RECRUITING

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

Conditions

Non Small Lung Cancer Sotorasib advanced KRAS G12C-mutant 24-049

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.)

Official Title

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

Quick Facts

Study Start:2024-08-30

Study Completion:2026-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06582771

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 ≥ 10\^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 * 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 * 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.	* 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. * 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.

Inclusion Criteria

Exclusion 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 ≥ 10\^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
* 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
* 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.

* 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.
* 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.

Contacts and Locations

Study Contact

Gregory Riely, MD, PhD

CONTACT

646-608-3913

rielyg@mskcc.org

Kathryn Arbour, MD

CONTACT

646-608-3792

Principal Investigator

Gregory Riely, MD, PhD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer

Study Locations (Sites)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553

United States

Memorial Sloan Kettering Westchester

West Harrison, New York, 10604

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Gregory Riely, MD, PhD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-08-30

Study Completion Date2026-08

Study Record Updates

Study Start Date2024-08-30

Study Completion Date2026-08

Terms related to this study

Keywords Provided by Researchers

Sotorasib
advanced KRAS G12C-mutant
24-049

Additional Relevant MeSH Terms

Non Small Lung Cancer