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

Phase 2

Recruiting

• Conditions: Breast Cancer; Gastrointestinal Cancer; Genitourinary Cancer; Skin Cancer; Lung Cancer; Gynecologic Cancer; Head and Neck Cancer; Sarcoma; Unknown Primary Tumors
• Interventions: Drug: Atezolizumab

• Registration Number: NCT04273061
• Lead Sponsor: British Columbia Cancer Agency

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-02-13
• Study First Submitted QC: 2020-02-14
• Study First Posted: 2020-02-17
• Study Start: 2020-06-17
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-19
• Last Update Posted: 2024-08-21
• Primary Completion: 2027-10
• Study Completion: 2027-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• 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:

  1. Absolute neutrophil count (ANC) ≥ 1500 cells/µL without granulocyte colony- stimulating factor support.
  2. White blood cell (WBC) counts > 2500/µL.
  3. Lymphocyte count ≥ 500/µL.
  4. Serum albumin ≥ 2.5 g/dL.
  5. Platelet count ≥ 100,000/µL without transfusion (without transfusion within 2 weeks of laboratory test used to determine eligibility).
  6. Hemoglobin ≥ 9.0 g/dL, participants may be transfused or receive erythropoietic treatment to meet this criterion.
  7. 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.
  8. 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.
  9. Serum bilirubin ≤ 1.5 × ULN. Participants with known Gilbert's syndrome who have serum bilirubin level ≤ 3 × ULN may be enrolled.
  10. Serum creatinine ≤ 1.5 × ULN.

• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than 1% (one percent) per year during the treatment period and for at least 5 months after the last dose of atezolizumab.

• For men: agreement to remain abstinent (refrain from heterosexual intercourse with a female partner of childbearing potential or who is pregnant) or use contraceptive measures that result in a failure rate of less than 1% (one percent) per year, and agreement to refrain from donating sperm, during the treatment period and for at least 5 months after the last dose of atezolizumab.

• Asymptomatic participants with treated or untreated CNS lesions are eligible provided that all of the following criteria are met:

  1. Measurable disease, per RECIST 1.1, must be present.
  2. The participant has no history of intracranial hemorrhage or spinal cord hemorrhage.
  3. The participant has not undergone stereotactic radiotherapy within 7 days prior to the initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment.
  4. The participant has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted.

• Ability to give informed consent for the study procedures defined in this protocol.

Exclusion Criteria

• 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:

  1. 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.
  2. Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone may be eligible for this study.
  3. 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:

  1. Rash must cover less than 10% (ten percent) of body surface area (BSA).
  2. Disease is well controlled at baseline and only requiring low potency topical steroids.
  3. 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).

• Participants with hepatitis B virus (HBV) are excluded if one of the following conditions is met:

  1. Positive hepatitis B surface antigen (HBsAg) test at screening; or
  2. Negative or positive hepatitis B surface antibody (HBsAb) test at screening accompanied by a positive total hepatitis B core antibody (HBcAb) test followed by a positive (per local laboratory definition) HBV DNA test.

• Positive hepatitis C virus (HCV) antibody test followed by a positive HCV RNA test at screening.

• Active tuberculosis.

• Severe infections within 2 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.

• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina.

• Major surgical procedure within 21 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study.

• Prior allogeneic stem cell or solid organ transplant.

• Treatment with systemic immunostimulatory agents (including but not limited to interferons, interleukin-2 (IL-2)) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1.

• Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumour necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial.

• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab.

• Participants who are otherwise felt by the treating clinician to be unfit to proceed with this protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Breast Cohort	Atezolizumab	Cohort of participants whose primary tumour type is breast.
Lung Cohort	Atezolizumab	Cohort of participants whose primary tumour type is lung.
GI Cohort	Atezolizumab	Cohort of participants whose primary tumour type is gastrointestinal (including pancreas and hepatobiliary).
Sarcoma Cohort	Atezolizumab	Cohort of participants whose primary tumour type is sarcoma.
Gyne Cohort	Atezolizumab	Cohort of participants whose primary tumour type is gynecological.
GU Cohort	Atezolizumab	Cohort of participants whose primary tumour type is genitourinary.
Primary Unknown Cohort	Atezolizumab	Cohort of participants whose primary tumour type is unknown.
Other Cohort	Atezolizumab	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.

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR) in each tumour-defined cohort, 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.	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.

Secondary Outcome Measures

Name	Time	Method
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.	The length of time from the initiation of atezolizumab that participants in each tumour-defined cohort survive.
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.	The length of time from the first dose of atezolizumab until participants in each tumour-defined cohort have progressive disease (PD), as defined by RECIST 1.1.
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.	The length of time from the first response to treatment (CR or PR) until participants in each tumour-defined cohort have progressive disease (PD), as defined by RECIST 1.1.
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.	The percentage of participants in each tumour-defined cohort who have a complete response (CR), partial response (PR), or stable disease (SD) response to treatment, as defined by RECIST 1.1, at the 18-week follow-up scan.
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.	Survival time (from the initiation of atezolizumab) multiplied by quality of life. Participants' responses to health-related quality of life questions on the EQ-5D-3L questionnaire will be converted to utility weights using existing conversion scales that are based on patient and public valuations of the health states described by the EQ-5D-3L questionnaire.

Trial Locations

Locations (2)

BC Cancer; 🇨🇦 Vancouver, British Columbia, Canada

University Health Network / Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada