Clinical trial NCT05673187: Adagrasib in Patients With KRASG12C-mutant NSCLC Who Are Elderly or Have Poor Performance Status
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: NSCLC Stage IV
KRAS P.G12C
Lead sponsor: ETOP IBCSG Partners Foundation
Sponsor class: NETWORK
Collaborators: name: Mirati Therapeutics Inc.
First posted: 2023-01-06
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR) per RECIST v1.1, assessed at 12 weeks.
timeFrame: From date of enrolment until 12 weeks post-enrolment
Secondary outcomes:
measure: Durable clinical benefit
timeFrame: From date of enrolment until at least the 24-week assessment.
measure: Time-to-progression (TTP)
timeFrame: From the date of enrolment until last tumour assessment (approximately 20-26 months after enrolment of the first patient)
measure: Progression-free survival (PFS)
timeFrame: From the date of enrolment until last tumour assessment (approximately 20-26 months after enrolment of the first patient)
measure: Overall survival (OS)
timeFrame: From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
measure: Safety and tolerability
timeFrame: From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
measure: Laboratory parameters and abnormalities 1
timeFrame: From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
measure: Laboratory parameters and abnormalities 2
timeFrame: From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
measure: Laboratory parameters and abnormalities 3
timeFrame: From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
measure: Vital signs 1
timeFrame: From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
measure: Vital signs 2
timeFrame: From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
measure: Vital signs 3
timeFrame: From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
measure: Vital signs 4
timeFrame: From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)
measure: Patient-reported outcomes NFLSI-17
timeFrame: From the date of screening until patient's end of treatment (approximately 20-26 months after enrolment of the first patient)
measure: Patient-reported outcomes PRO-CTCAE®
timeFrame: From the date of screening until patient's end of treatment (approximately 20-26 months after enrolment of the first patient)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Instiute Jules Bordet
city: Avignon
country: France
facility: Centre Hospitalier d'Avignon
city: Caen
country: France
facility: Caen - CHU
city: Le Mans
country: France
facility: Le Mans - CHG
city: Marseille
country: France
facility: Hôpital de Marseille
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: St James's Hospital
city: Limerick
country: Ireland
facility: University Hospital Limerick
city: Waterford
country: Ireland
facility: University Hospital Waterford
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico S. Matteo
city: Perugia
country: Italy
facility: Santa Maria della Misericordia Hospital
city: Rome
country: Italy
facility: Istituto Nazionale Tumori "Regina Elena"
city: Treviso
country: Italy
facility: AULSS2 Marca Trevigiana Treviso
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario a Coruña
city: Alicante
country: Spain
facility: Alicante University Hospital
city: Badalona
country: Spain
facility: ICO Badalona - Hospital Germans Trias i Pujol
city: Bilbao
country: Spain
facility: Hospital de Basurto
city: L'Hospitalet De Llobregat
country: Spain
facility: ICO Bellvitge -H. Duran i Reynals / H. Bellvitge
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia (University Hospital Valencia)
city: Manchester
country: United Kingdom
facility: Christie NHS Manchester
Study officials:
affiliation: Beaumont RCSI Cancer Centre, Beaumont Hospital
name: Jarushka Naidoo
role: STUDY_CHAIR
References: