A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer

JRCT ID: jRCT2041230093

Registered date:18/10/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Carcinoma, Non-Small-Cell Lung
• Date of first enrollment: 20/12/2023
• Target sample size: 161
• Countries of recruitment: China,Japan,Spain,Japan,United Kingdom Of Great Britain,Japan,Republic Of Korea,Japan,Turkey,Japan,United States Of America,Japan
• Study type: Interventional

Intervention(s)

Capmatinib
Capmatinib will be administered orally.
Phase 1 (Combination Dose Selection):capmatinib 400 milligrams (mg) orally twice daily
Phase 2 (Dose Expansion): will receive capmatinib in combination with amivantamab at the RP2CD (recommended Phase 2 combination dose) determined by the SET (study evaluation team) in Phase 1.

Amivantamab
Amivantamab will be administered as IV infusion
Phase 1 (Combination Dose Selection):amivantamab 700 mg intravenous (IV) infusion (for body weight less than 80 kilograms [kg]) or 1050 mg IV infusion (for body weight greater than or equal to 80 kg)
Phase 2 (Dose Expansion): will receive capmatinib in combination with amivantamab at the RP2CD determined by the SET in Phase 1.

Outcome(s)

Primary Outcome

- Phase 1: Number of Participants with Adverse events (AEs) by Severity
Up to 2 years 1 month
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the intervention. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.

- Phase 1: Number of Participants with Dose Limiting Toxicities (DLTs)
Cycle 1 (Day 1 through Day 28)
The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, hematologic toxicity, pulmonary toxicity, liver enzyme elevation, or treatment delay greater than (>) 28 days due to unresolved toxicity.

- Phase 2: Objective Response Rate
Up to 2 years 1 month
ORR is defined as the percentage of participants who achieve either a confirmed partial response (PR) or complete response (CR), using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Secondary Outcome

- Phase 1: Number of Participants with AEs by Severity
Up to 2 years 1 month
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the intervention. Severity will be graded according to the NCI-CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.

-Phase 1: Number of Participants with Abnormalities in Clinical Laboratory Parameters
Up to 2 years 1 month
Number of participants with abnormalities in clinical laboratory parameters (serum chemistry, hematology, coagulation, serology, and urinalysis) will be reported.

-Phase 2 : Duration of Response (DoR)
Up to 2 years 1 month
DoR is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death from any case, whichever comes first, for participants who have PR or CR.

-Phase 2: Disease Control Rate (DCR)
Up to 2 years 1 month
DCR is defined as the percentage of participants who achieve a PR, CR, or stable disease using RECIST version 1.1.

-Phase 2: Progression Free Survival (PFS)
Up to 2 years 1 month
PFS is defined as the time from first dose date until the date of disease progression or death, whichever comes first, based on investigator assessment using RECIST version 1.1

-Phase 2: Overall Survival (OS)
Up to 2 years 1 month
OS is defined as the time from the date of administration of the first study treatment until the date of death due to any cause.

-Phase 2: Time to Subsequent Therapy (TTST)
Up to 2 years 1 month
TTST is defined as the time from the date of administration of the first study treatment to the start date of the subsequent anticancer therapy following study treatment discontinuation, or death, whichever comes first.

-Phase 2 (Cohort 1A): Change from Baseline in Health-related Quality of Life in (HRQoL) as Assessed by European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score
Baseline up to 2 years 1 month
EORTC-QLQ-C30 is a self-administered, 30-item questionnaire developed to assess the HRQoL of cancer participants.

-Phase 2 (Cohort 1A): HRQoL as Assessed by Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ) Scale Score
Up to 2 years 1 month
NSCLC-SAQ assesses patient-reported symptom severity associated with NSCLC.

-Phase 2 (Cohort 1A): HRQoL as Assessed by EuroQol 5-Dimension 5- Level (EQ-5D-5L) Scale Score
Up to 2 years 1 month
EQ-5D-5L is a self-administered, standardized measure of health status.

-Phase 2 (Cohort 1A): HRQoL as Assessed by Patient-reported Outcomes Measurement Information System Short Form Version 2.0 - Physical Function 8c (PROMIS PF 8c) Scale Score
Up to 2 years 1 month
PROMIS PF 8c is an 8-item fixed length short form derived from the PROMIS Physical Function item bank. It assesses activities of daily living, mobility, and global impact of physical functioning.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

'- Previously diagnosed with histologically or cytologically confirmed unresectable Stage IV (metastatic) non-small cell lung cancer (NSCLC) (any histology)
- May have: definitively, locally treated brain metastases that are clinically stable and asymptomatic for greater than (>) 2 weeks and who are off or receiving low-dose corticosteroid treatment (less than or equal to [<=]10 milligrams (mg) prednisone or equivalent) for at least 2 weeks prior to start of study treatment
- May have a prior malignancy (other than the disease under study) the natural history or treatment of which is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- A participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study

Exclude criteria

- Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
- Participant has impairment of the gastrointestinal function that could affect absorption of capmatinib or is unable or unwilling to swallow tablets
- Participant has symptomatic central nervous system (CNS) metastases which are neurologically unstable or have required increasing doses of steroids >10 mg prednisone or equivalent within the 2 weeks prior to study entry to manage CNS symptoms
- Participant has uncontrolled tumor-related pain: Symptomatic lesions amenable to palliative radiotherapy (example, bone metastases, or metastases causing nerve impingement) should be treated more than 7 days prior to the administration of the first study treatment

Related Information

• Primary Sponsor: Nakama Takahiro
• Secondary ID(s): NCT05488314,2022-000485-18