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)

  • End date
    Apr 15, 2027
  • participants needed
  • sponsor
    Novartis Pharmaceuticals
Updated on 24 May 2022
systemic therapy
measurable disease
growth factor
epidermal growth factor receptor
cancer chemotherapy
epidermal growth factor
lung carcinoma
egfr t790m


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.


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.

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


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
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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact



Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note