Study of Novel Treatment Combinations in Patients With Lung Cancer
- Conditions
- Lung CancerResectable Non-Small-Cell Lung CancerAdvanced or Metastatic Non-Small-Cell Lung Cancer
- Interventions
- Drug: Domvanalimab (DOM)Drug: Sacituzumab govitecan-hziy (SG)
- Registration Number
- NCT05633667
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 593
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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG) + Domvanalimab (DOM) Zimberelimab (ZIM) Participants will receive ZIM, SG and DOM until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 03 - ZIM + DOM + Platinum-based Chemotherapy Zimberelimab (ZIM) 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). Substudy 03 - ZIM + Platinum-based Chemotherapy Zimberelimab (ZIM) 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). Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG) + Domvanalimab (DOM) Domvanalimab (DOM) Participants will receive ZIM, SG and DOM until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 01: ZIM + Platinum Based Chemotherapy Zimberelimab (ZIM) 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). Substudy 01: ZIM + Platinum Based Chemotherapy Pemetrexed 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). Substudy 03 - ZIM + Platinum-based Chemotherapy Carboplatin 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). Substudy 01: ZIM + DOM + Etrumadenant (ETRUMA) Zimberelimab (ZIM) Participants will receive ZIM, DOM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 01: ZIM + Platinum Based Chemotherapy Nab-paclitaxel 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). Substudy 02: SG + ZIM + ETRUMA Sacituzumab govitecan-hziy (SG) Participants will receive SG, ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 02: SG + ZIM + ETRUMA Etrumadenant (ETRUMA) Participants will receive SG, ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 03 - ZIM + DOM + Platinum-based Chemotherapy Domvanalimab (DOM) 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). Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG) + Domvanalimab (DOM) Sacituzumab govitecan-hziy (SG) Participants will receive ZIM, SG and DOM until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 01: ZIM + DOM + Etrumadenant (ETRUMA) Domvanalimab (DOM) Participants will receive ZIM, DOM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 01: ZIM + DOM + Etrumadenant (ETRUMA) Etrumadenant (ETRUMA) Participants will receive ZIM, DOM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 03 - ZIM + DOM + Platinum-based Chemotherapy Pemetrexed 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). Substudy 01: ZIM + ETRUMA Zimberelimab (ZIM) Participants will receive ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 01: ZIM + ETRUMA Etrumadenant (ETRUMA) Participants will receive ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG) Zimberelimab (ZIM) Participants will receive ZIM and SG until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 01: ZIM + Platinum Based Chemotherapy Carboplatin 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). Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG) Sacituzumab govitecan-hziy (SG) Participants will receive ZIM and SG until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 02: SG + ZIM + ETRUMA Zimberelimab (ZIM) Participants will receive SG, ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 03 - ZIM + DOM + Platinum-based Chemotherapy Paclitaxel 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). Substudy 02: Either Docetaxel or SG (Monotherapy Only) Sacituzumab govitecan-hziy (SG) Participants will receive either Docetaxel or SG until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 03 - ZIM + DOM + Platinum-based Chemotherapy Carboplatin 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). Substudy 03: Nivolumab + Platinum-based Chemotherapy Carboplatin 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). Substudy 01: ZIM + Platinum Based Chemotherapy Cisplatin 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). Substudy 01: ZIM + Platinum Based Chemotherapy Paclitaxel 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). Substudy 02: Either Docetaxel or SG (Monotherapy Only) Docetaxel Participants will receive either Docetaxel or SG until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met. Substudy 03 - ZIM + Platinum-based Chemotherapy Pemetrexed 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). Substudy 03 - ZIM + Platinum-based Chemotherapy Paclitaxel 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). Substudy 03: Nivolumab + Platinum-based Chemotherapy Pemetrexed 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). Substudy 03: Nivolumab + Platinum-based Chemotherapy Paclitaxel 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). Substudy 03: Nivolumab + Platinum-based Chemotherapy Nivolumab 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).
- Primary Outcome Measures
Name Time Method 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 Up to 5 years 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.
Substudy 03: Complete Pathological Response (pCR) Rate Up to 5 years 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.
- Secondary Outcome Measures
Name Time Method 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 Substudies 01 and 02: Progression-free Survival (PFS) According to RECIST Version 1.1 Up to 5 years PFS is defined as the time from the date of randomization until disease progression (PD) or death, whichever comes first.
