Phase II Multicenter Trial of Adagrasib in KRASG12C-Mutant NSCLC Patients Aged ≥70 or with ECOG PS=2

Trial ID: 2023-510463-35-00
Protocol: ETOP 22-22 ADEPPT
Sponsor: ETOP IBCSG Partners Foundation

Trial statistics

science

test molecule

location_city

research sites

public

countries

medical_information

diseases

person_search

investigators

handshake

vendors

Diseases & Conditions

K-ras gene mutation Non-small cell lung cancer

Objectives

The primary objective of this trial is to assess the **clinical efficacy** of adagrasib treatment in patients with **KRASG12C-mutant non-small cell lung cancer (NSCLC)**. This evaluation focuses on the objective response in patients, including those who are elderly (≥70 years) or have a poor performance status (ECOG PS=2). The clinical relevance of this objective lies in determining the potential of adagrasib to provide a therapeutic benefit in a specific subset of NSCLC patients, which could inform treatment strategies and improve patient outcomes.

The secondary objectives involve evaluating measures of clinical efficacy, including:

Durable clinical benefit (DCB)
Time-to-progression (TTP)
Progression-free survival (PFS)
Overall survival (OS)
Overall safety
Patient-related outcomes

These secondary objectives aim to provide a comprehensive understanding of the treatment's impact on disease progression, survival, safety, and quality of life, which are critical factors in the management of NSCLC.

Participants

The clinical trial involves a total of **15 participants** diagnosed with **KRASG12C-mutant non-small cell lung cancer (NSCLC)**. The study population includes both male and female subjects, with an age range starting from 18 years. Participants are divided into two cohorts: Cohort 1 consists of individuals aged 18 years and older with a poor performance status (ECOG PS=2), while Cohort 2 includes elderly participants aged 70 years and above with a performance status of ECOG PS=0-1. The trial population was selected based on specific criteria, including a confirmed stage IV NSCLC with a KRASG12C mutation, prior treatment with at least one line of systemic therapy, and a life expectancy of at least 12 weeks. Participants are required to have adequate hematological, renal, and liver function, and must be able to comply with the trial protocol. The study includes a vulnerable population, and all participants provided written informed consent prior to any trial-related intervention. Lifestyle considerations such as diet and physical activity are not specified in the available data.

Plans and Procedures

The clinical trial is designed to evaluate the **clinical efficacy** of **adagrasib** in patients with **KRASG12C-mutant non-small cell lung cancer (NSCLC)**, including those who are elderly or have a poor performance status. This is a multicenter, single-arm, phase II trial. The primary objective is to assess the objective response rate (ORR) per RECIST v1.1, evaluated at 12 weeks. Secondary endpoints include durable clinical benefit, time to progression, progression-free survival, overall survival, safety, and patient-related outcomes. The trial is expected to conclude by June 30, 2026, with recruitment having commenced on June 12, 2023.

Participants will be involved in the study for a maximum treatment period of 13 months, during which they will receive **adagrasib** in the form of film-coated tablets administered orally. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor treatment response and safety, and an end-of-study visit to assess final outcomes. Inclusion criteria require participants to have histologically or cytologically confirmed stage IV NSCLC with a **KRASG12C mutation**, prior treatment with at least one line of systemic therapy, a life expectancy of at least 12 weeks, and measurable disease according to RECIST v1.1. Participants must be at least 18 years old with an ECOG performance status of 2, or at least 70 years old with an ECOG performance status of 0-1. Adequate hematological, renal, and liver function are also required, along with a negative pregnancy test for those of childbearing potential.

Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they are unable to comply with the trial protocol. Written informed consent is mandatory before any trial-related intervention, including the submission of mandatory biomaterial. The trial is not classified as low intervention and is conducted under the sponsorship of Mirati Therapeutics Inc. The investigational product, **adagrasib**, is a **KRAS inhibitor** that irreversibly and selectively binds to **KRASG12C**. The trial does not involve any pediatric formulations or orphan drug designations.

Treatment

The clinical trial involves the administration of **Adagrasib**, a **KRAS inhibitor** that irreversibly and selectively binds to **KRASG12C**. The experimental medication is provided in the form of a **film-coated tablet**. The active substance, **adagrasib**, is chemically synthesized and is identified by the sponsor product code **MRTX849**. The maximum daily dose of adagrasib is 1200 mg, with a total maximum dose of 468,000 mg over a treatment period of up to 13 weeks. The route of administration is oral, and the medication is not formulated for pediatric use. The trial aims to evaluate the clinical efficacy of adagrasib in patients with **KRASG12C-mutant non-small cell lung cancer (NSCLC)**, including those who are elderly (≥70 years) or have a poor performance status (ECOG PS=2).

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of adagrasib to assess its therapeutic potential. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial is conducted under the sponsorship of Mirati Therapeutics Inc., and the pharmaceutical form of the medication is consistent with standard clinical practices for oral administration.

Efficacy

The clinical trial aims to assess the efficacy of **adagrasib** in patients with KRASG12C-mutant non-small cell lung cancer (NSCLC), including those who are elderly (≥70 years) or have a poor performance status (ECOG PS=2). The primary endpoint for evaluating efficacy is the Objective Response Rate (ORR) as per RECIST v1.1, which will be assessed at 12 weeks. Secondary endpoints include Durable Clinical Benefit (DCB), Time to Progression (TTP), Progression-Free Survival (PFS), Overall Survival (OS), safety, and patient-related outcomes.

Measurements of efficacy parameters will be conducted using validated scales and criteria, such as RECIST v1.1, to ensure consistency and reliability in the assessment of tumor response. The trial will involve regular monitoring and data collection at specified intervals, with the primary assessment occurring at the 12-week mark. The analysis of these parameters will be performed to determine the clinical benefit of **adagrasib** in the specified patient population.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Most important inclusion criterias:- 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.

cancel

Exclusion Criteria

-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

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Not Recruiting	12 Jun 2023	5
France	Not Recruiting	12 Jun 2023	10
Ireland	Not Recruiting	12 Jun 2023	8
Italy	Not Recruiting	12 Jun 2023	15
Spain	Not Recruiting	12 Jun 2023	15