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Avelumab With Bempegaldesleukin With or Without Talazoparib or Enzalutamide in Advanced or Metastatic Solid Tumors

Primary Purpose

Squamous Cell Carcinoma of the Head and Neck (SCCHN), Metastatic Castration Resistant Prostate Cancer (mCRPC)

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

avelumab

Bempegaldesleukin

talazoparib

enzalutamide

About this trial

This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Eligibility Criteria

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

Inclusion Criteria:

Participants must be ≥ 18 years old.
Participants with SCCHN or mCRCP.
Participants must have histological diagnosis of solid tumors and provide tumor tissue.
Measurable disease by RECIST v1.1 with at least 1 measurable lesion.
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
Adequate bone marrow, renal and liver function
Highly effective contraceptive use by men with the ability to father a child or women of childbearing potential.
A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) at C1D1.
Signed and dated informed consent.

Exclusion Criteria:

Known prior severe hypersensitivity to investigational products or any component in their formulations, including known severe hypersensitivity reactions to monocolonal antibodies.
Known history of: immune-mediated colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis.
Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
Prior organ transplantation including allogenic stem cell transplantation.
Vaccination within 4 weeks prior to C1D1 and while on trial is prohibited except for administration of inactivated vaccines.
Known symptomatic brain lesions requiring steroids.
Known history of testing positive for human immunodeficiency virus (HIV or known acquired immunodeficiency syndrome (AIDS).
Positive HBV surface antigen or HCV test indicating acute or chronic infection..
Active infection requiring systemic therapy
Clinically significant (i.e., active) cardiovascular disease including the following: documented left ventricular ejection fraction (LVEF) <50% by ECHO/MUGA; cerebral vascular accident/stroke or transient ischemic attack; myocardial infarction; unstable angina; congestive heart failure or serious cardiac arrhythmia (uncontrolled, clinically significant) requiring medication.
Diagnosis of any other malignancy within 2 years prior to C1D1, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix and for Combination A only, low-grade (Gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (e.g., surgery, radiation, or castration) or adequately treated prostate cancer.
Current use of immunosuppressive medication at the time of study enrollment.
Major surgery within 4 weeks prior to study enrollment.
Conditions that may impair intake or absorption such as inability to swallow capsules or tablets; known malabsorption syndrome; or baseline diarrhea ≤ Grade 1.
Participation in other studies involving investigational drug(s) within 2 weeks prior to C1D1.

Sites / Locations

University of Rochester Medical Center
GZA Ziekenhuizen campus Sint-Augustinus
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
Hospital Quirón Barceloma
Hospital Universitari Vall d'Hebron

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Combination A

Combination B

Combination C

Arm Description

Avelumab + Bempegaldesleukin (NKTR-214) for treatment of locally recurrent (not amendable for treatment with curative intent) or metastatic squamous cell carcinoma of the head and neck

Avelumab + Bempegaldesleukin (NKTR-214) + Talazoparib for treatment of metastatic castration-resistant prostate cancer (mCRPC). Phase 2 will focus on enrolling participants with DDR defect positive mCRPC.

Combination C: Avelumab + Bempegaldesleukin (NKTR-214) + Enzalutamide for Treatment of mCRPC

Outcomes

Primary Outcome Measures

Number of Participants With Dose Limiting Toxicities (DLT)

DLTs were graded according to NCI- CTCAE version 4.03 and coded using the latest version of Medical Dictionary for Regulatory Activities (MedDRA) preferred term (PT) as event category and MedDRA primary system organ class (SOC) body term as Body System category.

Secondary Outcome Measures

Duration of Response (DR)

DR was defined, for participants with a confirmed Objective Response (OR), as the time from the first documentation of OR to the date of first documentation of progressive disease (PD) or death due to any cause. The documentation of PD was defined using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. If a subject had not had an event (PD or death), DR was censored at the date of last adequate tumor assessment. As there were no objective responses in the study, no participant met the definition of analysis population.

Time to Tumor Response (TTR)

TTR was defined, for participants with objective response, as the time from the date of first dose of study treatment to the first documentation of objective response (Complete Response or Partial Response) which was subsequently confirmed. As there were no objective responses in the study, no participant met the definition of analysis population.

