death from any cause during treatment, whichever occurs first. Participants that did not have documented progressive disease or death during the study were censored at the day of the last tumor assessment.
Time Frame
Study treatment initiation up to disease progression or study treatment discontinuation (up to 38 months)
Title
Overall Survival (OS)
Description
OS was defined as the time from the first dose of study treatment to the time of death from any cause on study. Participants who were still alive at the time of analysis were censored at the last date known alive.
Time Frame
From first dose of study treatment up to death due to any cause (up to approximately 47 months)
Title
Percentage of Participants With Adverse Events (AEs)
Description
An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame
Baseline up to end of the study (up to approximately 47 months)
Title
Percentage of Participants by Programmed Death-Ligand 1 (PD-L1) Status According to Immunohistochemical Methods
Time Frame
Baseline
Title
Change From Baseline in Density of Cluster of Differentiation (CD) 8 Positive (CD8+) Cells According to Immunohistochemical Methods
Time Frame
Baseline up 2 months
Title
Change From Baseline in Density of Cluster of Differentiation 3 Negative (CD3-) Perforin Positive Cells According to Immunohistochemical Methods
Time Frame
Baseline up to 2 months
Title
Change From Baseline in Density of PD-L1 According to Immunohistochemical Methods
Time Frame
Baseline up to 2 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants who have progressed on at least one previous regimen of anticancer therapy (chemotherapy, mutation targeted therapy, and/or CPI therapy) Measurable disease, as defined by RECIST Version 1.1 Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 or Karnofsky Performance Score greater than or equal to (>=) 70 Life expectancy of >=12 weeks Confirmed at least one tumor lesion with location accessible to safely biopsy per clinical judgment of the treating physician. Biopsies are not applicable to participants in Cohorts G, H, K, and L presenting with a single target lesion and absence of any non-target lesion. Consent to provide an archival tumor tissue sample (if available, applicable to all participants) Willingness to undergo baseline and on-treatment tumor biopsies for pharmacodynamics (PD) biomarker analysis (biopsies are optional for Cohort A) Adequate cardiovascular function as defined in the study protocol AEs related to any previous radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade less than or equal to (<=) 1, except alopecia (any grade) and Grade 2 peripheral neuropathy Adequate haematological, liver, and renal functions. Participants with unilateral pleural effusion (indications other than NSCLC) are eligible if they fulfill both of the following: NYHA Class 1 Forced expiratory volume 1 (FEV1) and forced vital capacity (FVC) >70% of predicted value; participants with lung metastases should present with DLCO >60% of predicted value. Participants with Gilbert's syndrome will be eligible for the study Participants must have had confirmed diagnosis of recurrent or metastatic squamous cell carcinoma head and neck, or esophageal cancer or metastatic, persistent or recurrent squamous cervical cancer. Exclusion Criteria: Symptomatic or untreated central nervous system (CNS) metastases History of treated asymptomatic CNS metastases as described in the protocol Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >=2 weeks before enrollment Leptomeningeal disease An active second malignancy Penetrating tumor infiltration Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results Episode of significant cardiovascular/cerebrovascular acute disease within 6 months before study treatment administration History of significant vascular disease (for example, aortic aneurysm, aortic dissection) Active or uncontrolled infections Human immunodeficiency virus (HIV) or Active Hepatitis A, B, C, D or E infection (HAV/HBV/HCV/HDV/HEV). Severe infection within 4 weeks before study treatment administration including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. History of chronic liver disease or evidence of hepatic cirrhosis Dementia or altered mental status that would prohibit informed consent History of, active or suspicion of autoimmune disease History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted Bilateral pleural effusion confirmed by X-ray Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that give reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug Concurrent therapy with any other investigational drug Immunomodulating agents as described in study protocol Chronic use of steroids Last dose with any cytostatic treatments < 28 days before study treatment administration Radiotherapy within the last 4 weeks before start of study treatment administration, with the exception of limited field palliative radiotherapy Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1 or at any time during the study and 5 months after the last dose of atezolizumab Major surgery or significant traumatic injury <28 days before study treatment administration (excluding fine needle biopsies) or if wound healing has not completed after surgery or anticipation of the need for major surgery during study treatment Known hypersensitivity to any of the components of the simlukafusp alfa drug product or atezolizumab drug product Severe dyspnea at rest or requiring supplementary oxygen therapy Locally curative options are available for participant's disease.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Cancer Treatment Centers of America
City
Newnan
State/Province
Georgia
ZIP/Postal Code
30265
Country
United States
Facility Name
UZ Antwerpen
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Leuven Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Institut Bergonie
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Hopital Timone Adultes; Oncologie Medicale Et Usp
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
ICM; Medecine B3
City
Montpellier cedex 5
ZIP/Postal Code
34298
Country
France
Facility Name
Gustave Roussy Cancer Campus
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Universitätsklinikum Essen; Innere Klinik (Tumorforschung)
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Rambam Medical Center; Oncology
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Seoul National University Bundang Hospital
City
Seongnam-si
ZIP/Postal Code
13620
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
003-722
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Auckland City Hospital; Clinical Oncology
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand
Facility Name
Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz
City
Gda?sk
ZIP/Postal Code
80-214
Country
Poland
Facility Name
Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Oddzial Badan Wczesnych Faz
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland
Facility Name
N.N.Burdenko Main Military Clinical Hospital; Oncology Dept
City
Moscow
ZIP/Postal Code
105229
Country
Russian Federation
Facility Name
S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
City
Saint-Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
Facility Name
National University Hospital; National University Cancer Institute, Singapore (NCIS)
City
Singapore
ZIP/Postal Code
119228
Country
Singapore
Facility Name
National Cancer Centre; Medical Oncology
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
Facility Name
Clinica Universitaria de Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital del Mar; Servicio de Oncologia
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Hospital Univ Vall d'Hebron; Servicio de Oncologia
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Clinica Universidad de Navarra Madrid; Servicio de Oncología
City
Madrid
ZIP/Postal Code
28027
Country
Spain
Facility Name
Hospital Ramon y Cajal; Servicio de Oncologia
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
START Madrid-FJD, Hospital Fundacion Jimenez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Hôpitaux Universit. de Genève Médecine Oncologie; Oncologie
City
Geneve
ZIP/Postal Code
1211
Country
Switzerland
Facility Name
National Cheng Kung Uni Hospital; Dept of Hematology and Oncology
City
Tainan
ZIP/Postal Code
704
Country
Taiwan
Facility Name
National Taiwan Uni Hospital; Dept of Oncology
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Facility Name
Adana Baskent University Hospital; Medical Oncology
City
Adana
ZIP/Postal Code
01120
Country
Turkey
Facility Name
Akdeniz University Medical Faculty; Medical Oncology Department
City
Antalya
ZIP/Postal Code
07070
Country
Turkey
Facility Name
Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
City
Edirne
ZIP/Postal Code
22030
Country
Turkey
Facility Name
Istanbul University Cerrahpa?a-Cerrahpa?a Medical Faculty; Medikal Onkoloji Departmani
City
Istanbul
ZIP/Postal Code
34098
Country
Turkey
Facility Name
?zmir Medical Park; Onkoloji
City
Izmir
Country
Turkey
Facility Name
Goztepe Prof.Dr. Suleyman Yalcin City Hospital; Clinical Oncology
City
Kadiköy
ZIP/Postal Code
34722
Country
Turkey
Facility Name
Barts
City
London
ZIP/Postal Code
EC1M6BQ
Country
United Kingdom
Facility Name
University College London Hospital
City
London
ZIP/Postal Code
N7 9NH
Country
United Kingdom
Facility Name
Christie Hospital Nhs Trust; Medical Oncology
City
Manchester
ZIP/Postal Code
M2O 4BX
Country
United Kingdom
Facility Name
Royal Marsden Hospital; Institute of Cancer Research
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Learn more about this trial

Basket Study to Evaluate the Therapeutic Activity of Simlukafusp Alfa as a Combination Therapy in Participants With Advanced and/or Metastatic Solid Tumors

We'll reach out to this number within 24 hrs