Substudies 01 and 02: Duration of response (DOR) According to RECIST Version 1.1 Up to 5 years DOR is defined as the time from the first response (CR or PR) until the first documented PD, or death, whichever comes first.
All Substudies: Overall survival (OS) Up to 5 years OS is defined as the time from the date of randomization until death from any cause.
Substudy 03: Event-Free Survival (EFS) Up to 5 years 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.
Substudy 03: Major Pathological Response (MPR) Rate Up to 5 years 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.
Trial Locations
- Locations (87)
St. Bartholomew's Hospital,Substudy-01
🇬🇧London, United Kingdom
St. Bartholomew's Hospital,Substudy-02
🇬🇧London, United Kingdom
St. Bartholomew's Hospital,Substudy-03
🇬🇧London, United Kingdom
Arizona Oncology Associates,Substudy-01
🇺🇸Tucson, Arizona, United States
Arizona Oncology Associates,Substudy-02
🇺🇸Tucson, Arizona, United States
Rocky Mountain Cancer Center,Substudy-01
🇺🇸Denver, Colorado, United States
Rocky Mountain Cancer Center,Substudy-02
🇺🇸Denver, Colorado, United States
Fort Wayne Medical Oncology and Hematology, Inc.,Substudy-03
🇺🇸Fort Wayne, Indiana, United States
Baptist Health Lexington,Substudy-03
🇺🇸Lexington, Kentucky, United States
Oncology Associates of Oregon, PC,Substudy-02
🇺🇸Eugene, Oregon, United States
Texas Oncology - Central South,Substudy-01
🇺🇸Austin, Texas, United States
Texas Oncology - Central South,Substudy-02
🇺🇸Austin, Texas, United States
US Oncology Investigational Products Center (IPC),Substudy-01
🇺🇸Fairfax, Virginia, United States
US Oncology Investigational Products Center (IPC),Substudy-02
🇺🇸Fairfax, Virginia, United States
Fred Hutchinson Cancer Center,Substudy-01
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Center,Substudy-02
🇺🇸Seattle, Washington, United States
Centro Gaúcho Integrado de Oncologia Hematologia, Ensino e Pesquisa Ltda./Hospital Mãe de Deus,Substudy-03
🇧🇷Porto Alegre, Brazil
Hospital Mae de Deus
🇧🇷Porto Alegre, Brazil
Hospital Sao Lucas da PUC Rio Grande do Sul,Substudy-03
🇧🇷Porto Alegre, Brazil
Fundação Antonio Prudente/A.C. Camargo Cancer Center,Substudy-03
🇧🇷São Paulo, Brazil
Real e Benemérita Associação Portuguesa de Beneficência/Hospital Beneficência Portuguesa de São Paulo (Hospital BP),Substudy-03
🇧🇷São Paulo, Brazil
Queen Mary Hospital,Substudy-01
🇭🇰Hong Kong, Hong Kong
Queen Mary Hospital,Substudy-02
🇭🇰Hong Kong, Hong Kong
Queen Elizabeth Hospital,Substudy-01
🇭🇰Hong Kong, Hong Kong
Rambam Health Care Campus,Substudy-03
🇮🇱Haifa, Israel
Shaare Zedek Medical Center,Substudy-01
🇮🇱Jerusalem, Israel
Shaare Zedek Medical Center,Substudy-02
🇮🇱Jerusalem, Israel
Shaare Zedek Medical Center,Substudy-03
🇮🇱Jerusalem, Israel
Hadassah University Medical Center,Substudy-03
🇮🇱Jerusalem, Israel
Rabin Medical Center,Substudy-03
🇮🇱Petah Tiqva, Israel
Tel Aviv Sourasky Medical Center,Substudy-01
🇮🇱Tel Aviv-Yafo, Israel
Tel Aviv Sourasky Medical Center,Substudy-02
🇮🇱Tel Aviv-Yafo, Israel
Tel-Aviv Sourasky Medical Center,Substudy-03
🇮🇱Tel Aviv-Yafo, Israel
Chungbuk National University Hospital,Substudy-01
🇰🇷Cheongju-si, Korea, Republic of
Chungbuk National University Hospital,Substudy-02
🇰🇷Cheongju-si, Korea, Republic of
National Cancer Center,Substudy-01
🇰🇷Goyang, Korea, Republic of
National Cancer Center,Substudy-02
🇰🇷Goyang, Korea, Republic of
National Cancer Center,Substudy-03
🇰🇷Goyang, Korea, Republic of
Asan Medical Centre,Substudy-01
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center,Substudy-01
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center,Substudy-02
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center,Substudy-03
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System,Substudy-01
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System,Substudy-02
🇰🇷Seoul, Korea, Republic of
Seoul National University,Substudy-01
🇰🇷Seoul, Korea, Republic of
Seoul National University,Substudy-02
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital,Substudy-01
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital,Substudy-03
🇰🇷Seoul, Korea, Republic of
Changhua Christian Hospital,Substudy-01
🇨🇳Changhua City, Taiwan
Changhua Christian Hospital,Substudy-02
🇨🇳Changhua City, Taiwan
Changhua Christian Hospital,Substudy-03
🇨🇳Changhua City, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital,Substudy-01
🇨🇳Kaohsiung City, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital,Substudy-02
🇨🇳Kaohsiung City, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital,Substudy-03
🇨🇳Kaohsiung City, Taiwan
Kaohsiung Chang Gung Memorial Hospital,Substudy-01
🇨🇳Kaohsiung, Taiwan
Kaohsiung Chang Gung Memorial Hospital,Substudy-02
🇨🇳Kaohsiung, Taiwan
Kaohsiung Chang Gung Memorial Hospital,Substudy-03
🇨🇳Kaohsiung, Taiwan
National Taiwan University Hospital,Substudy-01
🇨🇳Taipei City, Taiwan
National Taiwan University Hospital,Substudy-02
🇨🇳Taipei City, Taiwan
Memorial Ankara Hospital,Substudy-03
🇹🇷Ankara, Turkey
St James University Hospital,,Substudy-01
🇬🇧Leeds, United Kingdom
Washington University School of Medicine - Siteman Cancer Center,Substudy-01
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine - Siteman Cancer Center,Substudy-02
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine - Siteman Cancer Center,Substudy-03
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine - Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Oncology Hematology Care Clinical Trials, LLC,Substudy-01
🇺🇸Cincinnati, Ohio, United States
Oncology Hematology Care Clinical Trials, LLC,Substudy-02
🇺🇸Cincinnati, Ohio, United States
Oncology Associates of Oregon, PC,Substudy-01
🇺🇸Eugene, Oregon, United States
Queen Elizabeth Hospital,Substudy-02
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hospital,Substudy-01
🇭🇰New Territories, Hong Kong
Prince of Wales Hospital,Substudy-02
🇭🇰New Territories, Hong Kong
Rambam Health Care Campus,Substudy-01
🇮🇱Haifa, Israel
Rambam Health Care Campus,Substudy-02
🇮🇱Haifa, Israel
Chonnam National University Hwasun Hospital,Substudy-01
🇰🇷Gwangju, Korea, Republic of
Chonnam National University Hwasun Hospital,Substudy-03
🇰🇷Gwangju, Korea, Republic of
Seoul National University Bundang Hospital,Substudy-01
🇰🇷Gyeonggi-do, Korea, Republic of
Seoul National University Bundang Hospital,Substudy-03
🇰🇷Gyeonggi-do, Korea, Republic of
Kosin University Gospel Hospital,Substudy-01
🇰🇷Seo-gu, Korea, Republic of
Kosin University Gospel Hospital,Substudy-03
🇰🇷Seo-gu, Korea, Republic of
Severance Hospital, Yonsei University Health System,Substudy-03
🇰🇷Seoul, Korea, Republic of
Asan Medical Center,Substudy-02
🇰🇷Seoul, Korea, Republic of
Asan Medical Center,Substudy-03
🇰🇷Seoul, Korea, Republic of
Dicle University Medical Faculty,Substudy-03
🇹🇷Diyarbakir, Turkey
Necmettin Erbakan Universitesi,Substudy-03
🇹🇷Meram Konya, Turkey
Birmingham Heartlands Hospital,Substudy-03
🇬🇧Birmingham, United Kingdom
University Hospitals Birmingham NHS Trust,Substudy-01
🇬🇧Birmingham, United Kingdom
University Hospitals Birmingham NHS Trust,Substudy-02
🇬🇧Birmingham, United Kingdom