Study of safety and efficacy of INC280 alone, and in combination with erlotinib, compared to chemotherapy, in advanced/metastatic non-small cell lung cancer patients with EGFR mutation and cMET amplificatio

Phase 1

• Conditions: on-small cell lung cancer; MedDRA version: 18.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-001241-84-GB
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-02-23
• Study Completion: 2018-12-05
• Last Update Posted: 20 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

Specific for Phase Ib:
? Must have received at least one line of systemic therapy, including one prior 1st generation (e.g., erlotinib, gefitinib) or 2nd generation (e.g., afatinib) EGFR TKI; any line of prior systemic chemotherapy is allowed
? cMET-amplification (GCN = 6) by FISH assessed from a biopsy or an archival tumor sample collected at or any time after the progression on prior 1st or 2nd generation EGFR TKI, determined locally or by a Novartis-designated central laboratory. Patients with known EGFRT-790M mutation are not eligible.
? Adequate organ function at screening including platelet count = 75 x 10^9/L
Specific for Phase II:
? Must have received one and only one prior line of 1st generation (e.g., erlotinib, gefitinib) or 2nd generation (e.g., afatinib) EGFR TKI for the treatment of locally advanced or metastatic NSCLC
? No prior chemotherapy is allowed, except patients, who switched from platinum-based chemotherapy to EGFR TKI during first line treatment within 28 days since the start date of chemotherapy, will be allowed to enter the study, in the absence of disease progression. Prior neoadjuvant/adjuvant cytotoxic chemotherapy is not allowed, unless the relapse occurred more than 12 months after the last administration of neoadjuvant/adjuvant chemotherapy
? cMET-amplification (GCN = 6) by FISH determined by a Novartis-designated central laboratory on a newly obtained tumor biopsy (preferred) or an archival tumor sample obtained at or any time after the progression on prior 1st or 2nd generation EGFR TKI
? EGFR-T790M negative status assessed from a biopsy or an archival tumor sample collected at or any time after the progression on prior 1st or 2nd generation EGFR TKI, determined locally by either Roche Cobas or Qiagen therascreen test or by a Novartis designated central laboratory
? Presence of at least one measurable lesion according to RECIST v1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation.
? Adequate organ function at screening including white blood cell count = 4 x 10^9/L and platelet count = 100 x 10^9/L
Common for Phase Ib and Phase II:
? = 18 years of age at the time of informed consent
? Locally advanced or metastatic NSCLC (stage IIIB and is not a candidate for definitive multimodality therapy or IV) other than predominantly squamous cell histology harboring EGFR mutation known to be associated with EGFR TKI drug sensitivity (exon 19 deletion or L858R).
? Must meet the criteria for acquired resistance to EGFR TKI (either 1st generation (e.g., erlotinib, gefitinib) or 2nd generation (e.g., afatinib)) defined as documented clinical benefit (CR, PR, or SD (= 6 months) as per RECIST) or demonstrated progression, while on continuous treatment, or within 30 days since the date of last administration of EGFR TKI, per RECIST
? Must have recovered from all toxicities related to prior anticancer therapies to grade = 1 (CTCAE v 4.03). Patients with any grade of alopecia are allowed to enter the study.
? Life expectancy = 3 months.
? ECOG performance status (PS) = 1.
? Adequate organ function at screening including:
? Hemoglobin = 9 g/dL
? Absolute neutrophil count (ANC) = 1.5 x 10^9/L
? Calculated creatinine clearance (using Cockcroft-Gault formula) = 45 mL/min
? Total bilirubin = 1.5 x ULN
? Aspartate transaminase (AST) = 3 x ULN, except for patients with liver metastasis, who may only be included if AST

Exclusion Criteria

Specific Phase II:
? History of severe hypersensitivity reaction to platinum containing drugs, pemetrexed or any known excipients of these drugs.
? Prior treatment with any of the following agents: crizotinib, or any other cMET inhibitor or HGF-targeting inhibitor, concomitant EGFR TKI and platinum based chemotherapy as first line regimen, platinum-based chemotherapy as first line treatment
Common for Phase Ib and Phase II:
? Known hypersensitivity to any of the excipients of INC280
? Prior treatment with any 3rd generation EGFR TKI (e.g., CO1686, AZD9192, EGF816).
? Symptomatic central nervous system (CNS) metastases
? Presence or history of carcinomatous meningitis
? 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)
? Thoracic radiotherapy to lung fields = 4 weeks prior to study enrollment or patients who have not recovered from radiotherapy-related toxicities
? Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years
? Presence of clinically significant ophthalmologic abnormalities
?Bullous and exfoliative skin disorders at baseline of any grade
?Presence or history of microangiopathic hemolytic anemia with thrombocytopenia
?Clinically significant, uncontrolled heart diseases and/or recent cardiac event (within 6 months prior to screening)
?Presence of acute or chronic pancreatitis, surgery of the pancreas, history of cystic fibrosis or any other factors that may increase the risk of pancreatitis
?Impairment of GI function or GI disease that may significantly alter the absorption of INC280 or erlotinib
?Previous anti-cancer and investigational agents within 4 weeks or = 5 x half-life of the agent (whichever is longer) before Cycle 1 Day 1. If previous treatment is a monoclonal antibody, then the treatment must be discontinued at least 4 weeks before Cycle 1 Day 1. If previous treatment is gefitinib, then the treatment must be discontinued at least 8 days before C1D1. If previous treatment is erlotinib or afatinib, the treatment must be discontinued at least 7 days prior to C1D1.
?Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior (2 weeks for resection of brain metastases) to study enrollment or who have not recovered from side effects of such procedure
?Patients receiving treatment with any enzyme-inducing anticonvulsant that cannot be discontinued at least 1 week before first dose of study treatment, and for the duration of the study. Patients on non-enzyme-inducing anticonvulsants are eligible
? Strong inhibitors or moderate inducers of CYP3A4; strong inducers of CYP3A4; strong inhibitors or strong inducers of CYP1A2; proton pump inhibitors, within 1 week prior to start of treatment with INC280 and for the duration of the study
? Pregnant or nursing (lactating) women

Please refer to protocol for further details and any additional exclusion criteria.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified