A Study of Sotorasib in People With Non-Small Cell Lung Cancer

A Phase 2 Study of First-line Sotorasib for Patients With Advanced KRAS G12C-mutant Non-small Cell Lung Cancer

The researchers are doing this study to see if sotorasib is a safe and effective treatment for people with advanced non-small cell lung cancer (NSCLC) with a KRAS G12C mutation who have not received treatment for their cancer since it became advanced. (Participants have not received a "first-line therapy" since their cancer became advanced.)

Study Overview

• Status: Recruiting
• Conditions: Non Small Lung Cancer
• Intervention / Treatment: Drug: Sotorasib

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gregory Riely, MD, PhD; Phone Number: 646-608-3913; Email: rielyg@mskcc.org
• Study Contact Backup: Name: Kathryn Arbour, MD; Phone Number: 646-608-3792

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
      • Contact: Gregory Riely, MD, PhD; Phone Number: 646-608-3913
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
      • Contact: Gregory Riely, MD, PhD; Phone Number: 646-608-3913
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
      • Contact: Gregory Riely, MD, PhD; Phone Number: 646-608-3913
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk - Commack (Limited protocol activities)
      • Contact: Gregory Riely, MD, PhD; Phone Number: 646-608-3913
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester
      • Contact: Gregory Riely, MD, PhD; Phone Number: 646-608-3913
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Gregory Riely, MD, PhD; Phone Number: 646-608-3913
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau
      • Contact: Gregory Riely, MD, PhD; Phone Number: 646-608-3913

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent
• Biopsy-proven metastatic or recurrent non-small cell lung cancer
• KRAS G12C mutation on prior tumor biopsy or cell-free DNA (cfDNA) testing
• No prior therapy in the advanced setting
• Measurable disease per RECIST 1.1
• Karnofsky performance status (KPS) ≥ 70%
• Age ≥ 18

• Adequate organ function

  • Hemoglobin ≥ 9^9 g/dL
  • Platelets ≥ 75 x 10^9/L
  • Absolute neutrophil count (ANC) > 1.5 x 10^9/L
  • AST < 3 x ULN (if liver metastases are present, < 5 x ULN)
  • ALT < 3 x ULN (if liver metastases are present, < 5 x ULN)
  • Alkaline phosphatase < 2 x ULN (if liver or bone metastases are present,< 3 xULN)
  • Total bilirubin ≤1.5 x ULN; subjects with Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits
  • Serum creatinine < 1.5 x ULN or if available, calculated or measured creatinine clearance > 30 mL/min/1.73 m^2

In addition, patients must:

• Be willing to undergo pre-treatment and day 7-21 on-treatment tumor biopsies
• Decline first-line chemotherapy and/or anti-PD-(L)1 therapy, or previously have experienced disease progression after adjuvant or consolidation chemotherapy or anti-PD-(L)1 therapy for early stage (I-III) NSCLC

Before enrollment, a woman must be either:

• Not of childbearing potential: premenarchal; postmenopausal (>45 years of age with amenorrhea for at least 12 months); post-hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy

• Of childbearing potential and practicing effective method(s) of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies, as described below:

  • Practicing true abstinence (when this is in line with the preferred and usual lifestyle of the subject), which is defined as refraining from heterosexual intercourse during the entire period of the study, including up to 6 months after the last dose of study drug is given. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not consider an acceptable contraceptive method
• Have a sole partner who is vasectomized
• Practicing 2 methods of contraception, including one highly effective method (i.e., established use of oral, injected or implanted hormonal methods of contraception; placement of intrauterine device [IUD] or intrauterine system [IUS], AND, a second method (e.g., condom with spermicidal foam/gel/film/cream/suppository or collusive cap [diaphragm or cervical/vault caps] with spermicidal foam/gel/film/ cream/suppository) Subjects must agree to continue contraception throughout the study and continuing through at least 7 days after the last dose of study drug
• NOTE: If the childbearing potential changes after start of the study (e.g., woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) the woman must begin a highly effective method of birth control, as described above.
• A woman of childbearing potential must have a negative serum (b-human chorionic gonadotropin [b-hCG]) at Screening
• A man who is sexually active with a woman of childbearing potential must agree to use a condom with spermicidal foam/gel/film/cream/suppository and his partner must also be practicing a highly effective method of contraception (i.e., established use of oral, injected or implanted hormonal methods of required to use contraception. The subject must also not donate sperm during the study and for at least 7 days after receiving the last dose of study drug.

contraception; placement of an intrauterine device [IUD] or intrauterine system [IUS]). If the subject is vasectomized, he must still use a condom (with or without spermicide), but his female partner is not required to use contraception. The subject must also not donate sperm during the study and for at least 7 days after receiving the last dose of study drug.

Exclusion Criteria:

• Symptomatic brain metastases
• Any radiotherapy within 1 week of starting treatment on protocol
• Any major surgery within 1 week of starting treatment on protocol
• Exposure to prior adjuvant or consolidation anti-PD-1 or PD-(L)1 therapy for stage I-III disease within 12 weeks of start of initiation of sotorasib
• Unresolved > grade 1 toxicity from any previous treatment
• Prior history of > grade 1 pneumonitis from any previous treatment
• Congestive heart failure defined as New York Heart Association (NYHA) Class III-IV or hospitalization for congestive heart failure (any NYHA class) within 6 months of study Day 1 Gastrointestinal (GI) tract disease causing the inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, uncontrolled inflammatory GI disease (eg, Crohn's disease, ulcerative colitis)
• Positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg) o NOTE: Subjects with a prior history of HBV demonstrated by positive hepatitis B core antibody are eligible if they have at Screening 1) a negative HBsAg and 2) a HBV DNA (viral load) below the lower limit of quantification, per local testing. Subjects with a positive HBsAg due to recent vaccination are eligible if HBV DNA (viral load) is below the lower limit of quantification, per local testing.

Positive hepatitis C antibody (anti-HCV)

o NOTE: Subjects with a prior history of HCV, who have completed antiviral treatment and have subsequently documented HCV RNA below the lower limit of quantification per local testing are eligible.

• Other clinically active or chronic liver disease
• Currently enrolled in another investigational device or drug study, or less than 28 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)
• Use of known cytochrome P450 (CYP) 3A4 sensitive substrates (with a narrow therapeutic window), within 14 days or 5 half-lives (whichever is longer) of the drug or its major active metabolite, whichever is longer, prior to study day 1 that was not reviewed and approved by the principal investigator
• Use of strong inducers of CYP3A4 within 14 days or 5 half-lives (whichever is longer) prior to study day 1 that was not reviewed and approved by the principal investigator
• Use of P-gp substrates within 14 days or 5 half-lives (whichever is longer) prior to study day 1 that was not reviewed and approved by the principal investigator
• Patients who do not agree to pre-treatment and on-treatment tumor biopsies during the informed consent process will be excluded from the study. Patients who agree to pre-treatment and on-treatment tumor biopsies, but in whom either biopsy is ultimately deemed unsafe by the investigators/treatment team, will be allowed to participate in the study and will remain evaluable for the clinical endpoints.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sotorasib; All patients will start at sotorasib 960 mg (8 pills) daily within 7 days of completion of the pretreatment tumor biopsy.	Drug: Sotorasib; Sotorasib 960 mg (8 pills) daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to therapy	will be assessed with serial CT chest/abdomen/pelvis every 2 cycles (6 weeks), with response evaluated by RECIST 1.1	within 6 month of therapy

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Gregory Riely, MD, PhD, Memorial Sloan Kettering Cancer

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: August 30, 2024
• First Submitted That Met QC Criteria: August 30, 2024
• First Posted (Actual): September 3, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Sotorasib; advanced KRAS G12C-mutant; 24-049
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; sotorasib
• Other Study ID Numbers: 24-049

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No