A Study of Sotorasib (AMG 510) in Participants With Stage IV NSCLC Whose Tumors Harbor a KRAS p.G12C Mutation in Need of First-line Treatment

Phase 2

Active, not recruiting

• Conditions: Non-small Cell Lung Cancer
• Interventions: Drug: Sotorasib

• Registration Number: NCT04933695
• Lead Sponsor: Amgen

Brief Summary

The main objective of this study is to evaluate the tumor objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in participants who receive sotorasib at either 960 mg daily or 240 mg daily whose tumors are programmed death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) \< 1% and/or harbor a serine/threonine kinase 11 (STK11) co-mutation, in a subgroup of participants with PD-L1 \< 1% and in a subgroup of participants with STK11 co-mutation.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-06-14
• Study First Submitted QC: 2021-06-14
• Study First Posted: 2021-06-22
• Study Start: 2022-01-28
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-02
• Last Update Posted: 2025-05-07
• Primary Completion: 2025-05-30
• Study Completion: 2025-05-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

• Adult (= or > 18 years old) with NSCLC
• Untreated Stage IV metastatic disease. Participants who received adjuvant or neoadjuvant anti-tumor therapy are eligible if the adjuvant/neoadjuvant therapy was completed greater than 12 months prior to the development of metastatic stage IV disease
• Pathologically documented metastatic NSCLC with KRAS G12C mutation (local confirmation)
• Programmed death-ligand 1 (PD-L1) TPS Score < 1% and/or serine/threonine kinase 11 (STK11) co-mutation (local confirmation)
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
• No active brain metastases
• Measurable disease per investigator interpretation using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

Exclusion Criteria

• Mixed small-cell lung cancer and NSCLC histology
• Myocardial Infarction within 6 months of study Day 1
• Use of proton-pump inhibitors (PPIs), histamine (H2) receptor antagonists (H2RA), strong inducers of cytochrome P450 (CYP) 3A4 (CYP3A4) or known CYP3A4 sensitive substrates or P-gp substrates
• Therapeutic or palliative radiation therapy within 2 weeks of study day 1
• Unable to take oral medication
• Unable to receive both iodinated contrast for computed tomography (CT) scans and gadolinium contrast for magnetic resonance imagine (MRI) scans

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sotorasib: 240 mg Daily	Sotorasib	Participants with metastatic non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) p.G12C mutation whose tumors express \< 1% programmed death-ligand 1 (PD-L1) and/or serine/threonine kinase 11 (STK11) mutation in need of first line treatment will be administered sotorasib 240 mg daily. Participants will be stratified by known presence of STK11 mutation.
Sotorasib: 960 mg Daily	Sotorasib	Participants with metastatic non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) p.G12C mutation whose tumors express \< 1% programmed death-ligand 1 (PD-L1) and/or serine/threonine kinase 11 (STK11) mutation in need of first line treatment will be administered sotorasib 960 mg daily. Participants will be stratified by known presence of STK11 mutation.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (OR)	Up to 6 years	OR is defined as the total of Complete Response (CR) and Partial Response (PR).

Secondary Outcome Measures

Name	Time	Method
Number of Participants with a Treatment-emergent Adverse Event (TEAE)	Day 1 up to Month 13
Number of Participants with a Treatment-related Adverse Event	Day 1 up to Month 13
Number of Participants with a Clinically Significant Change from Baseline in Vital Signs	Baseline (Screening; up to 28 days pre-dose) up to Month 13
Disease Control Rate	Up to 6 years
Duration of Reponse (DOR)	Up to 6 years
Time to Response (TTR)	Up to 6 years
Number of Participants with a Clinically Significant Change from Baseline in Electrocardiograms (ECGs)	Baseline (Screening; up to 28 days pre-dose) up to Month 13
Number of Participants with a Clinically Significant Change from Baseline in Clinical Laboratory Tests	Baseline (Screening; up to 28 days pre-dose) up to Month 13
Maximum Plasma Concentration (Cmax) of Sotorasib	Day 1 up to Month 3
Time to Reach Maximum Plasma Concentration (tmax) of Sotorasib	Day 1 up to Month 3
Area Under the Plasma Concentration-time Curve (AUC) of Sotorasib	Day 1 up to Month 3
Progression-free Survival (PFS)	Up to 6 years
Overall Survival (OS)	Up to 6 years

Trial Locations

Locations (67)

Texas Oncology-Dallas Presbyterian Hospital; 🇺🇸 Dallas, Texas, United States

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

Northport Veterans Affairs Medical Center; 🇺🇸 Northport, New York, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

Texas Oncology - Flower Mound; 🇺🇸 Dallas, Texas, United States

Texas Oncology - Medical City Dallas; 🇺🇸 Dallas, Texas, United States

Universitair Ziekenhuis Antwerpen; 🇧🇪 Edegem, Belgium

Sahlgrenska Universitetssjukhuset; 🇸🇪 Goteborg, Sweden

Azienda Socio Sanitaria Territoriale di Monza Ospedale San Gerardo; 🇮🇹 Monza (MB), Italy

Hopital Cochin; 🇫🇷 Paris, France

Centre Hospitalier de Nantes - Hôpital Nord Laënnec; 🇫🇷 Saint Herblain, France

Universite Catholique de Louvain Cliniques Universitaires Saint Luc; 🇧🇪 Bruxelles, Belgium

Baptist MD Anderson Cancer Center; 🇺🇸 Jacksonville, Florida, United States

Asklepios - Fachkliniken München-Gauting; 🇩🇪 Gauting, Germany

Jessa Ziekenhuis - Campus Virga Jesse; 🇧🇪 Hasselt, Belgium

Allegheny Health Network Cancer Institute at Allegheny General Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

Texas Oncology-Denton; 🇺🇸 Denton, Texas, United States

Hospital Universitari i Politecnic La Fe; 🇪🇸 Valencia, Comunidad Valenciana, Spain

Norrlands Universitetssjukhus; 🇸🇪 Umea, Sweden

Istituti Fisioterapici Ospitalieri Regina Elena San Gallicano; 🇮🇹 Rome, Italy

Baptist Health Lexington; 🇺🇸 Lexington, Kentucky, United States

Gundersen Health System; 🇺🇸 La Crosse, Wisconsin, United States

Hospital Universitario Puerta de Hierro Majadahonda; 🇪🇸 Majadahonda, Madrid, Spain

Texas Oncology - Baylor; 🇺🇸 Dallas, Texas, United States

Hospital del Mar; 🇪🇸 Barcelona, Cataluña, Spain

Gavle Sjukhus; 🇸🇪 Gavle, Sweden

Azienda Ospedaliera di Rilievo Nazionale Specialistica dei Colli Monaldi; 🇮🇹 Napoli, Italy

Gazi Universitesi Saglik Arastirma ve Uygulama Merkezi Gazi Hastanesi; 🇹🇷 Ankara, Turkey

Hôpital Sainte Musse; 🇫🇷 Toulon Cedex, France

Centre Hospitalier Universitaire de Limoges - Hopital Dupuytren; 🇫🇷 Limoges Cedex, France

Centre Hospitalier Universitaire Régional de Lille - Hôpital Albert Calmette; 🇫🇷 Lille Cedex, France

Texas Oncology - Northeast Texas; 🇺🇸 Paris, Texas, United States

Azienda Ospedaliera Universitaria San Luigi Gonzaga; 🇮🇹 Orbassano (TO), Italy

Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi; 🇹🇷 Edirne, Turkey

Centre Hospitalier Universitaire de Montpellier - Val d Aurelle; 🇫🇷 Montpellier Cedex 5, France

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Cataluña, Spain

Universitetssjukhuset i Linkoping; 🇸🇪 Linkoping, Sweden

Centre Hospitalier Universitaire de Liege - Sart Tilman; 🇧🇪 Liege, Belgium

Skanes Universitetssjukhus; 🇸🇪 Lund, Sweden

Centre Hospitalier Universitaire de Toulouse - Hopital Larrey; 🇫🇷 Toulouse Cedex 9, France

Centre Hospitalier Universitaire de Bordeaux - Hopital Haut Leveque; 🇫🇷 Pessac Cedex, France

Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou; 🇫🇷 Rennes, France

Texas Oncology- Mckinney; 🇺🇸 McKinney, Texas, United States

Indiana University Melvin and Bren Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

Duke University Medical Center, Morris Cancer Clinic; 🇺🇸 Durham, North Carolina, United States

Oncology Consultants PA; 🇺🇸 Houston, Texas, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Arizona Oncology Associates Professional Corporation; 🇺🇸 Tucson, Arizona, United States

Alabama Oncology; 🇺🇸 Birmingham, Alabama, United States

City of Hope at Long Beach Elm; 🇺🇸 Duarte, California, United States

Northwest Georgia Oncology Centers PC; 🇺🇸 Marietta, Georgia, United States

Frederick Memorial Hospital; 🇺🇸 Frederick, Maryland, United States

Englewood Hospital and Medical Center; 🇺🇸 Englewood, New Jersey, United States

James J Peters VA Medical Center; 🇺🇸 Bronx, New York, United States

Laura and Isaac Perlmutter Cancer Center at New York University Langone; 🇺🇸 New York, New York, United States

State University of New York Upstate Medical University; 🇺🇸 Syracuse, New York, United States

University of Pittsburgh Medical Center Cancer Pavillion; 🇺🇸 Pittsburgh, Pennsylvania, United States

Texas Oncology - Plano East; 🇺🇸 Dallas, Texas, United States

Odense Universitetshospital; 🇩🇰 Odense C, Denmark

Institut Sainte Catherine; 🇫🇷 Avignon cedex 9, France

Klinikum und Fachbereich Medizin Johann Wolfgang Goethe-Universität Frankfurt am Main; 🇩🇪 Frankfurt am Main, Germany

Universitätsklinikum Köln; 🇩🇪 Koeln, Germany

Nederlands Kanker Instituut Antoni van Leeuwenhoekziekenhuis; 🇳🇱 Amsterdam, Netherlands

Hospital Clinico Universitario de Santiago; 🇪🇸 Santiago de Compostela, Galicia, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Koc Universitesi Hastanesi; 🇹🇷 Istanbul, Turkey

Medical University of South Carolina, Hollings Cancer Center; 🇺🇸 Charleston, South Carolina, United States