A Phase II Study of Atezolizumab and Tiragolumab in Patients With NSCLC or Advanced Solid Tumors Who Have Had Prior Treatment With a PD-1 Inhibitor
Overview
- Phase
- Phase 2
- Intervention
- Atezolizumab
- Conditions
- Non-Small Cell Lung Cancer
- Sponsor
- SCRI Development Innovations, LLC
- Enrollment
- 46
- Locations
- 7
- Primary Endpoint
- Overall Response Rate
- Status
- Completed
- Last Updated
- 8 months ago
Overview
Brief Summary
This is a Phase II, two part trial (A and B), open label study of Atezolizumab and tiragolumab, or atezolizumab combined with SOC chemotherapy in patients with NSCLC or advanced solid tumors that have had prior treatment with a PD-1 inhibitor (e.g. nivolumab or pembrolizumab).
Detailed Description
Arm A consists of approximately 20 patients with advanced NSCLC who received first-line anti-PD-1 therapy, who have subsequent disease progression. Arm B consists of approximately 15 patients per disease type (renal cell carcinoma \[RCC\] progressing on prior anti-PD-1 therapy, triple negative breast cancer \[TNBC\] progressing on prior anti-PD-1 therapy, NSCLC progressing on check-point inhibitors plus chemotherapy in the first-line setting; and microsatellite instability-high \[MSI-high\] solid tumors \[as determined by local testing for MSI/mismatch repair (MMR)\] progressing on prior anti-PD-1 therapy).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 - 2
- •Adequate hematologic function defined as:
- •\- Absolute neutrophil count (ANC) ≥1500/μL with one exception: Patients with benign ethnic neutropenia (BEN): ANC \>1300/ μL
- •\- Lymphocyte count ≥0.5 × 109/L (500/µL)
- •Hemoglobin (Hgb) ≥9 g/dL (patients may be transfused to meet this criterion)
- •Platelets ≥100,000/µL (without transfusion, within 7 days of enrollment)
- •Adequate liver function defined as:
- •\- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the upper limit of normal (ULN)
- •\- Total bilirubin ≤1.5 x ULN (patients with known Gilbert syndrome: serum bilirubin level ≤ 3 x ULN)
- •Adequate renal function defined as serum creatinine ≤1.5 mg/dL (133 μmol/L) or calculated creatinine clearance ≥30 mL/min as calculated by the Cockcroft Gault formula
Exclusion Criteria
- •History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
- •History of any Grade 3 or 4 toxicities to a prior CPI treatment
- •Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulations
- •Most recent immunotherapy ≤21 days and ≥ Grade 2 immunotherapy-related side effects, with the exception of alopecia.
- •Use of systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) ≤28 days or 5 half-lives (whichever is shorter) prior to the first dose of study drugs.
- •Treatment with chemotherapy in the first line setting.
- •Treatment with investigational therapy within 28 days prior to initiation of study treatment.
- •8\. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF- agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study, with the following exceptions:
- •Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.
- •Patients who received mineralocorticoids (e.g., fludrocortisone), inhaled corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
Arms & Interventions
Arm A1 (NSCLC Chemo + Atezolizumab)
Arm A NSCLC participants randomized to receive chemotherapy plus atezolizumab at a flat dose of 1200 mg intravenously (IV) every 3 weeks. Standard of care chemotherapy is defined as a platinum-doublet therapy (or triplet if bevacizumab is used) of the Investigator's choice.
Intervention: Atezolizumab
Arm A1 (NSCLC Chemo + Atezolizumab)
Arm A NSCLC participants randomized to receive chemotherapy plus atezolizumab at a flat dose of 1200 mg intravenously (IV) every 3 weeks. Standard of care chemotherapy is defined as a platinum-doublet therapy (or triplet if bevacizumab is used) of the Investigator's choice.
Intervention: Standard of Care Chemotherapy
Arm B (Atezolizumab only)
In Arm B, non-randomized participants with specific advanced solid tumors will be treated with atezolizumab at a flat dose of 1200 mg IV every 3 weeks until progression or unacceptable toxicity.
Intervention: Atezolizumab
Arm A2 (NSCLC Standard of Care Chemo)
Arm A NSCLC participants randomized to receive platinum-based standard of care doublet chemotherapy (or triplet if bevacizumab is used) will be given by IV every 3 weeks. Platinum chemotherapy may be cisplatin or carboplatin chosen based on histology and at the discretion of the treating investigator. Arm A2 closed early due to change in recommended Standard of Care therapies.
Intervention: Standard of Care Chemotherapy
Arm B (Atezolizumab and Tiragolumab)
In Arm B, non-randomized participants with specific advanced solid tumors will be treated with atezolizumab at a flat dose of 1200 mg IV and tiragolumab at a flat dose of 600mg IVevery 3 weeks until progression or unacceptable toxicity. The addition of tiragolumab was a later update to protocol. No randomization into or within Arm B.
Intervention: Atezolizumab
Arm B (Atezolizumab and Tiragolumab)
In Arm B, non-randomized participants with specific advanced solid tumors will be treated with atezolizumab at a flat dose of 1200 mg IV and tiragolumab at a flat dose of 600mg IVevery 3 weeks until progression or unacceptable toxicity. The addition of tiragolumab was a later update to protocol. No randomization into or within Arm B.
Intervention: Tiragolumab
Outcomes
Primary Outcomes
Overall Response Rate
Time Frame: Every 8 weeks until tumor progression or treatment discontinuation, up to 52 months.
Overall Response Rate (ORR) is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) out of all treated participants. Confirmed response is two consecutive CR or PR at least 4 weeks apart according to the immune-modified RECIST criteria. CR=disappearance of all target and non-target lesions. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of lesion diameters.
Secondary Outcomes
- Incidence of Treatment-emergent Adverse Events (AEs) as a Measure of Safety(Every 3 weeks, up to 52 months)
- Disease Control Rate (DCR)(Every 8 weeks until tumor progression or treatment discontinuation, up to 52 months.)