RecruitingPhase 1

A Study of Tepotinib and Ivonescimab in People With Non-Small Cell Lung Cancer

A Pilot Study of Tepotinib + Ivonescimab in Patients With Advanced METex14 Skipping Positive NSCLC

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests tepotinib with ivonescimab for adults with advanced or returning non-small cell lung cancer that has a gene change called MET exon 14 skipping. Researchers will test up to two doses of tepotinib to find a dose that works well with few or mild side effects.

The researchers are doing this study to find out whether the combination of tepotinib and ivonescimab is a safe and effective treatment for people with non-small cell lung cancer (NSCLC) that is positive for METex14 skipping. The researchers will test up to two different doses of tepotinib in combination with ivonescimab to find the best dose of tepotinib that causes few or mild side effects in participants.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be age 18 or older.
  • Have non-small cell lung cancer confirmed by a tissue test, with MET exon 14 skipping confirmed by an approved lab test.
  • Have cancer that has returned, is stage IV, or is stage IIIB/C that cannot be treated with surgery or radiation.
  • Have cancer that can be measured on scans.
  • Be able to care for yourself and be out of bed or a chair for at least half of your waking hours.
  • Meet the study’s blood cell, kidney, liver, and blood-clotting test requirements.
  • If you had earlier cancer treatment, your cancer must have worsened on the most recent treatment. Earlier MET-targeted treatment or immune therapy is allowed.
  • If you or your partner could become pregnant, follow the study’s birth control rules. People who could become pregnant must have a negative blood pregnancy test.

Who can't join

  • Are pregnant or breastfeeding, or have an allergy to either study drug, its ingredients, or similar drugs.
  • Have another cancer gene change that can be targeted with treatment, such as EGFR, ALK, or ROS1.
  • Have cancer in the brain or its lining, unless it meets the study’s treatment and symptom-control rules. Brain tumors needing focused radiation must be treated.
  • Previously took drugs that block blood vessel growth, such as bevacizumab or ramucirumab; had whole-body cancer treatment within 21 days; or had radiation within 7 days of starting study treatment.
  • Have a history of lung tissue disease needing steroids, certain active immune system or lung diseases needing treatment, or inflammatory bowel disease, such as Crohn’s disease.
  • Have poorly controlled blood pressure, certain recent serious heart problems, blood clots, stroke, or major bleeding risks. Cancer growing into major blood vessels or organs also rules you out.
  • Have certain serious gut problems within 6 months, such as severe ulcers, bleeding, wounds that do not heal, or abnormal openings between organs.
  • Have a recent severe infection or an active infection needing whole-body treatment, with some exceptions for hepatitis treatment. Active hepatitis C is not allowed; HIV and hepatitis B must meet the study’s treatment and virus-control rules.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Criteria: * Documentation of Disease * Patients must have pathologically confirmed non-small cell lung cancer. This includes, but is not limited, to histologies such as adenocarcinoma, squamous cell carcinoma, sarcomatoid carcinoma, and poorly differentiated carcinoma. * Patients must have documentation of MET exon 14 skipping present in their cancer using an FDA-approved assay done within a laboratory with CLIA, ISO/IEC, CAP, or similar certification. * Definition of Disease * Patients must have advanced or recurrent disease. * Advanced disease is defined as stage IV disease or stage IIIB/C disease not amenable to local therapy such as radiation or surgery. * Patients must have measurable disease as defined by RECIST 1.1 criteria. * Must not have other known actionable oncogenic alterations, such as (but not limited to) EGFR sensitizing mutations, EGFR T790M mutation, ALK gene fusion, ROS1 gene rearrangement, RET gene rearrangement, NTRK rearrangement, HER2 mutation, KRAS activating mutations, and BRAF V600E mutation. * Must not have leptomeningeal disease or brain metastases unless: 1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 3 days following the stereotactic radiation and/or 14 days following whole brain radiation, and prior to sub-study randomization, AND 2) participant has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to start of study therapy. * Small/asymptomatic brain metastasis for which stereotactic radiation is indicated must be treated. * Prior Treatment * No prior angiogenesis inhibitor therapy (i.e. bevacizumab or ramucirumab) * Patients can have received prior MET inhibitor therapy * Patients can have received prior ICI therapy. * If applicable, patients must have progressed on their most recent line of therapy. * Must have not had prior systemic therapy within 21 days of the start of protocol therapy * Must not have received radiation therapy within 7 days of starting protocol therapy * Age ≥ 18 * ECOG Performance Status of ≤ 2 * Not Pregnant and Not Nursing * Female patients of childbearing age must have negative serum pregnancy test results before randomization. * Female patient of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 90 days after the last dose of ivonescimab or until 1 week after last dose of tepotinib (whichever is longer). * Unsterilized male patient having sex with a female partner of childbearing potential must agree to use an effective method of contraception from the beginning of screening until Day 90 after the last dose of ivonescimab * Required Organ Function * Adequate hematologic function defined as follows: * Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 * Platelets ≥ 100,000 cells/mm3 * Hemoglobin ≥ 9 g/d * Adequate renal function defined as follows: * Creatinine clearance (CrCL) of ≥50 mL/min by the Cockcroft-Gault formula or estimated glomerular filtration rate (eGFR) value ≥ 50 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (adjustment by BSA is not required for eGFR) * Urine protein \< 2+ or 24-hour urine protein \< 1.0g * Adequate hepatic function defined as follows: * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x ULN may be enrolled) * AST and ALT ≤2.5x institutional ULN. For patients with liver metastases, AST and ALT ≤ 5 x ULN. * Coagulation: PT or INR ≤ 1.5 ULN, and PTT or aPTT ≤ 1.5 x ULN (unless abnormalities are unrelated to coagulopathy or prophylactic anticoagulation) * Comorbid Conditions No history of interstitial lung disease requiring steroid treatment * Prior history of Grade ≥3 irAE * Must not have evidence of major blood vessel invasion or tumor invading into organs or risk of esophagotracheal or esophagopleural fistula Must not have active autoimmune or lung disease requiring systemic therapy (prednisone ≤ 10mg allowed) within 2 years of treatment * Poorly controlled hypertension with repeated systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≤ 100 mmHg after oral antihypertensive therapy * Severe infection within 4 weeks prior to randomization, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; active infection (as determined by the investigator) requiring systemic anti-infective therapy within 2 weeks prior to randomization (excluding antiviral therapy for hepatitis B or C) * Active or prior history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea) * Must not have a history of unstable angina, MI, CHF (NYHA grade ≥ 2) requiring hospitalization in the preceding 6 months * Must not have a history of gastric or esophageal varices, severe ulcers, or wounds that do not heal, or fistulas, or abscesses, or acute GI bleeding within 6 months of therapy * Must not have a history of arterial thromboembolic event, venous thromboembolic event grade ≥ 3, CVA/TIA, HTN crisis or HTN encephalopathy within 6 months of therapy * Must not have a history of bleeding tendencies or coagulopathy or clinically significant bleeding symptoms or risk within 4 weeks of therapy * Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots) * Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed. * Nasal bleeding /epistaxis (bloody nasal discharge is allowed) * Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to randomization is not allowed. The use of full-dose anticoagulants is permitted as long as the international normalized ratio (INR) or activated partial thromboplastin time (aPTT) is within therapeutic limits according to the medical standard of the enrolling institution. * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. * For patients with known HIV, HBV, and/or HCV infection: * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. * Patients with active hepatitis B are required to have stable or declining levels of hepatitis B DNA by polymerase chain reaction (PCR) on appropriate anti-viral therapy with acceptable tolerability for one month prior to randomization. * All patients with active hepatitis C (hepatitis C virus \[HCV\] antibody positive with HCV RNA levels above the lower limit of detection) are excluded. * Allergies o No history of allergic reaction to the study agent(s), compounds of similar chemical or biologic composition to the study agent (s) (or any of its excipients).

Study sites (7)

NJ

NY