PhI/II Study of Amivantamab and Tepotinib Combo in MET-altered Non-small Cell Lung Cancer

NCT06083857 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2022-0860NCI-2023-08689
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if the combination of amivantamab and tepotinib can help to control NSCLC. The safety of this drug combination will also be studied.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion: an average of 1 year

Study Arms (1)

Amivantamab and Tepotinib Combination

EXPERIMENTAL

Participants will be given 2 investigational drugs (amivantamab and tepotinib) and come to the clinic for study visits every 4 weeks.

Drug: Amivantamab; Drug: Tepotinib

Interventions

Amivantamab DRUG

Given by IV (vein)

Amivantamab and Tepotinib Combination

Tepotinib DRUG

Given by PO

Amivantamab and Tepotinib Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health inf ormation prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• Histologically or cytologically confirmed non-small cell lung cancer.
• Locally advanced or metastatic disease, not amenable to curative surgery or radiotherapy.
• Patients must have one of the following:
• NSCLC which harbors MET Exon 14 skipping alterations detected in the tissue or ctDNA (safety cohort and cohort A \[MET ex14 TKI-naïve\] and B \[MET ex14 TKI-refractory\])
• MET gene amplification determined in tissue by next-generation sequencing (NGS) as copy-number gain (CNG\>=10) or FISH assay (MET:CEP7\>=2.0) (safety cohort and cohort C \[MET amplification or overexpression cohort\]
• MET gene amplification determined in ctDNA (definition of gain per ctDNA testing platform) (safety cohort and cohort C \[MET amplification or overexpression cohort\]
• MET overexpression by IHC 3+ (safety cohort and cohort C \[MET amplification or overexpression cohort\]
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Measurable disease per RECIST 1.1.
• Patients with brain metastases are eligible if they are asymptomatic, are treated, or are neurologically stable for at least two weeks without the use of steroids or on stable or decreasing dose of ≤ 15 mg daily prednisone (or equivalent).
• Ability to take pills by mouth.
• Previous treatment with cytotoxic chemotherapy or immunotherapy is allowed.
• Patients must have adequate bone marrow and organ functions.

You may not qualify if:

• For cohort A (METex14 TKI-naïve only), prior targeted therapy to c-MET is not allowed, which includes small molecule TKIs, such as tepotinib, capmatinib, savolitinib, or crizotinib. Prior amivantamab is also not allowed.
• Patients whose tumor harbors other oncogene-driver mutations, such as EGFR mutation, KRASG12C mutation, ALK-fusion, with prior targeted therapies, such as osimertinib, sotorasib, and other TKI, are not allowed.
• Positive hepatitis B (hepatitis B virus \[HBV\]) surface antigen (HBsAg) Note: Subjects with a prior history of HBV demonstrated by positive hepatitis B core antibody are eligible if they have at Screening 1) a negative HBsAg and 2) a HBV DNA (viral load) below the lower limit of quantification, per local testing. Subjects with a positive HBsAg due to recent vaccination are eligible if HBV DNA (viral load) is below the lower limit of quantification, per local testing.
• Positive hepatitis C antibody (anti-HCV). Note: Subjects with a prior history of HCV, who have completed antiviral treatment and have subsequently documented HCV RNA below the lower limit of quantification per local testing are eligible.
• Other clinically active or chronic liver disease.
• Participant is positive for human immunodeficiency virus (HIV), with 1 or more of the following:
• Receiving ART that may interfere with study treatment (consult with Principal Investigator for review of medication prior to enrollment)
• CD4 count \<350 at screening
• AIDS-defining opportunistic infection within 6 months of start of screening
• Not agreeing to start ART and be on ART\>4 weeks plus having HIV viral load \<400 copies/mL at end of 4-week period (to ensure ART is tolerated and HIV controlled).
• Participant has active cardiovascular disease including, but not limited to:
• Congestive heart failure (CHF), defined as New York Heart Association (NYHA) class III-IV or hospitalization for CHF (any NYHA class; refer to Appendix: New York Heart Association Criteria) within 6 months of study Day 1.
• Subject has uncontrolled inter-current illness, including but not limited to poorly controlled diabetes, ongoing or active infection (i.e., has discontinued all antibiotics for at least one week prior to first dose of study drug), or psychiatric illness/social situation that would limit compliance with study requirements. Subjects with medical conditions requiring chronic continuous oxygen therapy are excluded.
• Any ophthalmologic condition that is clinically unstable (consult with Principal Investigator for review of the condition prior to enrollment).
• Participant has an active or past medical history of ILD/pneumonitis, including drug-induced or radiation ILD/pneumonitis.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

amivantamab; tepotinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Marcelo Vailati Negrao, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2023
• First Posted: October 16, 2023
• Study Start: June 18, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

US (1)