A Randomized Phase II Study of Tepotinib with or Without Ramucirumab in Participants with MET Exon 14 Skipping Positive Stage IV or Recurrent Non-Small Cell Lung Cancer (Lung-MAP Sub-Study)

- Stage IV or recurrent NSCLC
- Measurable disease must be assessed (documented by CT or MRI) within 28 days prior to randomization to S1900K
- Non-measurable disease must be assessed within 42 days prior to randomization.
- Must have received at least one line of therapy for Stage IV or recurrent NSCLC and must have progressed (in opinion of treating physician) after the most recent line of therapy.
- Must not have received systemic therapy within 21 days prior to randomization.
- Must have fully recovered (</= Grade 1) from any side effects of prior therapy (except alopecia and vitiligo).
- Must not have had major surgery within 14 days prior to randomization and must have fully recovered from the effects of prior surgery.
- No radiation therapy within 7 days prior to randomization with exception of:
- Stereotactic radiation for CNS metastases (must be completed at least 3 days prior to randomization) and
Palliative radiotherapy to bone metastases must be completed at least 1 day prior to randomization.
- Documented MET exon 14 skipping mutation by either:
LungMAP screening, or
If outside of study: tissue or blood-based (ctDNA) NGS assay performed by a certified laboratory (CLIA, ISO/IED, CAP or similar)) (See LUNGMAP Protocol Sections 5.1c and 18.8).
- Must have a CT or MRI to evaluate for CNS disease within 42 days prior to randomization to S1900K.
- No leptomeningeal disease or spinal cord compression, unless:
Metastases have been locally treated and remained clinically controlled and asymptomatic for at least 3 days following stereotactic radiation and/or 14 days following whole brain radiation (and prior to substudy randomization), AND
Pt. has no residual neurological dysfunction and hass been off corticosteroids for at least 24 hours prior to sub-study randomization.
- No other known actionable oncogenic alterations.
- No prior MET inhibitor or angiogenesis inhibitor therapies.
- No history of interstitial lung disease that required steroid treatment.
- Zubrod PS of 0-1 within 28 days prior to randomization.
Must have adequate organ and marrow function as defined in Protocol Section 5.3.
- No cirrhosis at a level Child-Pugh B (or worse) OR any degree of cirrhosis AND a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis.
- Must have adequate cardiac function (NYHA Class 2B or better). No uncontrolled blood pressure or hypertension within 28 days prior to randomization. No arterial thromboembolic events within 6 months prior to randomization. No peripheral edema (Grade >0) within 28 days prior to randomization.
- Must have a complete medical history and physical exam, cystatin C test, and Lymphoscintigraphy scan within 28 days prior to randomization.