Investigating the Effects of Atezolizumab in People Whose Tumour DNA or RNA Indicates Possible Sensitivity

NCT04273061 | Recruiting Phase 2

• 1 other identifier: H19-04010
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

This study will investigate the effects of atezolizumab on select cancer types in people whose analysis of tumour DNA and RNA indicates they may be sensitive to atezolizumab. This study aims to determine if the information from the cancer genome analysis corresponds with the effects of atezolizumab on individuals and their cancer. This is a Phase 2 study, which is undertaken after preliminary safety testing on a drug is completed, and will involve approximately 200 participants. Participants are assigned to one of 8 cohorts based on their primary tumour type: breast, lung, gastrointestinal (GI), primary unknown, genitourinary (GU), sarcoma, gynecological, and 'other' cancer types. Participants in all cohorts will receive the same dose of atezolizumab (1200 mg every 3 weeks). In the first stage for each cohort, 8 participants will be enrolled and if no participants respond to treatment, enrollment to that cohort will be closed. If 1 or more participants respond to treatment, up to 16 additional participants will be enrolled to that cohort. Participants continue on treatment until they no longer may benefit from the treatment or they decide to stop treatment.

Conditions

Breast Cancer; Lung Cancer; Gastrointestinal Cancer; Genitourinary Cancer; Gynecologic Cancer; Sarcoma; Unknown Primary Tumors; Head and Neck Cancer; Skin Cancer

Keywords

Genomic analysis; Atezolizumab; Whole genome and transcriptome analysis; Immune Burden Variant score; Immune checkpoint inhibition; Personalized OncoGenomics; Phase 2; Precision targeting

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR) in each tumour-defined cohort, as defined by RECIST 1.1

  The proportion of participants in each tumour-defined cohort who have a complete response (CR) or partial response (PR) to treatment, as defined by RECIST 1.1.

  From the date of the screening scan (within 28 days of first dose) until the date of confirmed progression, withdrawal, or date of death, whichever comes first, assessed up to 54 months.

Secondary Outcomes (5)

• Progression-free survival (PFS) in each tumour-defined cohort from the initiation of atezolizumab

  From the date of first dose until the date of confirmed progression, withdrawal, or date of death, whichever comes first, assessed up to 54 months.

• Clinical benefit rate (CBR) in each tumour-defined cohort at the 18-week follow-up scan

  From the date of the screening scan (within 28 days of first dose) until the date of the 18-week follow-up scan.

• Overall survival (OS) in each tumour-defined cohort from the initiation of atezolizumab

  From the date of first dose until the date of death, assessed up to 54 months.

• Quality-adjusted survival in each tumour-defined cohort from the initiation of atezolizumab

  From the date of first dose until the treatment discontinuation visit (within 30 days of last dose), withdrawal, or date of death, whichever comes first, assessed up to 54 months.

• Duration of response (DoR) in each tumour-defined cohort

  From the date of the scan that shows the first response to treatment until the date of progression, withdrawal, or date of death, whichever comes first, assessed up to 54 months.

Other Outcomes (4)

• Putative markers of sensitivity to atezolizumab in each tumour-defined cohort

  From the date of screening sample collection until the date of progression, withdrawal, or date of death, whichever comes first, assessed up to 54 months.

• Putative primary and secondary resistance markers to atezolizumab in each tumour-defined cohort

  From the date of screening sample collection until the date of progression, withdrawal, or date of death, whichever comes first, assessed up to 54 months.

• Putative germline predictors of adverse events or toxicities of interest in each tumour-defined cohort

  From the date of screening sample collection until the date of progression, withdrawal, or date of death, whichever comes first, assessed up to 54 months.

Study Arms (8)

Breast Cohort

EXPERIMENTAL

Cohort of participants whose primary tumour type is breast.

Drug: Atezolizumab

Lung Cohort

EXPERIMENTAL

Cohort of participants whose primary tumour type is lung.

Drug: Atezolizumab

GI Cohort

EXPERIMENTAL

Cohort of participants whose primary tumour type is gastrointestinal (including pancreas and hepatobiliary).

Drug: Atezolizumab

GU Cohort

EXPERIMENTAL

Cohort of participants whose primary tumour type is genitourinary.

Drug: Atezolizumab

Gyne Cohort

EXPERIMENTAL

Cohort of participants whose primary tumour type is gynecological.

Drug: Atezolizumab

Sarcoma Cohort

EXPERIMENTAL

Cohort of participants whose primary tumour type is sarcoma.

Drug: Atezolizumab

Primary Unknown Cohort

EXPERIMENTAL

Cohort of participants whose primary tumour type is unknown.

Drug: Atezolizumab

Other Cohort

EXPERIMENTAL

Cohort of participants whose primary tumour type is not classified as one of the other study arms. This cohort includes participants with cancers from the head and neck, skin, or rare cancers.

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

1200 mg by intravenous infusion every 3 weeks as tolerated

Also known as: TECENTRIQ

Breast Cohort; GI Cohort; GU Cohort; Gyne Cohort; Lung Cohort; Other Cohort; Primary Unknown Cohort; Sarcoma Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18 years at the time of signature of informed consent.
• Participants with an incurable solid tumour who have undergone whole genome and transcriptome analysis (WGTA) as part of Personalized OncoGenomics (POG) or equivalent program.
• a. Participants must have had successful sequencing of their tumour, been formally reviewed by the POG (or POG-approved) genome analysts and found to have CAPTIV-8 factors identified (including Immune, Burden, Variant (IBV) score ≥ 5), been reviewed at the Molecular Tumour Board (MTB) (or site equivalent), and allocated to a specific tumour-defined cohort (that is open for enrolment) with a final opinion documented.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Participants must have measurable disease, as defined by RECIST 1.1.
• Life expectancy of at least 12 weeks.
• Adequate hematologic and end-organ function, as defined by the following laboratory results obtained within 28 days prior to the first study treatment:
• Absolute neutrophil count (ANC) ≥ 1500 cells/µL without granulocyte colony- stimulating factor support.
• White blood cell (WBC) counts \> 2500/µL.
• Lymphocyte count ≥ 500/µL.
• Serum albumin ≥ 2.5 g/dL.
• Platelet count ≥ 100,000/µL without transfusion (without transfusion within 2 weeks of laboratory test used to determine eligibility).
• Hemoglobin ≥ 9.0 g/dL, participants may be transfused or receive erythropoietic treatment to meet this criterion.
• International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 × Upper Limit of Normal (ULN). This applies only to participants who are not receiving therapeutic anticoagulation; participants receiving therapeutic anticoagulation must have an INR or aPTT within therapeutic limits for at least 1 week prior to enrolment.
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 × ULN with the following exceptions: i) Participants with documented liver metastases: AST and/or ALT ≤ 5 × ULN. ii) Participants with documented liver or bone metastases: ALP ≤ 5 × ULN.

You may not qualify if:

• Any prior treatment with monoclonal antibodies targeting the Programmed Death 1/Ligand (PD-1/PD-L1) axis, including antibody-drug conjugates and other experimental agents.
• Treatment with any approved or investigational agent or participation in another clinical trial with therapeutic intent within 14 days or five half-lives of the drug, whichever is longer, prior to enrollment. Participants receiving gonadotropin releasing hormone (GnRH) analogues may continue to receive treatment while participating in CAPTIV-8.
• Pregnancy or breastfeeding.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation.
• Active autoimmune disease at any point within the last 2 years prior to enrollment including but not limited to:
• Myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
• Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone may be eligible for this study.
• Participants with controlled Type I diabetes mellitus on a stable dose of insulin regimen are eligible for this study.
• Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., participants with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
• Rash must cover less than 10% (ten percent) of body surface area (BSA).
• Disease is well controlled at baseline and only requiring low potency topical steroids.
• No acute exacerbations of underlying condition within the last 12 months requiring treatment with either psoralen plus ultraviolet radiation (PUVA), methotrexate, retinoids, biologic agents, oral calcineurin inhibitors or high potency or oral steroids.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Positive test for HIV (participants with a history of/or symptoms of HIV are eligible only if serological tests are negative).

Sponsors & Collaborators

• British Columbia Cancer Agency: lead
• Hoffmann-La Roche: collaborator

Study Sites (2)

BC Cancer

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

University Health Network / Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

WITHDRAWN

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MeSH Terms

Conditions

Breast Neoplasms; Lung Neoplasms; Gastrointestinal Neoplasms; Urogenital Neoplasms; Sarcoma; Neoplasms, Unknown Primary; Head and Neck Neoplasms; Skin Neoplasms

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Janessa Laskin, MD

  BC Cancer

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Janessa Laskin, MD

CONTACT

800-663-3333; jlaskin@bccancer.bc.ca

Daniel Renouf, MD, MPH

CONTACT

800-663-3333; drenouf@bccancer.bc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Simon 2-stage design; 8 tumour-defined cohorts consisting of 8 to 24 participants each.

Study Record Dates

• First Submitted: February 13, 2020
• First Posted: February 17, 2020
• Study Start: June 17, 2020
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)