Study of Novel Treatment Combinations in Patients With Lung Cancer

Study Overview
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Brief Summary
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The goal of this platform clinical trial is to test how well novel treatment combinations work in participants with lung cancer. Substudy-01 will compare the different novel combinations versus standard of care in participants with metastatic (cancer that has spread) non-small-cell lung cancer (NSCLC) who have have not been treated before. Substudy-02 will compare the different novel combination versus standard of care in participants with cancer that has progressed after receiving previous treatment for metastatic NSCLC. Substudy-03 will compare the different novel combinations versus standard of care in participants with resectable stage II-III NSCLC. The primary objectives of this study are: Substudy-01 and Substudy-02: To evaluate the objective response rate (ORR) assessed per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Substudy-03: To evaluate the efficacy of treatment combinations based on complete pathological response (pCR) rate.

Official Title
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A Phase 2 Platform Study Evaluating the Safety and Efficacy of Novel Treatment Combinations in Patients With Lung Cancer (VELOCITY-Lung)

Conditions
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Lung Cancer, Advanced or Metastatic Non-Small-Cell Lung Cancer, Resectable Non-Small-Cell Lung Cancer

Intervention / Treatment
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* Drug: Zimberelimab (ZIM)
* Drug: Domvanalimab (DOM)
* Drug: Sacituzumab govitecan-hziy (SG)
* Drug: Etrumadenant (ETRUMA)
* Drug: Carboplatin
* Drug: Cisplatin
* Drug: Pemetrexed
* Drug: Paclitaxel
* Drug: Nab-paclitaxel
* Drug: Docetaxel
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: All Substudies: Histologically or cytologically documented non-small-cell lung cancer (NSCLC). No known actionable genomic alterations for which targeted therapies are available. Eastern cooperative oncology group (ECOG) performance status score of 0 or 1. Measurable disease per response evaluation criteria in solid tumors. Adequate hematologic and end-organ function. Individuals of childbearing potential who engage in heterosexual intercourse must agree to use specified method(s) of contraception. Substudy 01: All Experimental arms Stage IV NSCLC. For individuals with nonsquamous histology: Epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alteration negative. PD-L1 status by central confirmation. No prior systemic treatment for metastatic NSCLC. Substudy 02: All Experimental arms Stage IV NSCLC. In individuals with nonsquamous histology and actionable EGFR, ALK, or other known genomic alterations must have received treatment with at least 1 targeted therapy to the appropriate genomic alteration. Substudy 03: All Experimental arms Previously untreated individuals with resectable (Stage II, IIIA, IIIB (T[3-4]N2) NSCLC (per American Joint Committee on Cancer (AJCC) Edition 8). Planned surgery must comprise of lobectomy, sleeve lobectomy, or bi-lobectomy. PD-L1 status by central confirmation. For individuals with nonsquamous histology: Epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alteration negative. Key Exclusion Criteria: All Substudies: Mixed small-cell lung cancer and NSCLC histology. Active second malignancy. Active autoimmune disease. History of or current non-infectious pneumonitis/interstitial lung disease. Active serious infection within 4 weeks prior to study treatment. Substudy 01 and 02 Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Received previous anticancer therapy within 4 weeks prior to enrollment. Substudy 03: All Experimental arms NSCLC previously treated with systemic therapy or radiotherapy. Received prior treatment with any anti-PD-(L)-1 or other immune checkpoint inhibitors (CPIs). 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG) + Domvanalimab (DOM)<br>Participants will receive ZIM, SG and DOM until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met. | Drug: Zimberelimab (ZIM)<br>* Administered intravenously<br>* Other names: GS-0122;Drug: Domvanalimab (DOM)<br>* Administered intravenously<br>* Other names: GS-0154;Drug: Sacituzumab govitecan-hziy (SG)<br>* Administered intravenously<br>* Other names: IMMU-132;|
| Experimental: Substudy 01: ZIM + DOM + Etrumadenant (ETRUMA)<br>Participants will receive ZIM, DOM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met. | Drug: Zimberelimab (ZIM)<br>* Administered intravenously<br>* Other names: GS-0122;Drug: Domvanalimab (DOM)<br>* Administered intravenously<br>* Other names: GS-0154;Drug: Etrumadenant (ETRUMA)<br>* Administered orally<br>* Other names: GS-0928;|
| Experimental: Substudy 01: ZIM + ETRUMA<br>Participants will receive ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met. | Drug: Zimberelimab (ZIM)<br>* Administered intravenously<br>* Other names: GS-0122;Drug: Etrumadenant (ETRUMA)<br>* Administered orally<br>* Other names: GS-0928;|
| Active Comparator: Substudy 01: ZIM + Platinum Based Chemotherapy<br>Expansion Stage Only: Participants will receive ZIM plus any one of the chemotherapy (choice of chemotherapy is dependent on histology). Platinum Based Chemotherapy will be cisplatin or carboplatin and pemetrexed (non-squamous histology) or carboplatin, paclitaxel and nabpaclitaxel (squamous histology). | Drug: Zimberelimab (ZIM)<br>* Administered intravenously<br>* Other names: GS-0122;Drug: Carboplatin<br>* Administered intravenously<br>Drug: Cisplatin<br>* Administered intravenously<br>Drug: Pemetrexed<br>* Administered intravenously<br>Drug: Paclitaxel<br>* Administered intravenously<br>Drug: Nab-paclitaxel<br>* Administered intravenously<br>|
| Experimental: Substudy 02: SG + ZIM + ETRUMA<br>Participants will receive SG, ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met. | Drug: Zimberelimab (ZIM)<br>* Administered intravenously<br>* Other names: GS-0122;Drug: Sacituzumab govitecan-hziy (SG)<br>* Administered intravenously<br>* Other names: IMMU-132;Drug: Etrumadenant (ETRUMA)<br>* Administered orally<br>* Other names: GS-0928;|
| Active Comparator: Substudy 02: Either Docetaxel or SG (Monotherapy Only)<br>Participants will receive either Docetaxel or SG until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met. | Drug: Sacituzumab govitecan-hziy (SG)<br>* Administered intravenously<br>* Other names: IMMU-132;Drug: Docetaxel<br>* Administered intravenously<br>|
| Experimental: Substudy 03 - ZIM + DOM + Platinum-based Chemotherapy<br>Participants will receive ZIM plus DOM and any one of the chemotherapy (choice of chemotherapy is dependent on histology). Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology). | Drug: Zimberelimab (ZIM)<br>* Administered intravenously<br>* Other names: GS-0122;Drug: Domvanalimab (DOM)<br>* Administered intravenously<br>* Other names: GS-0154;Drug: Carboplatin<br>* Administered intravenously<br>Drug: Pemetrexed<br>* Administered intravenously<br>Drug: Paclitaxel<br>* Administered intravenously<br>|
| Experimental: Substudy 03 - ZIM + Platinum-based Chemotherapy<br>Participants will receive ZIM plus any one of the chemotherapy (choice of chemotherapy is dependent on histology). Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology). | Drug: Zimberelimab (ZIM)<br>* Administered intravenously<br>* Other names: GS-0122;Drug: Carboplatin<br>* Administered intravenously<br>Drug: Pemetrexed<br>* Administered intravenously<br>Drug: Paclitaxel<br>* Administered intravenously<br>|
| Active Comparator: Substudy 03: Nivolumab + Platinum-based Chemotherapy<br>Participants will receive nivolumab plus any one of the chemotherapy (choice of chemotherapy is dependent on histology). Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology). | Drug: Carboplatin<br>* Administered intravenously<br>Drug: Pemetrexed<br>* Administered intravenously<br>Drug: Paclitaxel<br>* Administered intravenously<br>Drug: Nivolumab<br>* Administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Substudies 01 and 02: Objective Response Rate (ORR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | ORR is defined as the proportion of participants achieving a complete response (CR) or partial response (PR) as confirmed at least 4 weeks after the first detection of response. | Up to 5 years | 
| Substudy 03: Complete Pathological Response (pCR) Rate | pCR is defined as the percentage of participants having an absence of residual invasive cancer in resected lung specimens and lymph nodes as assessed by local pathology review. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Substudies 01 and 02: Progression-free Survival (PFS) According to RECIST Version 1.1 | PFS is defined as the time from the date of randomization until disease progression (PD) or death, whichever comes first. | Up to 5 years | 
| Substudies 01 and 02: Duration of response (DOR) According to RECIST Version 1.1 | DOR is defined as the time from the first response (CR or PR) until the first documented PD, or death, whichever comes first. | Up to 5 years | 
| All Substudies: Overall survival (OS) | OS is defined as the time from the date of randomization until death from any cause. | Up to 5 years | 
| Substudy 03: Event-Free Survival (EFS) | Event-Free Survival (EFS) is defined as the time from randomization until any of the following events: any progression precluding surgery or preventing completion of surgery, progression or recurrence of disease after surgery (local or distant), as assessed by investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), or death due to any cause, whichever occurs first. Participants who do not undergo surgery for reasons other than progression will be considered to have had an event at progression or at death. | Up to 5 years | 
| Substudy 03: Major Pathological Response (MPR) Rate | MPR rate is defined as the percentage of participants with ≤ 10% residual tumor in lung and lymph nodes at surgery as evaluated by local pathology review. | Up to 5 years | 
| All Substudies: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) and Related TEAEs |  | First dose date up to 24 months plus 100 days | 
| All Substudies: Percentage of Participants Experiencing Clinical Laboratory Abnormalities |  | First dose date up to 24 months plus 100 days |