A clinical trial to study the effect of Capmatinib in Indian patients with Metastatic NSCLC (MET exon 14 skipping mutation positive)

Phase 4

Recruiting

• Conditions: Malignant neoplasm of unspecifiedpart of bronchus or lung,

• Registration Number: CTRI/2022/05/042549
• Lead Sponsor: Novartis Healthcare Pvt Ltd

Brief Summary

This is a Phase IV, prospective, multicenter, open-label, interventional study to assess the safety and efficacy of capmatinib in Indian patients with MET exon 14 skipping mutation positive metastatic NSCLC in any line of therapy. The study will include molecular prescreening 28 days for patients who do not have documented MET exon 14 skipping mutation positive results screening period 28 days treatment period of 24 weeks 6  months, 400 mg BID treatment as continuation dosing end of treatment EOT visit and follow-up period of 30 days post last dose of study treatment. Completion of the followup period after the last dose of the study treatment will be considered as the End of Study EOS. Patients transitioning to PTA will also have to compete the EOS Visit assessment after the last dose administration of capmatinib which is as a part 6 months of treatment for the current study. The total study duration for 50 patients in the study will be approximately 2.5 years. The study will include approximately 50 Indian patients. During screening period patients will undergo screening procedures for meeting the eligibility for the study During the treatment phase, treatment will be administered as capmatinib 400 mg orally BID on a continuous dosing schedule for the duration of 24 weeks 6 months. Followup period of 30 days include safety evaluations after end of the study treatment. Completion of the follow-up period will be considered as the End of Study EOS.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-09-20
• Last Update Posted: 2025-07-03

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Signed informed consent must be obtained prior to participation in the study.
• Adult more than or equal to 18 years old at the time of informed consent.
• 3.Metastatic NSCLC (Stage IV, according to Version 8 of the AJCC Staging Manual) either treatment naïve or progressed (clinically and/or radiologically) on one or more lines of systemic therapy.
• Histologically or cytologically confirmed diagnosis of NSCLC with confirmed EGFR wild type and ALK rearrangement negative and who have tested positive MET exon14 skipping mutation Locally available MET report either by reverse transcriptase polymerase chain reaction RTPCR or NGS would be considered in case not available MET testing would be done through NGS based molecular prescreening done as part of the study.
• Patients must have recovered from all toxicities related to prior systemic therapies to grade less than or equal to 1 Common Terminology Criteria for Adverse Events CTCAE version 5.0. 6.
• At least one measurable lesion as defined by RECIST 1.1. 7.
• Patients must have adequate organ function including the following laboratory values at the screening visit.
• Absolute neutrophil count more than or equal to 1.5 x 109/L without growth factor support b.
• Platelets more than or equal to 100 x 109/L c.
• Hemoglobin more than or equal to 9 g/dL d.
• Calculated creatinine clearance using Cockcroft Gault formula more than or equal to 45 mL/min e.
• Total bilirubin less than or equal to 1.5 ULN upper limit of normal except in patients with Gilberts syndrome who may be included if total bilirubin is less than or equal to 3.0 x ULN and direct bilirubin is less than or equal to 1.5 x ULN f.
• AST less than or equal to 3 x ULN except for patients with liver metastasis, who may only be included if AST less than or equal to 5 x ULN g.
• ALT less than or equal to 3 x ULN except for patients with liver metastasis who may only be included if ALT less than or equal to 5 x ULN h.Alkaline phosphatase ALP less than or equal to 5.0 x ULN i.
• Patients with grade 1 or grade 2 serum amylase at the beginning of the study must be confirmed to have no signs and or symptoms suggesting pancreatitis or pancreatic injury e.g. elevated P amylase, abnormal imaging findings of pancreas etc.
• Eastern Cooperative Oncology Group ECOG performance status PS of 0 to 2.
• Willing and able to comply with scheduled visits treatment plan and laboratory tests.

Exclusion Criteria

• Prior treatment with any MET inhibitor or hepatocyte growth factor targeting therapy.
• Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years.
• Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers and completely resected carcinoma in situ of any type.
• Patients with symptomatic central nervous system CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
• Patients with known druggable molecular alterations such as ROS1 translocation or BRAF mutation etc which might be a candidate for alternative targeted therapies as applicable per local regulations and treatment guidelines.
• Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis i.e. affecting activities of daily living or requiring therapeutic intervention.
• Subject with clinically significant heart diseases like unstable angina acute myocardial infraction within 6 months prior to screening, NYHA class III IV congestive cardiac failure uncontrolled hypertension, arrhythmias or QTcF more than or equal to 470 ms on the screening ECG.
• Major surgery e.g. intra-thoracic intra-abdominal or intrapelvic within 4 weeks prior 2 weeks for resection of brain metastases to starting capmatinib or who have not recovered from side effects of such procedure.
• Video-assisted thoracic surgery and mediastinoscopy will not be counted as major surgery and patients can be enrolled in the program more than or equal to 1 week after the procedure.
• For all other anatomic sites including radiotherapy to thoracic vertebrae and ribs radiotherapy less than or equal to 2 weeks prior to starting capmatinib or patients who have not recovered from radiotherapyrelated toxicities.
• Palliative radiotherapy for bone lesions less than or equal to 2 weeks prior to starting capmatinib is allowed.
• Impairment of gastrointestinal GI function or GI disease that may significantly alter the absorption of capmatinib or patients who are unable to swallow oral tablets.
• Patients receiving treatment with strong inducers of CYP3A that cannot be discontinued at least 1 week prior to the start of treatment with capmatinib and for the duration of the study.
• Unable or unwilling to swallow tablets as per dosing schedule.
• Patients with known hypersensitivity to capmatinib and any of the excipients of capmatinib.
• Patients with any other severe, acute or chronic medical or psychotic conditions or significant abnormal physical findings that in the opinion of the investigator may increase the risk associated with study participation or that may interfere with the interpretation of study results.
• Patients with prior systemic anti-cancer chemotherapy immunotherapy biologic therapy vaccine and investigational agents within 4 weeks or less than or equal to 5 x half-life of the agent whichever is shorter before first dose of capmatinib.
• If previous treatment is a monoclonal antibody then the treatment must be discontinued at least 4 weeks before first dose of capmatinib.
• If previous treatment is an oral targeted agent, then the treatment must be discontinued at least 5 x half-life of the agent.
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 7 days after stopping study treatment.
• Highly effective contraception methods include: a.
• Total abstinence when this is in line with the preferred and usual lifestyle of the patient.
• Periodic abstinence e.g. calendar, ovulation, symptothermal, postovulation methods and withdrawal are not acceptable methods of contraception.
• Female sterilization have had surgical bilateral oophorectomy with or without hysterectomy total hysterectomy or bilateral tubal ligation at least six weeks before taking study treatment.
• In case of oophorectomy alone only when the reproductive status of the woman has been confirmed by followup hormone level assessment.
• Male sterilization at least 6 months prior to screening.
• For female patients on the study, the vasectomized male partner should be the sole partner for that patient.
• Use of oral estrogen and progesterone injected or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system, or other forms of hormonal contraception that have comparable efficacy failure rate less than or equal to 1% for example hormone vaginal ring or transdermal hormone contraception.
• In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking treatment.
• Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 7 days after stopping study treatment.
• A condom is required for all sexually active male patients to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner.
• In addition male patients must not donate sperm for the time period specified above.
• Any other condition that would in the Investigator judgment contraindicate patient’s participation in the clinical study due to safety concerns or compliance with clinical study procedures e.g. active infection including active hepatitis B and C SARS CoV2 inflammation intestinal obstruction unable to swallow medication Social or psychological issues etc.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Incidence of AEs, including SAEs after	Baseline Week 1, Week 4, Week 7, Week 10, Week 13, Week 16, Week 19, Week 22, Week 24 (EOT), EOS (30 days after EOT)
treatment initiation, changes in laboratory	Baseline Week 1, Week 4, Week 7, Week 10, Week 13, Week 16, Week 19, Week 22, Week 24 (EOT), EOS (30 days after EOT)
values, vital signs, and ECGs	Baseline Week 1, Week 4, Week 7, Week 10, Week 13, Week 16, Week 19, Week 22, Week 24 (EOT), EOS (30 days after EOT)
Tolerability dose interruptions, reductions,	Baseline Week 1, Week 4, Week 7, Week 10, Week 13, Week 16, Week 19, Week 22, Week 24 (EOT), EOS (30 days after EOT)
and dose intensity.	Baseline Week 1, Week 4, Week 7, Week 10, Week 13, Week 16, Week 19, Week 22, Week 24 (EOT), EOS (30 days after EOT)

Secondary Outcome Measures

Name	Time	Method
All assessed per RECIST 1.1 by	investigator assessment

Trial Locations

Locations (24)

Aadhar Hospital; 🇮🇳 Hisar, HARYANA, India

AIIMS; 🇮🇳 Khordha, ORISSA, India

All India Institute of Medical Sciences (AIIMS); 🇮🇳 Nagpur, MAHARASHTRA, India

Bhagwan Mahaveer Cancer Hospital & Research Centre; 🇮🇳 Jaipur, RAJASTHAN, India

Chittaranjan National Cancer Institute; 🇮🇳 Kolkata, WEST BENGAL, India

CIMET’s Inamdar Multispeciality Hospital; 🇮🇳 Pune, MAHARASHTRA, India

Father Muller Medical College Hospital; 🇮🇳 Kannada, KARNATAKA, India

Government Medical College; 🇮🇳 Kozhikode, KERALA, India

IPGMER and SSKM Hospital; 🇮🇳 Kolkata, WEST BENGAL, India

Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER); 🇮🇳 Pondicherry, PONDICHERRY, India

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Aadhar Hospital

🇮🇳Hisar, HARYANA, India

Dr Lovenish Goyal

Principal investigator

9896539142

drlovenish@gmail.com