A study of adagrasib for patients with KRASG12C-mutant non-small cell lung cancer (NSCLC), who are elderly or who are unwell because of their lung cancer.
- Conditions
- Patients with KRASG12C-mutant stage IV NSCLC that had prior chemotherapy and/or immune-checkpoint inhibition or both.MedDRA version: 21.1Level: PTClassification code 10029515Term: Non-small cell lung cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2022-002736-31-IE
- Lead Sponsor
- ETOP IBCSG Partners Foundation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 68
- Histologically or cytologically confirmed stage IV NSCLC
- KRASG12C-mutation by local testing (by tissue or ctDNA)
- Prior treatment with at least one line of systemic therapy for NSCLC (e.g., platinum-based doublet chemotherapy and/or immune-checkpoint inhibition or both).
- Life expectancy =12 weeks
- Measurable disease according to RECIST v1.1
- Age =18 years with ECOG PS 2 (cohort 1), or age =70 years with ECOG PS 0-1 (cohort 2)
- Adequate haematological, renal and liver function
- Negative pregnancy test for patients of childbearing potential
- Ability to comply with the trial protocol, in the investigator's judgment.
-Written informed consent for protocol treatment must be signed and dated by the patient and the investigator prior to any trial-related intervention, including the submission of mandatory biomaterial.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 34
-Prior investigational therapy within 28 days or at least 5 half-lives before enrolment
-Prior treatment with an agent targeting KRASG12C
-Leptomeningeal disease or untreated brain metastases:
– Patient should be neurologically stable for at least 2 weeks before enrolment, without the need for corticosteroids, except for prednisone (or its equivalent) at a dose of =10 mg daily
– For patients with definitively treated brain metastases, a minimum of 2 weeks must have elapsed from the last day of radiotherapy
- History of intestinal disease or major gastric surgery likely to alter absorption of study treatment or inability to swallow oral medications.
Any of the following cardiac abnormalities:
– Unstable angina pectoris or myocardial infarction within 6 months prior to enrolment.
– Symptomatic or uncontrolled atrial fibrillation within 6 months prior to enrolment.
– Congestive heart failure =NYHA Class 3 within 6 months prior to enrolment.
– Prolonged QTc interval >480 ms or family or medical history of congenital Long QT Syndrome
-History of stroke or transient ischemic attack within 6 months prior to enrolment
-Ongoing need for treatment with concomitant medication with any of the following characteristics: known risk of Torsades de Pointes; substrate of CYP3A with narrow therapeutic index; strong inducer of CYP3A and/or P-gp; strong inhibitor of BCRP; and proton pump inhibitors that cannot be switched to alternative treatment prior to enrolment
-Known human immunodeficiency virus (HIV) infection
-Acute or chronic hepatitis B or C infection. Note that the following are permitted:
a. Patients treated for hepatitis C (HCV) with no detectable viral load at screening;
b. Patients treated for HIV with no detectable viral load for at least 1 month prior to enrolment; and
c. Patients with hepatitis B (HBV) receiving prophylaxis against reactivation of hepatitis B (either [HBsAg-positive with normal ALT and HBV DNA <2,000 IU/mL or <10,000 copies/mL] or [HBsAg-negative and anti-HBcAg-positive])
-Women who are pregnant or in the period of lactation
-Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study
-Judgement by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Secondary Objective: The secondary objectives refer to the evaluation of measures of clinical efficacy including durable clinical benefit (DCB), time-to-progression (TTP), progression-free survival (PFS), overall survival (OS), overall safety and patient-related outcomes.;Primary end point(s): Objective Response Rate (ORR) per RECIST v1.1, assessed at 12 weeks.;Timepoint(s) of evaluation of this end point: final analysis;Main Objective: The primary objective of this trial is to assess the clinical efficacy of adagrasib treatment, in terms of objective response, in patients with KRASG12C-mutant NSCLC, including the elderly (=70 years) or patients with poor performance status (ECOG PS=2).
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Durable clinical benefit (DCB)<br>- Time to progression (TTP)<br>- Progression-free Survival (PFS)<br>- Overall Survival (OS)<br>- Safety<br>- Patient-related outcomes;Timepoint(s) of evaluation of this end point: - DCB: final analysis<br>- TTP: final analysis<br>- PFS: final analysis<br>- OS: final analysis<br>- Safety: every 3 month and at final analysis<br>-Patient-related outcomes: final analysis<br>