Progression-Free Survival (PFS)

Progression-Free Survival (PFS) was defined as the time from the date of first dose of study treatment to the date of the first documentation of PD or death due to any cause, whichever occurred first. PFS data were censored on the date of the last adequate tumor assessment for participants who did not have an event (PD or death), for participants who started new anti-cancer therapy prior to an event, or for participants with an event after two or more missing tumor assessments. Participants who did not have an adequate baseline tumor assessment or who did not have any adequate post-baseline tumor assessments were censored on the date of first dose of study treatment unless death occurred on or before the time of the second planned tumor assessment, in which case the death was considered an event. PFS time was summarized using the Kaplan-Meier method.

Overall Survival (OS)

Overall survival (OS) was defined as the time from the date of first dose of study treatment to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. OS time was summarized using the Kaplan-Meier method.

Pharmacokinetic (PK) Parameters - Cmax and Ctrough for Avelumab and NKTR-214

Cmax was defined as the maximum observed plasma concentration at the end of infusion. Ctrough was defined as the predose concentration at the end of dosing interval.

Number of Participants With Positive Anti-Drug Antibody (ADA) Results

ADA against avelumab and NKTR-214 in serum samples was determined and reported separately for ADA never-positive, ADA ever-positive participants, baseline ADA positive, treatment-boosted ADA, treatment-induced ADA, transient ADA response, persistent ADA response. For all participants, blood for ADA samples was drawn from the contralateral arm of the avelumab and NKTR-214 infusion.

Number of Participants With Positive Neutralizing Antibody (nAb) Results

nAb in serum samples was determined and reported separately for nAb never-positive, nAb ever-positive, baseline nAb positive, treatment-induced nAb, transient nAb response, persistent nAb response.

PD-L1 Expression Level in Baseline and On-treatment Tumor Tissue

PD-L1 expression level in baseline tumor tissue, and in on-treatment tumor tissue was defined as the number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and/or inflammatory cells in regions of interest. PD-L1 expression level in baseline tumor tissue and in on-treatment tumor tissue were under pathological analyses, assisted by image analysis. Participants were classified as positive or negative according to scoring algorithms and cut-offs established from internal or external sources.

Number of Participants With Treatment-Emergent Adverse Events(TEAEs), Serious TEAEs, TEAEs Leading to Death and Infusion-Related Reactions (IRRs) During On-treatment Period

Adverse events (AEs) were any untoward medical occurrences in a participant or clinical study participants, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-emergent adverse events (TEAEs) were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as the time from the first dose of study treatment through minimum (30 days + last dose of study treatment). A Serious Adverse Event (SAE) was defined as any untoward medical occurrence that, at any dose: a. Results in death, b. Was life-threatening, c. Required inpatient hospitalization or prolongation of existing hospitalization, d. Resulted in persistent disability/incapacity, e. Was a congenital anomaly/birth defect. Causality to study treatment was determined by the investigator.

Number of Participants With Laboratory Abnormalities With NCI-CTCAE Grade >= 3 - Safety Analysis Set

Liver Function Tests of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBILI) were used to assess possible drug induced liver toxicity. The number of participants with at least one of the following laboratory results were summarized below: 1. (ALT ≥3 × ULN or AST ≥3 × ULN) post-baseline. 2. TBILI ≥2 × ULN post-baseline. 3. (ALP ≤2 × ULN or missing) post-baseline.

Full Information

NCT ID

NCT04052204

First Posted

August 2, 2019

Last Updated

September 17, 2021

Sponsor

Pfizer

Collaborators

EMD Serono, Nektar Therapeutics, Astellas Pharma Inc

1. Study Identification

Unique Protocol Identification Number

NCT04052204

Brief Title

Avelumab With Bempegaldesleukin With or Without Talazoparib or Enzalutamide in Advanced or Metastatic Solid Tumors

Official Title

A Phase 1b/2 Study to Evaluate Safety and Clinical Activity of Avelumab in Combination With Bempegaldesleukin(NKTR-214) With or Without Talazoparib or Enzalutamide in Participants With Locally Advanced or Metastatic Solid Tumors

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Terminated

Why Stopped

Study prematurely terminated as the experimental treatments evaluated in study B9991040 may not provide additional clinical benefit over current or future Standard of Care in the different therapeutic indications that this trial was to evaluate.

Study Start Date

December 30, 2019 (Actual)

Primary Completion Date

September 29, 2020 (Actual)

Study Completion Date

September 29, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

Collaborators

EMD Serono, Nektar Therapeutics, Astellas Pharma Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

Evaluation of the combination of avelumab + bempegaldesleukin (NKTR-214 ) in locally advanced squamous cell carcinoma of the head and neck ( metastatic SCCHN) and avelumab + bempegaldesleukin (NKTR-214) + talazoparib or enzalutamide in metastatic castration resistant prostate cancer (mCRPC).

Detailed Description

Phase 1b/ Phase 2 Design Phase 1b will be the sequential dose-finding study. Once the Phase 1b component is completed, Phase 2 will be initiated to further evaluate the safety and anti-tumor activity across combinations of therapy. Combination A will enroll participants with SCCHN. Combination B and C will enroll participants with mCRPC

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Squamous Cell Carcinoma of the Head and Neck (SCCHN), Metastatic Castration Resistant Prostate Cancer (mCRPC)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Model Description

Combination A: Avelumab + Bempegaldesleukin (NKTR-214) for treatment of locally recurrent (not amendable for treatment with curative intent) or metastatic squamous cell carcinoma of the head and neck Combination B: Avelumab + Bempegaldesleukin (NKTR-214) + Talazoparib for treatment of metastatic castration-resistant prostate cancer (mCRPC). Phase 2 will enroll participants with DDR defect positive mCRPC. Combination C: Avelumab + Bempegaldesleukin (NKTR-214) + Enzalutamide for Treatment of mCRPC

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Combination A

Arm Type

Experimental

Arm Description

Avelumab + Bempegaldesleukin (NKTR-214) for treatment of locally recurrent (not amendable for treatment with curative intent) or metastatic squamous cell carcinoma of the head and neck

Arm Title

Combination B

Arm Type

Experimental

Arm Description

Arm Title

Combination C

Arm Type

Experimental

Arm Description

Combination C: Avelumab + Bempegaldesleukin (NKTR-214) + Enzalutamide for Treatment of mCRPC

Intervention Type

Drug

Intervention Name(s)

avelumab

Other Intervention Name(s)

Bavencio, MSB0010718C

Intervention Description

Investigational fully human anti-PD-L1 monoclonal antibody

Intervention Type

Drug

Intervention Name(s)

Bempegaldesleukin

Other Intervention Name(s)

NKTR-214

Intervention Description

Investigational CD122-biased cytokine agonist

Intervention Type

Drug

Intervention Name(s)

talazoparib

Other Intervention Name(s)

Talzenna

Intervention Description

poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitor

Intervention Type

Drug

Intervention Name(s)

enzalutamide

Other Intervention Name(s)

Xtandi

Intervention Description

androgen receptor inhibitor

Primary Outcome Measure Information:

Title

Number of Participants With Dose Limiting Toxicities (DLT)

Description

Time Frame

Cycle 1 of the treatment period (28 days)

Secondary Outcome Measure Information:

Title

Duration of Response (DR)

Description

Time Frame

Approximately 8 months (246 days).

Title

Time to Tumor Response (TTR)

Description

Time Frame

Approximately 8 months (246 days).

Title

Progression-Free Survival (PFS)

Description

Time Frame

Approximately 8 months (246 days).

Title

Overall Survival (OS)

Description

Time Frame

Approximately 8 months (246 days).

Title

Pharmacokinetic (PK) Parameters - Cmax and Ctrough for Avelumab and NKTR-214

Description

Cmax was defined as the maximum observed plasma concentration at the end of infusion. Ctrough was defined as the predose concentration at the end of dosing interval.

Time Frame

Blood samples were collected on Day 1 and Day 15 in Cycle 1 and Cycle 2 for avelumab. Blood samples were collected on Day 1, Day 3, Day 4 and Day 8 in Cycle 1, Day1 and Day 8 in Cycle 2 for NKTR-214.

