Adagrasib in Patients With KRASG12C-mutant NSCLC Who Are Elderly or Have Poor Performance Status

NSCLC Stage IV Clinical Trial

— ADEPPT  

Official title:

A Multicentre, Single-arm Phase II Trial of Adagrasib in Patients With KRASG12C-mutant NSCLC, Including the Elderly (≥70 Years) or Patients With Poor Performance Status

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05673187
• Other study ID #: ETOP 22-22
• Secondary ID: 2022-002736-31
• Status: Recruiting
• Phase: Phase 2
• Start date: June 12, 2023
• Est. completion date: March 1, 2026

Study information

• Verified date: April 2024
• Source: ETOP IBCSG Partners Foundation
• Contact: Heidi Roschitzki, PhD
• Phone: +41 31 511 94 00
• Email: heidi.roschitzki[@]etop.ibcsg.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

ADEPPT is an international, multicentre, single-arm phase II trial. The protocol treatment consists of adagrasib, which is administered at a dose of 600 mg orally, twice daily until progression or unacceptable toxicity.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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: March 1, 2026
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically or cytologically confirmed stage IV NSCLC.

2. KRASG12C-mutation by local testing (by tissue or ctDNA).

3. 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).

4. Life expectancy =12 weeks.

5. Measurable disease according to RECIST v1.1.

6. Age =18 years with ECOG PS 2 (cohort 1), or age =70 years with ECOG PS 0-1 (cohort 2).

7. Adequate haematological, renal and liver function

8. Men and women of childbearing potential must agree to use use highly effective contraceptive methods.

9. Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum beta HCG pregnancy test within 5 weeks before enrolment. Pregnancy test must be repeated within 7 days before the first dose of adagrasib treatment.Ability to comply with the trial protocol, in the investigator's judgment.

10. Written IC for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention, including the submission of mandatory biomaterial.

Exclusion Criteria:

1. Prior investigational therapy within 28 days or at least 5 half-lives before enrolment.

2. Prior treatment with an agent targeting KRASG12C.

3. 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 time period of minimum of 2 weeks must have elapsed from the last day of radiotherapy.

4. History of intestinal disease or major gastric surgery likely to alter absorption of study treatment or inability to swallow oral medications.

5. 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.

6. History of stroke or transient ischemic attack within 6 months prior to enrolment.

7. 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.

8. Known human immunodeficiency virus (HIV) infection.

9. Acute or chronic hepatitis B or C infection.

10. Women who are pregnant or in the period of lactation.

11. Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.

12. 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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• NSCLC Stage IV

Intervention

Drug:
• Adagrasib
Adagrasib is administered at a dose of 600 mg orally, twice daily until progression or unacceptable toxicity.

Locations

Country	Name	City	State
Belgium	Instiute Jules Bordet	Brussels
France	Centre Hospitalier d'Avignon	Avignon
France	Caen - CHU	Caen
France	Le Mans - CHG	Le Mans
France	Hôpital de Marseille	Marseille
Ireland	Beaumont Hospital	Dublin
Ireland	St James's Hospital	Dublin
Ireland	University Hospital Limerick	Limerick
Ireland	University Hospital Waterford	Waterford
Italy	Fondazione IRCCS Policlinico S. Matteo	Pavia
Italy	Santa Maria della Misericordia Hospital	Perugia
Italy	Istituto Nazionale Tumori "Regina Elena"	Rome
Italy	AULSS2 Marca Trevigiana Treviso	Treviso
Spain	Complejo Hospitalario Universitario a Coruña	A Coruña
Spain	Alicante University Hospital	Alicante
Spain	ICO Badalona - Hospital Germans Trias i Pujol	Badalona
Spain	Hospital de Basurto	Bilbao
Spain	ICO Bellvitge -H. Duran i Reynals / H. Bellvitge	L'Hospitalet De Llobregat
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario Puerta de Hierro	Madrid
Spain	Hospital General Universitario de Valencia (University Hospital Valencia)	Valencia
United Kingdom	Christie NHS Manchester	Manchester

Sponsors (2)

Lead Sponsor	Collaborator
ETOP IBCSG Partners Foundation	Mirati Therapeutics Inc.

Countries where clinical trial is conducted

Belgium,  France,  Ireland,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) per RECIST v1.1, assessed at 12 weeks.	The primary objective of this trial is to assess the clinical efficacy of adagrasib treatment, in terms of objective response as defined as the rate of patients achieving a best overall response [complete response (CR) or partial response (PR)] according to RECIST v1.1	From date of enrolment until 12 weeks post-enrolment
Secondary	Durable clinical benefit	Durable clinical benefit (DCB) is defined as the rate among all enrolled patients who are alive and without disease progression who achieve CR or PR, according to RECIST v1.1, or stable disease (SD) lasting for at least 24 weeks.	From date of enrolment until at least the 24-week assessment.
Secondary	Time-to-progression (TTP)	Time-to-progression (TTP) is defined as the time from the date of enrolment until the date of documented progression (according to RECIST v1.1). Censoring for patients without documented progression will occur at the date of last tumour assessment without PD. Patients without a post-baseline tumour assessment will be censored at the date of enrolment plus 1 day.	From the date of enrolment until last tumour assessment (approximately 20-26 months after enrolment of the first patient)
Secondary	Progression-free survival (PFS)	Progression-free survival (PFS) is defined as the time from the date of enrolment until the date of documented progression (according to RECIST v1.1) or death, if progression is not documented. Censoring (for patients without progression or death) will occur at the date of last tumour assessment. Patients without a post-baseline tumour assessment will be censored at the date of enrolment plus 1 day.	From the date of enrolment until last tumour assessment (approximately 20-26 months after enrolment of the first patient)
Secondary	Overall survival (OS)	Overall survival (OS) is defined as the time from the date of enrolment until the date of death from any cause. Censoring for patients who are not reported as dead will occur at the last date they are known to be alive. Data for patients who do not have post-baseline information will be censored at the date of enrolment plus 1 day.	From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
Secondary	Safety and tolerability	The toxicity and safety profile of the protocol treatment will be evaluated by: Adverse events (AEs) according to CTCAE v5.0 (any-cause, as well as treatment-related) including AEs leading to dose delays and/or interruptions, withdrawal of protocol treatment, and death; Severe and serious AEs; Deaths	From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
Secondary	Laboratory parameters and abnormalities 1	Hemoglobin [g/dl]	From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
Secondary	Laboratory parameters and abnormalities 2	Platelet count [G/L]	From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
Secondary	Laboratory parameters and abnormalities 3	White blood cell count [G/L]	From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
Secondary	Vital signs 1	Blood pressure systolic [mmHg]	From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
Secondary	Vital signs 2	Blood pressure diastolic [mmHG]	From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
Secondary	Vital signs 3	Heart rate [beats/min]	From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
Secondary	Vital signs 4	Body temperature [°C]	From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
Secondary	Patient-reported outcomes NFLSI-17	Patient-reported symptoms and functioning will be assessed by NCCN-Functional Assessment of Cancer Therapy (FACT) Lung Symptom Index-17 (NFLSI-17).	From the date of screening until patient's end of treatment (approximately 20-26 months after enrolment of the first patient)
Secondary	Patient-reported outcomes PRO-CTCAE®	The most commonly reported treatment-related adverse effects of adagrasib (diarrhoea and vomiting) that are not covered by the NFLSI-17 will be assessed by the NCI Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®).	From the date of screening until patient's end of treatment (approximately 20-26 months after enrolment of the first patient)