Study Evaluating Efficacy and Safety of Capmatinib in Combination With Osimertinib in Adult Subjects With Non-small Cell Lung Cancers as Second Line Therapy (GEOMETRY-E)

  • STATUS
    Recruiting
  • End date
    Apr 15, 2027
  • participants needed
    245
  • sponsor
    Novartis Pharmaceuticals
Updated on 24 May 2022
tyrosine
systemic therapy
measurable disease
growth factor
pemetrexed
carboplatin
epidermal growth factor receptor
EGFR
cancer chemotherapy
epidermal growth factor
osimertinib
lung carcinoma
egfr t790m

Summary

This phase III study is designed to evaluate the anticancer activity of capmatinib in combination with osimertinib compared to platinum-pemetrexed based doublet chemotherapy as second line treatment in patients with advanced or metastatic non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, T790M negative, mesenchymal-to-epithelial transition factor (MET) amplified who progressed following EGFR tyrosine kinase inhibitors (TKIs). The randomized part will be preceded by a safety run-in part in which the recommended dose of the combination of capmatinib and osimertinib will be confirmed.

Description

This is a multicenter, open-label, randomized, active-controlled, global phase III study that will enroll adult participants with locally advanced or metastatic NSCLC with EGFR activating mutation, T790M negative, MET amplified who have progressed following EGFR TKIs.

The study will consist of an initial safety run-in part to evaluate the safety and tolerability of capmatinib in combination with osimertinib and to confirm the recommended dose for the randomized part, and a randomized part that will evaluate the efficacy and safety of capmatinib in combination with osimertinib compared to platinum (cisplatin or carboplatin) - pemetrexed doublet based chemotherapy as second line treatment.

Participant's respective treatment (either with capmatinib in combination with osimertinib, or with platinum (cisplatin or carboplatin) - pemetrexed based doublet chemotherapy) will be continued until participant experiences any of the following: documented disease progression by Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1) (as assessed by the investigator in the run-in part, and as assessed by the investigator confirmed by blinded independent review committee (BIRC) in the randomization part), withdrawal of consent, pregnancy, lost to follow-up, or death. Participants who progressed in the platinum-pemetrexed arm will be allowed to crossover to capmatinib in combination with osimertinib therapy after BIRC confirmed, RECIST 1.1-defined progressive disease. Study treatment may be continued beyond initial disease progression as per RECIST 1.1 if, in the judgement of the investigator, there is evidence of clinical benefit, and the participant wishes to continue on the study treatment.

After treatment discontinuation, all participants will be followed for safety evaluations during the safety follow-up period.

Details
Condition Carcinoma, Non-Small-Cell Lung
Treatment cisplatin, carboplatin, Pemetrexed, Osimertinib, capmatinib
Clinical Study IdentifierNCT04816214
SponsorNovartis Pharmaceuticals
Last Modified on24 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Histologically or cytologically confirmed diagnosis of NSCLC with EGFR mutations known to be associated with EGFR TKI sensitivity, EGFR T790M negative and MET gene amplification
Stage IIIB/IIIC or IV NSCLC
Patients must have progressed on one prior line of therapy (1st/2nd generation EGFR TKIs, osimertinib or other third generation EGFR TKIs) for advanced/metastatic disease (stage IIIB/IIIC and must be candidates for platinum (cisplatin or carboplatin) - pemetrexed doublet based chemotherapy
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
Participants must have recovered from all toxicities related to prior systemic therapy to grade ≤ 1 Common Terminology Criteria Adverse Event 5.0 (CTCAE v 5.0)
At least one measurable lesion as defined by RECIST 1.1

Exclusion Criteria

Prior treatment with any MET inhibitor or HGF-targeting therapy
Participants 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
Carcinomatous meningitis
Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years
Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis
Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome
Clinically significant, uncontrolled heart diseases
Other protocol-defined inclusion/exclusion criteria may apply
known druggable molecular alterations that may render participants eligible for alternative targeted therapies
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