Title

Number of Participants With Positive Anti-Drug Antibody (ADA) Results

Description

Time Frame

Day 1 of Cycle 1, 2 and end of treatment (EOT).

Title

Number of Participants With Positive Neutralizing Antibody (nAb) Results

Description

nAb in serum samples was determined and reported separately for nAb never-positive, nAb ever-positive, baseline nAb positive, treatment-induced nAb, transient nAb response, persistent nAb response.

Time Frame

Day 1 of Cycle 1, 2 and EOT

Title

PD-L1 Expression Level in Baseline and On-treatment Tumor Tissue

Description

Time Frame

On-treatment biopsy is required to be collected on Cycle 1 between Days 9 and 14 for participants in Combination A.

Title

Number of Participants With Treatment-Emergent Adverse Events(TEAEs), Serious TEAEs, TEAEs Leading to Death and Infusion-Related Reactions (IRRs) During On-treatment Period

Description

Time Frame

Approximately 6 months (190 days)

Title

Number of Participants With Laboratory Abnormalities With NCI-CTCAE Grade >= 3 - Safety Analysis Set

Description

Time Frame

Day 1, Day 15 of each treatment cycle

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participants must be ≥ 18 years old. Participants with SCCHN or mCRCP. Participants must have histological diagnosis of solid tumors and provide tumor tissue. Measurable disease by RECIST v1.1 with at least 1 measurable lesion. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1. Adequate bone marrow, renal and liver function Highly effective contraceptive use by men with the ability to father a child or women of childbearing potential. A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) at C1D1. Signed and dated informed consent. Exclusion Criteria: Known prior severe hypersensitivity to investigational products or any component in their formulations, including known severe hypersensitivity reactions to monocolonal antibodies. Known history of: immune-mediated colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis. Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Prior organ transplantation including allogenic stem cell transplantation. Vaccination within 4 weeks prior to C1D1 and while on trial is prohibited except for administration of inactivated vaccines. Known symptomatic brain lesions requiring steroids. Known history of testing positive for human immunodeficiency virus (HIV or known acquired immunodeficiency syndrome (AIDS). Positive HBV surface antigen or HCV test indicating acute or chronic infection.. Active infection requiring systemic therapy Clinically significant (i.e., active) cardiovascular disease including the following: documented left ventricular ejection fraction (LVEF) <50% by ECHO/MUGA; cerebral vascular accident/stroke or transient ischemic attack; myocardial infarction; unstable angina; congestive heart failure or serious cardiac arrhythmia (uncontrolled, clinically significant) requiring medication. Diagnosis of any other malignancy within 2 years prior to C1D1, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix and for Combination A only, low-grade (Gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (e.g., surgery, radiation, or castration) or adequately treated prostate cancer. Current use of immunosuppressive medication at the time of study enrollment. Major surgery within 4 weeks prior to study enrollment. Conditions that may impair intake or absorption such as inability to swallow capsules or tablets; known malabsorption syndrome; or baseline diarrhea ≤ Grade 1. Participation in other studies involving investigational drug(s) within 2 weeks prior to C1D1.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pfizer CT.gov Call Center

Organizational Affiliation

Pfizer

Official's Role

Study Director

Facility Information:

Facility Name

University of Rochester Medical Center

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

Facility Name

GZA Ziekenhuizen campus Sint-Augustinus

City

Wilrijk

State/Province

Antwerpen

ZIP/Postal Code

2610

Country

Belgium

Facility Name

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy

City

Warszawa

State/Province

Mazowieckie

ZIP/Postal Code

02-781

Country

Poland

Facility Name

Hospital Quirón Barceloma

City

Barcelona

ZIP/Postal Code

08023

Country

Spain

Facility Name

Hospital Universitari Vall d'Hebron

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

IPD Sharing URL

https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Links:

URL

https://pmiform.com/clinical-trial-info-request?StudyID=B9991040

Description

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Avelumab With Bempegaldesleukin With or Without Talazoparib or Enzalutamide in Advanced or Metastatic Solid Tumors

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