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Study of RO7515629 in Participants With HLA-G Positive Solid Tumors

Primary Purpose

Renal Cell Carcinoma, Non-small Cell Lung Cancer, Pancreatic Adenocarcinoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RO7515629
tocilizumab
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Renal Cell Carcinoma focused on measuring HLA-G, Human leukocyte antigen G, Renal cell carcinoma, Non-small cell lung cancer, Pancreatic adenocarcinoma, Colorectal cancer, Epithelial ovarian cancer, Primary peritoneal cancer, Fallopian tube cancer, RO7515629, Tocilizumab

Eligibility Criteria

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

Inclusion Criteria: Unresectable and/or metastatic HLA-G-positive solid tumors, for which standard therapy does not exist, or has proven to be ineffective or intolerable The following tumor histologies will be permitted: Part 1: renal cell carcinoma (clear cell, papillary, chromophobe or unclassified), non-small cell lung cancer (squamous or non-squamous), pancreatic adenocarcinoma, epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer of the following subtype: serous high-grade carcinoma Part 2: renal cell carcinoma (clear cell, papillary, chromophobe or unclassified), non-small cell lung cancer (squamous or non-squamous), pancreatic adenocarcinoma, colorectal cancer, epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer of the following subtype: serous high-grade carcinoma Part 3: renal cell carcinoma with a clear-cell component; must have IMDC poor or intermediate risk disease and must have received no more than 3 prior systemic therapies in the advanced or metastatic setting (prior treatment must include an immune checkpoint inhibitor) Confirmed HLA-G tumor expression. Participants without archival tumor tissue available for testing must have a lesion amenable to biopsy. Radiologically measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 For part I only: non-measurable evaluable disease is acceptable. For participants in part 1 with epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer: participants without a measurable lesion must have evaluable disease and/or have CA-125 greater than 2 times the upper limit of normal (ULN). Life expectancy of at least 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate hematological, liver, renal and pulmonary function Willingness to abide by protocol defined contraceptive requirements for the duration of the study. Exclusion Criteria: History or clinical evidence of Central Nervous System (CNS) metastases unless protocol specified criteria are met Leptomeningeal metastases Rapid disease progression including lesions that are a threat to vital organs or non-irradiated lesions 2cm or larger at critical sites where tumor swelling may pose a risk to critical anatomical structures Participants with another invasive malignancy in the last 2 years unless protocol specified criteria are met Uncontrolled hypertension Active interstitial lung disease (ILD), pneumonitis or a history of ILD/pneumonitis requiring treatment with steroids, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest Computed Tomography (CT) scan Participants with >10 bilateral pulmonary lesions (i.e., at least one lesion in each lung and more than 10 lung lesions in total) or pulmonary miliary metastatic pattern or pulmonary lymphangitic carcinomatosis History of pulmonary embolism within 3 months prior to study entry Significant cardiovascular disease Presence of active or uncontrolled infection or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to initiation of study treatment. Known hepatitis B or C (actively replicating) based on protocol specified criteria Known Human Immunodeficiency Virus (HIV) positivity Presence of an indwelling line or drain Active auto-immune disease that has required systemic therapy within the past 2 years unless protocol specified exceptions are met Major surgery within 28 days prior to first study treatment Last treatment with anti-cancer therapy or any investigational drug 28 days or less prior to the first study treatment Last dose of immunostimulating or immunosuppressive therapy 28 days or less prior to the first study treatment Regular dose of corticosteroids that exceeds prednisone 10 mg/day or equivalent within 28 days prior to first study treatment Prior treatment with T cell engaging or adoptive cell therapy Administration of a live, attenuated vaccine 28 days or less prior to first study treatment Contraindication or known hypersensitivity to any of the components of RO7515629 or tocilizumab or dexamethasone

Sites / Locations

  • Sarah Cannon Research Institute at HealthONERecruiting
  • Tennessee Oncology; Sarah Cannon Research InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Part I Single Participant Cohort RO7515629 Dose Escalation

Part II Multiple Participant Cohort RO7515629 Dose Escalation

Part III Multiple Participant Cohort RO7515629 Dose Expansion

Arm Description

Participants will receive a fixed dose of RO7515629 intravenously as a single agent on cycle 0 day -7 and 7 days later on cycle 1 day 1 followed by every three-week dosing frequency. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.

Participants will receive RO7515629 intravenously, as a single agent on cycle 0 day -7 and 7 days later on cycle 1 day 1 followed by every three-week dosing frequency. In case of toxicity, step up dosing (single or double) may be implemented. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.

Participants with selected solid tumors will receive a selected dose of RO7515629 intravenously as a single agent based on the recommended dose sequence for expansion (RDE) and dosing regimen selected from Part I and Part II. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.

Outcomes

Primary Outcome Measures

Part 1, 2, 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Part 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs)

Secondary Outcome Measures

Part 1, 2, 3: Pharmacokinetic Analysis: Maximum Serum Concentration (Cmax) of RO7515629
Part 1, 2, 3: Pharmacokinetic Analysis: Time of Maximum Serum Concentration (Tmax) of RO7515629
Part 1, 2, 3: Pharmacokinetic Analysis: Minimum Serum Concentration (Cmin) of RO7515629
Parts 1, 2, 3: Pharmacokinetic Analysis: Clearance (CL) of RO7515629
Part 1, 2, 3: Pharmacokinetic Analysis: Volume of Distribution at Steady State (Vss) of RO7515629
Part 1, 2, 3: Pharmacokinetic Analysis: Area Under The Curve (AUC) of RO7515629
Part 1, 2, 3: Number of Participants With RO7515629 Anti-drug Antibodies (ADAs)
Part 1, 2, 3: Objective Response Rate (ORR)
Part 1, 2, 3: Disease Control Rate (DCR)
Part 1, 2, 3: Duration of Response (DoR)
Part 1, 2, 3: Progression Free Survival (PFS)
Part 1, 2, 3: Overall survival (OS)
Defined as the time from first dose of study treatment to time of death.

Full Information

First Posted
March 3, 2023
Last Updated
October 20, 2023
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT05769959
Brief Title
Study of RO7515629 in Participants With HLA-G Positive Solid Tumors
Official Title
An Open-Label, Multicenter, Phase 1 Study to Evaluate Safety, Pharmacokinetics, and Preliminary Anti-Tumor Activity of RO7515629 in Participants With Unresectable and/or Metastatic HLA-G Positive Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 15, 2023 (Actual)
Primary Completion Date
January 29, 2027 (Anticipated)
Study Completion Date
January 29, 2027 (Anticipated)

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
The main purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, immune response and preliminary anti-tumor activity of RO7515629 alone in participants with advanced or metastatic solid tumors expressing human leukocyte antigen G (HLA-G).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Cell Carcinoma, Non-small Cell Lung Cancer, Pancreatic Adenocarcinoma, Colorectal Cancer, Ovarian Neoplasms
Keywords
HLA-G, Human leukocyte antigen G, Renal cell carcinoma, Non-small cell lung cancer, Pancreatic adenocarcinoma, Colorectal cancer, Epithelial ovarian cancer, Primary peritoneal cancer, Fallopian tube cancer, RO7515629, Tocilizumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part I Single Participant Cohort RO7515629 Dose Escalation
Arm Type
Experimental
Arm Description
Participants will receive a fixed dose of RO7515629 intravenously as a single agent on cycle 0 day -7 and 7 days later on cycle 1 day 1 followed by every three-week dosing frequency. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.
Arm Title
Part II Multiple Participant Cohort RO7515629 Dose Escalation
Arm Type
Experimental
Arm Description
Participants will receive RO7515629 intravenously, as a single agent on cycle 0 day -7 and 7 days later on cycle 1 day 1 followed by every three-week dosing frequency. In case of toxicity, step up dosing (single or double) may be implemented. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.
Arm Title
Part III Multiple Participant Cohort RO7515629 Dose Expansion
Arm Type
Experimental
Arm Description
Participants with selected solid tumors will receive a selected dose of RO7515629 intravenously as a single agent based on the recommended dose sequence for expansion (RDE) and dosing regimen selected from Part I and Part II. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.
Intervention Type
Drug
Intervention Name(s)
RO7515629
Intervention Description
RO7515629 will be administered intravenously at a dose and schedule as specified for the respective study part and cohort.
Intervention Type
Drug
Intervention Name(s)
tocilizumab
Other Intervention Name(s)
Actemra, RoActemra
Intervention Description
Tocilizumab will be used as rescue medication only. Tocilizumab will be administered as required for the management of cytokine release syndrome (CRS).
Primary Outcome Measure Information:
Title
Part 1, 2, 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Up to 15 months
Title
Part 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame
From start of study treatment (cycle 0 day -7 or cycle 0 day -14) until two weeks after second or third RO7515629 infusion (cycle 1 day 1) for a total DLT window of up to 28 days.
Secondary Outcome Measure Information:
Title
Part 1, 2, 3: Pharmacokinetic Analysis: Maximum Serum Concentration (Cmax) of RO7515629
Time Frame
Up to 13 months
Title
Part 1, 2, 3: Pharmacokinetic Analysis: Time of Maximum Serum Concentration (Tmax) of RO7515629
Time Frame
Up to 13 months
Title
Part 1, 2, 3: Pharmacokinetic Analysis: Minimum Serum Concentration (Cmin) of RO7515629
Time Frame
Up to 13 months
Title
Parts 1, 2, 3: Pharmacokinetic Analysis: Clearance (CL) of RO7515629
Time Frame
Up to 13 months
Title
Part 1, 2, 3: Pharmacokinetic Analysis: Volume of Distribution at Steady State (Vss) of RO7515629
Time Frame
Up to 13 months
Title
Part 1, 2, 3: Pharmacokinetic Analysis: Area Under The Curve (AUC) of RO7515629
Time Frame
Up to 13 months
Title
Part 1, 2, 3: Number of Participants With RO7515629 Anti-drug Antibodies (ADAs)
Time Frame
Up to 13 months
Title
Part 1, 2, 3: Objective Response Rate (ORR)
Time Frame
Up to approximately 18 months
Title
Part 1, 2, 3: Disease Control Rate (DCR)
Time Frame
Up to approximately 18 months
Title
Part 1, 2, 3: Duration of Response (DoR)
Time Frame
Up to approximately 18 months
Title
Part 1, 2, 3: Progression Free Survival (PFS)
Time Frame
Up to approximately 18 months
Title
Part 1, 2, 3: Overall survival (OS)
Description
Defined as the time from first dose of study treatment to time of death.
Time Frame
Up to approximately 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Unresectable and/or metastatic HLA-G-positive solid tumors, for which standard therapy does not exist, or has proven to be ineffective or intolerable The following tumor histologies will be permitted: Part 1: renal cell carcinoma (clear cell, papillary, chromophobe or unclassified), non-small cell lung cancer (squamous or non-squamous), pancreatic adenocarcinoma, epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer of the following subtype: serous high-grade carcinoma Part 2: renal cell carcinoma (clear cell, papillary, chromophobe or unclassified), non-small cell lung cancer (squamous or non-squamous), pancreatic adenocarcinoma, colorectal cancer, epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer of the following subtype: serous high-grade carcinoma Part 3: renal cell carcinoma with a clear-cell component; must have IMDC poor or intermediate risk disease and must have received no more than 3 prior systemic therapies in the advanced or metastatic setting (prior treatment must include an immune checkpoint inhibitor) Confirmed HLA-G tumor expression. Participants without archival tumor tissue available for testing must have a lesion amenable to biopsy. Radiologically measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 For part I only: non-measurable evaluable disease is acceptable. For participants in part 1 with epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer: participants without a measurable lesion must have evaluable disease and/or have CA-125 greater than 2 times the upper limit of normal (ULN). Life expectancy of at least 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate hematological, liver, renal and pulmonary function Willingness to abide by protocol defined contraceptive requirements for the duration of the study. Exclusion Criteria: History or clinical evidence of Central Nervous System (CNS) metastases unless protocol specified criteria are met Leptomeningeal metastases Rapid disease progression including lesions that are a threat to vital organs or non-irradiated lesions 2cm or larger at critical sites where tumor swelling may pose a risk to critical anatomical structures Participants with another invasive malignancy in the last 2 years unless protocol specified criteria are met Uncontrolled hypertension Active interstitial lung disease (ILD), pneumonitis or a history of ILD/pneumonitis requiring treatment with steroids, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest Computed Tomography (CT) scan Participants with >10 bilateral pulmonary lesions (i.e., at least one lesion in each lung and more than 10 lung lesions in total) or pulmonary miliary metastatic pattern or pulmonary lymphangitic carcinomatosis History of pulmonary embolism within 3 months prior to study entry Significant cardiovascular disease Presence of active or uncontrolled infection or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to initiation of study treatment. Known hepatitis B or C (actively replicating) based on protocol specified criteria Known Human Immunodeficiency Virus (HIV) positivity Presence of an indwelling line or drain Active auto-immune disease that has required systemic therapy within the past 2 years unless protocol specified exceptions are met Major surgery within 28 days prior to first study treatment Last treatment with anti-cancer therapy or any investigational drug 28 days or less prior to the first study treatment Last dose of immunostimulating or immunosuppressive therapy 28 days or less prior to the first study treatment Regular dose of corticosteroids that exceeds prednisone 10 mg/day or equivalent within 28 days prior to first study treatment Prior treatment with T cell engaging or adoptive cell therapy Administration of a live, attenuated vaccine 28 days or less prior to first study treatment Contraindication or known hypersensitivity to any of the components of RO7515629 or tocilizumab or dexamethasone
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: BP44068 https://forpatients.roche.com/
Phone
888-662-6728 (U.S. and Canada)
Email
global-roche-genentech-trials@gene.com
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
Sarah Cannon Research Institute at HealthONE
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Name
Tennessee Oncology; Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
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

Study of RO7515629 in Participants With HLA-G Positive Solid Tumors

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