Study of Novel Treatment Combinations in Patients With Lung Cancer (VELOCITY-Lung)

Gilead Sciences

Status and phase: Enrolling; Phase 2

Conditions: Resectable Non-Small-Cell Lung Cancer; Lung Cancer; Advanced or Metastatic Non-Small-Cell Lung Cancer

Treatments: Drug: Paclitaxel; Drug: Carboplatin; Drug: Domvanalimab (DOM); Drug: Nab-paclitaxel; Drug: Etrumadenant (ETRUMA); Drug: Docetaxel; Drug: Cisplatin; Drug: Nivolumab; Drug: Zimberelimab (ZIM); Drug: Sacituzumab govitecan-hziy (SG); Drug: Pemetrexed

Study type: Interventional

Funder types: Industry

Identifiers

NCT05633667

MOH_2022-12-13_012231 (Registry Identifier)

GS-US-624-6376

Details and patient eligibility

About

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 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.

Enrollment: 593 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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593 participants in 10 patient groups

Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG) + Domvanalimab (DOM)

Experimental group

Description:

Participants will receive ZIM, SG and DOM until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met.

Treatment:

Drug: Sacituzumab govitecan-hziy (SG)

Drug: Zimberelimab (ZIM)

Drug: Domvanalimab (DOM)

Substudy 01: ZIM + DOM + Etrumadenant (ETRUMA)

Experimental group

Description:

Participants will receive ZIM, DOM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.

Treatment:

Drug: Zimberelimab (ZIM)

Drug: Etrumadenant (ETRUMA)

Drug: Domvanalimab (DOM)

Substudy 01: ZIM + ETRUMA

Experimental group

Description:

Participants will receive ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.

Treatment:

Drug: Zimberelimab (ZIM)

Drug: Etrumadenant (ETRUMA)

Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG)

Experimental group

Description:

Participants will receive ZIM and SG until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met.

Treatment:

Drug: Sacituzumab govitecan-hziy (SG)

Drug: Zimberelimab (ZIM)

Substudy 01: ZIM + Platinum Based Chemotherapy

Active Comparator group

Description:

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).

Treatment:

Drug: Pemetrexed

Drug: Zimberelimab (ZIM)

Drug: Cisplatin

Drug: Nab-paclitaxel

Drug: Paclitaxel

Drug: Carboplatin

Substudy 02: SG + ZIM + ETRUMA

Experimental group

Description:

Participants will receive SG, ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.

Treatment:

Drug: Sacituzumab govitecan-hziy (SG)

Drug: Zimberelimab (ZIM)

Drug: Etrumadenant (ETRUMA)

Substudy 02: Either Docetaxel or SG (Monotherapy Only)

Active Comparator group

Description:

Participants will receive either Docetaxel or SG until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.

Treatment:

Drug: Sacituzumab govitecan-hziy (SG)

Drug: Docetaxel

Substudy 03 - ZIM + DOM + Platinum-based Chemotherapy

Experimental group

Description:

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).

Treatment:

Drug: Pemetrexed

Drug: Zimberelimab (ZIM)

Drug: Domvanalimab (DOM)

Drug: Paclitaxel

Drug: Carboplatin

Substudy 03 - ZIM + Platinum-based Chemotherapy

Experimental group

Description:

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).

Treatment:

Drug: Pemetrexed

Drug: Zimberelimab (ZIM)

Drug: Paclitaxel

Drug: Carboplatin

Substudy 03: Nivolumab + Platinum-based Chemotherapy

Active Comparator group

Description:

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).

Treatment:

Drug: Pemetrexed

Drug: Nivolumab

Drug: Paclitaxel

Drug: Carboplatin