A Safety and Efficacy Study of INC280 and Gefitinib in Patients With EGFR Mutated, c-MET-amplified NSCLC Who Have Progressed After EGFRi Treatment

NCT01610336 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CINC280X22022011-002569-39
• Study Type: interventional
• Target: 161
• Locations: 14 countries
• Sites: 31

Brief Summary

This study assessed the safety and efficacy of escalating doses INC280 when added to gefitinib in patients with lung cancer that were known to have dysregulation of the c-MET pathway and who had failed after benefiting on a prior treatment with either gefitinib or erlotinib.

Conditions

Non-small Cell Lung Cancer

Keywords

EGFR; c-MET; Lung cancer; Gefitinib; Erlotinib; Non-small cell lung cancer (NSCLC); lung adenocarcinoma; large-cell lung carcinoma

Outcome Measures

Primary Outcomes (2)

• Phase Ib: Frequency of Dose Limiting Toxicities (DLTs)

  A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.

  Up to 215 weeks

• Phase II : Overall Response Rate (ORR)

  Overall response rate is defined as the proportion of patients with best overall response (BOR) of complete response (CR) or partial response (PR), as per RECIST 1.1 (Overall Response (OR) = CR + PR). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

  Until disease progression, up to 60.8 weeks

Secondary Outcomes (12)

• Phase Ib and II: Number of Participants With Adverse Events (AEs)

  Up to 421 weeks

• Phase Ib and II: Number of Participants With Serious Adverse Events (SAEs)

  Up to 421 weeks

• Phase Ib and II: Number of Patients With Dose Reductions of INC280 by Dose Level

  Up to 417 weeks

• Phase Ib and II: Number of Patients With Dose Interruptions of Gefitinib by Dose Level

  Up to 417 weeks

• Phase II: Overall Survival (OS)

  From date of treatment until death due to any cause, up to 70.2 months

Other Outcomes (1)

• Phase I: Percentage of Change From Baseline in C-MET H Score at Cycle 1 Day 15

  Baseline, Day 15 of cycle 1 (Cycle=28days)

Study Arms (11)

INC280 100 mg Cap QD Phase Ib

EXPERIMENTAL

cap=capsule; QD=once daily

Drug: INC280; Drug: Gefitinib

INC280 200 mg Cap QD Phase Ib

EXPERIMENTAL

cap=capsule; QD=once daily

Drug: INC280; Drug: Gefitinib

INC280 400 mg Cap QD Phase Ib

EXPERIMENTAL

cap=capsule; QD=once daily

Drug: INC280; Drug: Gefitinib

INC280 800 mg Cap QD Phase Ib

EXPERIMENTAL

cap=capsule; QD=once daily

Drug: INC280; Drug: Gefitinib

INC280 200 mg Cap BID Phase Ib

EXPERIMENTAL

cap=capsule; BID=twice daily

Drug: INC280; Drug: Gefitinib

INC280 400 mg Cap BID Phase Ib

EXPERIMENTAL

cap=capsule; BID=twice daily

Drug: INC280; Drug: Gefitinib

INC280 600 mg Cap BID Phase Ib

EXPERIMENTAL

cap=capsule; BID=twice daily

Drug: INC280; Drug: Gefitinib

INC280 200 mg Tab BID Phase Ib

EXPERIMENTAL

tab=tablet; BID=twice daily

Drug: INC280; Drug: Gefitinib

INC280 400 mg Tab BID Phase Ib

EXPERIMENTAL

tab=tablet; BID=twice daily

Drug: INC280; Drug: Gefitinib

INC280 400 mg Cap BID Phase II

EXPERIMENTAL

cap=capsule; BID=twice daily

Drug: INC280; Drug: Gefitinib

INC280 400 mg Tab BID Phase II

EXPERIMENTAL

tab=tablet; BID=twice daily

Drug: INC280; Drug: Gefitinib

Interventions

INC280 DRUG

During Phase Ib, INC280 was taken at escalating doses. During Phase II part, INC280 was taken at recommended Phase II dose.

Also known as: Capmatinib

INC280 100 mg Cap QD Phase Ib; INC280 200 mg Cap BID Phase Ib; INC280 200 mg Cap QD Phase Ib; INC280 200 mg Tab BID Phase Ib; INC280 400 mg Cap BID Phase II; INC280 400 mg Cap BID Phase Ib; INC280 400 mg Cap QD Phase Ib; INC280 400 mg Tab BID Phase II; INC280 400 mg Tab BID Phase Ib; INC280 600 mg Cap BID Phase Ib; INC280 800 mg Cap QD Phase Ib

Gefitinib DRUG

Gefitinib 250 mg taken once daily

INC280 100 mg Cap QD Phase Ib; INC280 200 mg Cap BID Phase Ib; INC280 200 mg Cap QD Phase Ib; INC280 200 mg Tab BID Phase Ib; INC280 400 mg Cap BID Phase II; INC280 400 mg Cap BID Phase Ib; INC280 400 mg Cap QD Phase Ib; INC280 400 mg Tab BID Phase II; INC280 400 mg Tab BID Phase Ib; INC280 600 mg Cap BID Phase Ib; INC280 800 mg Cap QD Phase Ib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented EGFR mutation
• Documented c-MET dysregulation
• Prior clinical benefit on EGFR inhibitors and then subsequent progression
• ≥ 18 year old
• Life expectancy of ≥ 3 months
• ECOG performance status ≤ 2

You may not qualify if:

• Unable to swallow tables once or twice daily
• Previous treatment with c-MET inhibitor
• Any unresolved toxicity from previous anticancer therapy greater than grade 1
• History of cystic fibrosis
• History of acute or chronic pancreatitis
• Unable to undergo MRI or CT scans
• Known history of HIV
• Undergone a bone marrow or solid organ transplant
• Clinically significant wound or lung tumor lesions with increased likelihood of bleeding
• Pregnant or nursing

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (31)

Novartis Investigative Site

Woolloongabba, Queensland, 4102, Australia

Location

Novartis Investigative Site

East Bentleigh, Victoria, 3165, Australia

Location

Novartis Investigative Site

Auckland, Australia

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Guangzhou, Guangdong, 51000, China

Location

Novartis Investigative Site

Shanghai, Shanghai Municipality, 200433, China

Location

Novartis Investigative Site

Beijing, 100039, China

Location

Novartis Investigative Site

Guangzhou, 510060, China

Location

Novartis Investigative Site

Strasbourg, 67091, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Frankfurt, 60590, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Ramat Gan, 52621, Israel

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Modena, MO, 41124, Italy

Location

Novartis Investigative Site

Koto Ku, Tokyo, 135 8550, Japan

Location

Novartis Investigative Site

Maastricht, AZ, 5800, Netherlands

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3015 GD, Netherlands

Location

Novartis Investigative Site

Singapore, 169610, Singapore

Location

Novartis Investigative Site

Gyeonggi-do, Korea, 10408, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 05505, South Korea

Location

Novartis Investigative Site

Seoul, Seocho Gu, 06591, South Korea

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 06351, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Tainan, 70403, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Bangkok, 10400, Thailand

Location

Related Publications (1)

• Wu YL, Zhang L, Kim DW, Liu X, Lee DH, Yang JC, Ahn MJ, Vansteenkiste JF, Su WC, Felip E, Chia V, Glaser S, Pultar P, Zhao S, Peng B, Akimov M, Tan DSW. Phase Ib/II Study of Capmatinib (INC280) Plus Gefitinib After Failure of Epidermal Growth Factor Receptor (EGFR) Inhibitor Therapy in Patients With EGFR-Mutated, MET Factor-Dysregulated Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 Nov 1;36(31):3101-3109. doi: 10.1200/JCO.2018.77.7326. Epub 2018 Aug 29.

  PMID: 30156984 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Adenocarcinoma of Lung

Interventions

capmatinib; Gefitinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2012
• First Posted: June 4, 2012
• Study Start: April 5, 2012
• Primary Completion: June 10, 2016
• Study Completion: May 27, 2020
• Last Updated: April 8, 2021
• Results First Posted: April 8, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share

Locations

TW (2); CN (4); TH (1); SG (1); JP (1); DE (2); FR (2); IL (1); NL (3); KR (5); AU (3); BE (1); IT (3); ES (2)