Study With Immunotherapy Combinations in Participants With Metastatic Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is to assess the objective response rate (ORR) of immunotherapy-based combination therapy and to assess the safety and tolerability of immunotherapy-based combination therapy.

Official Title
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A Phase II, Open-label, Platform Study, to Evaluate Immunotherapy-based Combinations in Participants With Advanced Non-Small Cell Lung Cancer

Conditions
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Advanced Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Domvanalimab
* Drug: Quemliclustat
* Drug: Zimberelimab
* Drug: Docetaxel
* Drug: Platinum-Based Doublet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed, documented diagnosis of Stage IV metastatic, NSCLC Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1 At least one measurable target lesion per RECIST v1.1. Adequate organ and marrow function Participants must be willing to provide adequate tumor tissue Exclusion Criteria: Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of Investigational Product(s) (IPs) hazardous Use of any live vaccines against infectious diseases within 28 days of first dose of IP(s). Concurrent chronic medical condition requiring the use of supra-physiologic doses of corticosteroids (> 10 mg/day of oral prednisone or equivalent) or immunosuppressive medications (absorbable topical corticosteroids are not excluded). Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1: Domvanalimab + Zimberelimab<br>Domvanalimab and Zimberelimab, both administered by IV infusion | Drug: Domvanalimab<br>* Administered as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered as specified in the treatment arm<br>|
| Experimental: A2: Domvanalimab + Zimberelimab<br>Domvanalimab and Zimberelimab, both administered by IV infusion | Drug: Domvanalimab<br>* Administered as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered as specified in the treatment arm<br>|
| Experimental: A3: Quemliclustat + Zimberelimab<br>Quemliclustat and Zimberelimab, both administered by IV infusion | Drug: Quemliclustat<br>* Administered as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered as specified in the treatment arm<br>|
| Experimental: B1: Quemliclustat + Zimberelimab + Platinum Doublet Chemotherapy<br>Quemliclustat, zimberelimab, and platinum doublet chemotherapy, all administered by IV infusion | Drug: Quemliclustat<br>* Administered as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered as specified in the treatment arm<br>Drug: Platinum-Based Doublet<br>* Administered as specified in the treatment arm<br>|
| Experimental: B2: Domvanalimab + Zimberelimab + Platinum Doublet Chemotherapy<br>Domvanalimab, Zimberelimab, and platinum doublet chemotherapy, all administered by IV infusion | Drug: Domvanalimab<br>* Administered as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered as specified in the treatment arm<br>Drug: Platinum-Based Doublet<br>* Administered as specified in the treatment arm<br>|
| Experimental: B3: Domvanalimab + Quemliclustat + Zimberelimab + Platinum Doublet Chemotherapy<br>Domvanalimab, Quemliclustat, Zimberelimab, and platinum doublet chemotherapy, all administered by IV infusion | Drug: Domvanalimab<br>* Administered as specified in the treatment arm<br>Drug: Quemliclustat<br>* Administered as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered as specified in the treatment arm<br>Drug: Platinum-Based Doublet<br>* Administered as specified in the treatment arm<br>|
| Experimental: C1: Quemliclustat + Zimberelimab + Docetaxel<br>Quemliclustat, Zimberelimab, and Docetaxel, all administered by IV infusion | Drug: Quemliclustat<br>* Administered as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered as specified in the treatment arm<br>Drug: Docetaxel<br>* Administered as specified in the treatment arm<br>|
| Experimental: C2: Domvanalimab + Zimberelimab + Docetaxel<br>Domvanalimab, Zimberelimab, and Docetaxel, all administered by IV infusion | Drug: Domvanalimab<br>* Administered as specified in the treatment arm<br>Drug: Quemliclustat<br>* Administered as specified in the treatment arm<br>Drug: Docetaxel<br>* Administered as specified in the treatment arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) |  | Up to 58 months | 
| The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) |  | Up to 58 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | From date of first dose until the date of death due to any cause (approximately 58 months) | 
| Progression-free Survival (PFS) as determined by the Investigator according to RECIST v1.1 |  | Up to 58 months | 
| Disease Control Rate (DCR) |  | Up to 58 months | 
| Duration of response (DoR) as determined by the Investigator according to RECIST v1.1 |  | Up to 58 months | 
| Investigational study treatments peak plasma or serum concentration (Cmax) |  | Up to 58 months | 
| Investigational study treatments time of peak concentration (Tmax) |  | Up to 58 months | 
| Investigational study treatments area under the plasma or serum concentration versus time curve (AUC) |  | Up to 58 months | 
| Percentage of biologic treatment-emergent antidrug-antibody (ADA)-positive participants and ADA-negative participants |  | Up to 58 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Non-Small Cell Lung Cancer, Domvanalimab, Zimberelimab, Quemliclustat, Anti-TIGIT antibody, Anti-PD-1 antibody