Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion
Principal Investigator
by Edward B Garon (ucla)Mykola Onyshchenko (ucla)

Description

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.

Official Title

A Phase III Randomized, Controlled, Open-label, Multicenter, Global Study of Capmatinib in Combination With Osimertinib Versus Platinum - Pemetrexed Based Doublet Chemotherapy in Patients With Locally Advanced or Metastatic NSCLC Harboring EGFR Activating Mutations Who Have Progressed on Prior Generation EGFR-TKI Therapy and Whose Tumors Are T790M Mutation Negative and Harbor MET Amplification (GEOMETRY-E)

Details

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.

Keywords

Carcinoma, Non-Small-Cell Lung INC280 capmatinib osimertinib pemetrexed platinum-based chemotherapy NSCLC Non-Small Cell Lung Cancer Carcinoma EGFR Mutation T790M negative MET amplification second line therapy GEOMETRY GEOMETRY-E Carboplatin cisplatin

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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

You CAN'T join if...

  • 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
  • known druggable molecular alterations that may render participants eligible for alternative targeted therapies

Other protocol-defined inclusion/exclusion criteria may apply.

Locations

  • UCLA Santa Monica Hematology / Oncology accepting new patients
    Santa Monica California 90404 United States
  • University of California at Los Angeles accepting new patients
    Torrance California 90502 United States

Lead Scientists at UC Cancer

  • Edward B Garon (ucla)
    Professor, Medicine. Authored (or co-authored) 157 research publications
  • Mykola Onyshchenko (ucla)
    HS Assistant Clinical Professor, Medicine. Authored (or co-authored) 17 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Novartis Pharmaceuticals
ID
NCT04816214
Phase
Phase 3 research study
Study Type
Interventional
Participants
Expecting 245 study participants
Last Updated