A Phase Ib Study of The Safety And Pharmacology of Atezolizumab (Anti-Pd-L1 Antibody) Administered With Ipilimumab, Interferon-Alpha, or Other Immune-Modulating Therapies in Patients With Locally Advanced or Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Atezolizumab
- Conditions
- Solid Cancers
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 158
- Locations
- 9
- Primary Endpoint
- Recommended Phase II Dose (RP2D) of Atezolizumab When Given in Combination With Ipilimumab and Interferon Alfa-2b
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This global, multicenter, open-label study will evaluate the safety and tolerability of atezolizumab in combination with other immune-modulating therapies in the treatment of selected advanced or metastatic malignancies. The atezolizumab plus ipilimumab arm (Arm A) will focus primarily on participants with advanced or metastatic non-small cell lung cancer (NSCLC). The atezolizumab plus interferon alfa-2b arm (Arm B), plus pegylated interferon alfa-2a (PEG-interferon alfa-2a, Arm C), and atezolizumab plus PEG-interferon Alfa-2a plus bevacizumab (Arm D) will enroll participants with advanced or metastatic renal cell carcinoma (RCC), metastatic NSCLC and melanoma. The atezolizumab plus obinutuzumab) (Arm E) will enroll participants with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Atezolizumab will be administered as intravenous (IV) infusion every 3 weeks (q3w).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically documented locally advanced or metastatic solid tumors meeting the following study drug-specific criteria:
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- •Life expectancy greater than or equal to (\>/=) 12 weeks
- •Measurable disease, as defined by RECIST v1.1
- •Adequate hematologic and end organ function as confirmed by laboratory results within 14 days prior to the first study treatment
- •Inclusion criteria specific to Arm A: Atezolizumab+ Ipilimumab
- •Escalation stage: NSCLC participants
- •Mandatory biopsy cohort: NSCLC or melanoma atezolizumab
- •Prior atezolizumab-treated cohort: participants with NSCLC or melanoma previously treated with atezolizumab
- •Inclusion criteria specific to Arm B: Atezolizumab+ Interferon alfa-2b
Exclusion Criteria
- •General Medical Exclusions:
- •Pregnant and lactating women
- •Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment, with the following exception: (1) hormone-replacement therapy or oral contraceptives; (2) tyrosine kinase inhibitors (TKIs) that have been discontinued greater than (\>) 7 days prior to Cycle 1, Day 1, baseline scans must be obtained after discontinuation of prior TKIs
- •Investigational therapy within 28 days prior to initiation of study treatment
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- •Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of the atezolizumab formulation
- •History of or active autoimmune disease
- •History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, risk of pulmonary toxicity, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- •Prior allogeneic bone marrow transplantation or prior solid organ transplantation
- •History of human immunodeficiency virus (HIV)
Arms & Interventions
Arm A: Atezolizumab with Ipilimumab
Participants will receive atezolizumab along with ipilimumab.
Intervention: Atezolizumab
Arm A: Atezolizumab with Ipilimumab
Participants will receive atezolizumab along with ipilimumab.
Intervention: Ipilimumab
Arm B: Atezolizumab with Interferon alfa-2b
Participants will receive atezolizumab along with Interferon alfa-2b.
Intervention: Atezolizumab
Arm B: Atezolizumab with Interferon alfa-2b
Participants will receive atezolizumab along with Interferon alfa-2b.
Intervention: Interferon alfa-2b
Arm C: Atezolizumab with PEG- interferon alfa-2a
Participants will receive atezolizumab along with PEG- interferon alfa-2a.
Intervention: Atezolizumab
Arm C: Atezolizumab with PEG- interferon alfa-2a
Participants will receive atezolizumab along with PEG- interferon alfa-2a.
Intervention: PEG-interferon alfa-2a
Arm D:Atezolizumab with PEG-interferon alfa-2a and Bevacizumab
Participants will receive atezolizumab along with PEG- interferon alfa-2a and bevacizumab.
Intervention: Atezolizumab
Arm D:Atezolizumab with PEG-interferon alfa-2a and Bevacizumab
Participants will receive atezolizumab along with PEG- interferon alfa-2a and bevacizumab.
Intervention: Bevacizumab
Arm D:Atezolizumab with PEG-interferon alfa-2a and Bevacizumab
Participants will receive atezolizumab along with PEG- interferon alfa-2a and bevacizumab.
Intervention: PEG-interferon alfa-2a
Arm E: Atezolizumab with Obinutuzumab
Participants will receive atezolizumab along with obinutuzumab or atezolizumab alone.
Intervention: Atezolizumab
Arm E: Atezolizumab with Obinutuzumab
Participants will receive atezolizumab along with obinutuzumab or atezolizumab alone.
Intervention: Obinutuzumab
Outcomes
Primary Outcomes
Recommended Phase II Dose (RP2D) of Atezolizumab When Given in Combination With Ipilimumab and Interferon Alfa-2b
Time Frame: From the first atezolizumab treatment up to 21 days
Percentage of Participants with Adverse Events
Time Frame: From the first atezolizumab treatment up to 4.5 years (yr)
Secondary Outcomes
- Progression-Free Survival(Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]))
- Percentage of Participants with Best Overall Response, as Assessed Using Immune Modified RECIST Criteria(Screening to progression or death, up to 4.5 years (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]))
- Serum Obinutuzumab Concentration(Baseline up to 4.5 years (detailed outcome given in outcome description))
- Anti-Drug Antibody to Atezolizumab(Baseline up to 4.5 years (detailed timeframe is given in outcome description))
- Anti-Drug Antibody to Ipilimumab(Baseline up to 4.5 years (detailed timeframe is given in outcome description))
- Anti-Drug Antibody to Bevacizumab(Baseline up to 4.5 years (detailed timeframe is given in outcome description))
- Anti-Drug Antibody to Obinutuzumab(Baseline up to 4.5 years (detailed timeframe is given in outcome description))
- Percentage of Participants with Best Overall Response, as Assessed Using Conventional Response Evaluation Criteria in Solid Tumors (RECIST) v1.1(Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]))
- Serum Atezolizumab Concentration(Baseline up to 4.5 years (detailed timeframe is given in outcome description))
- Serum Ipilimumab Concentration(Baseline up to 4.5 years (detailed timeframe is given in outcome description))
- Duration of Objective Response(Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]))
- Percentage of Participants with Objective Response, as Assessed Using Immune Modified RECIST Criteria(Screening to progression or death, up to 4.5 yr (assessed at Baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]))
- Overall Survival(Baseline to death (up to 4.5 yr))
- Percentage of Participants with Objective Response, as Assessed Using Conventional RECIST v1.1(Screening to progression or death, up to 4.5 yr (assessed at Baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]))
- Serum Bevacizumab Concentration(Baseline up to 4.5 years (detailed timeframe is given in outcome description))