An Open-Label Phase I/II Study to Evaluate the Safety and prelimiBasnary Efficacy of Amivantamab and Tepotinib Combination in MET-altered Non-small Cell Lung Cancer (NSCLC)
An Open-Label Phase I/II Study to Evaluate the Safety and prelimiBasnary Efficacy of Amivantamab and Tepotinib Combination in MET-altered Non-small Cell Lung Cancer (NSCLC)
To learn if the combination of amivantamab and tepotinib can help to control NSCLC. The safety of this drug combination will also be studied.
Primary Objectives:
Secondary Objectives
Exploratory Objectives
Inclusion Criteria:
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:
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.
A woman of childbearing potential must have a negative serum pregnancy test at screening and within 7 days of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study.
A woman must be compliant with the Contraceptive Guidance and Collection of Pregnancy Information:
Participant must agree to continue contraception throughout the study and through 6 months after the last dose of study treatment.
• Note: If the childbearing potential changes after start of the study (eg, woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) the woman must begin birth control, as described above.
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study treatment.
A man must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 6 months after receiving the last dose of study treatment. A man who is sexually active with a woman of childbearing potential must agree to use a condom with spermicidal foam/gel/film/cream/suppository and his partner must also be practicing a highly effective method of contraception (ie, established use of oral, injected, or implanted hormonal methods of contraception; placement of an intrauterine device [IUD] or intrauterine hormone-releasing system [IUS]).
If the participant is vasectomized, he must still use a condom (with or without spermicide) for prevention of passage of exposure through ejaculation, but his female partner is not required to use contraception.
A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of study treatment.
Participant must be willing and able to adhere to the lifestyle restrictions specified in this protocol.
Exclusion Criteria:
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:
Participant has active cardiovascular disease including, but not limited to:
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.
Immune-mediated rash from prior treatment that has not resolved prior to enrollment.
Any unresolved toxicities from prior therapy greater than CTCAE grade 1 (with the exception of alopecia grade 2) at the time of starting study treatment.
Participant has concurrent or prior malignancy other than the disease under study. The following exceptions require consultation with the Medical Monitor: