Non-small Cell Lung CancerPhase 1/2NCT06083857
PhI/II Study of Amivantamab and Tepotinib Combo in MET-altered Non-small Cell Lung Cancer
A Phase 1/2 study testing Amivantamab and Tepotinib in people with Non-small Cell Lung Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Amivantamab and Tepotinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jun 2024to 31 Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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])
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- 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.
- Hemoglobin ≥10 g/dL
- ANC ≥1.5 x 109 /L
- Platelets ≥75 x 10 9 /L
- AST and ALT ≤3 x ULN
- Total bilirubin ≤1.5 x ULN; subjects with Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits
- Serum creatinine <1.5 x ULN or if available, calculated or measured creatinine clearance >50 mL/min/1.73 m2 ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; ULN = upper limit of normal
- 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:
- Not of childbearing potential
- Of child-bearing potential and practicing true abstinence during the entire period of the study, including up to 6 months after the last dose of study treatment is given
- Of childbearing potential and practicing 2 methods of contraception, including 1 highly effective user independent method and a second method.
- 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.
Who cannot join
- 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:
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- 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:
- A medical history of deep vein thrombosis or pulmonary embolism within 1 month prior to first dose of study drug or any of the following within 6 months prior to the first dose of study drug: myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, uncontrolled hypertension, clinically significant cardiac arrythmia, or any acute coronary syndrome. Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, incidental or asymptomatic pulmonary embolism, are not exclusionary.
- 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.
- 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:
- Non-muscle invasive bladder cancer (NMIBC) treated within the last 24 months that is considered completely cured. b. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured. c. Non-invasive cervical cancer treated within the last 24 months that is considered completely cured.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the detailed description
Primary Objectives:
- For the safety run-in portion of the trial:
- To evaluate dose-limiting toxicity (DLT) and to establish the recommended phase II dose (RP2D) of amivantmab given in combination with tepotinib in patients with advanced MET-altered NSCLC. The primary endpoint is dose-limiting toxicity (DLT) and recommended phase 2 dose (RP2D).
- For the efficacy portion of the trial:
- To preliminarily assess efficacy of amivantamab + tepotinib combination in cohort A (MET exon 14 skipping TKI-naïve) , in terms of objective response rate.
Secondary Objectives
- Determine whether amivantamab + tepotinib improves objective response rate in each cohort (cohort B and cohort C)
- Determine whether amivantamab + tepotinib improves disease control rate (DCR) in each cohort
- Determine whether amivantamab + tepotinib improves Duration of Response (DoR) in each cohort
- Determine the safety and tolerability of amivantamab + tepotinib in each cohort
Exploratory Objectives
- Explore the association of baseline genomic profiles (from tumor, germline DNA, and ctDNA) with clinical benefit in patients treated with amivantamab + tepotinib
- Explore resistance mechanisms to amivantamab + tepotinib combination. At the time of progression, patients will undergo ctDNA genomic tests and a biopsy (optional). The purpose of this additional tissue acquisition is for molecular analysis and comparison with the initial specimen, to determine if there are changes in molecular alterations or pathways that shed light on mechanisms of resistance.
- Determine the immunomodulatory effects of amivantamab + tepotinib combination.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Amivantamab, Tepotinib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmivantamabDrug
Given by IV (vein)
TepotinibDrug
Given by PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Amivantamab; Drug: Tepotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: through study completion: an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2023
- Study start18 Jun 2024
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Xiuning Le, MD,PHD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06083857
- Sponsor's protocol ID
- 2022-0860
- Other IDs
- NCI-2023-08689
- Status last verified
- Sep 2026
- First submitted
- 9 Oct 2023
- Last updated
- 11 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT06083857
- Acronym / sponsor ID
- 2022-0860
- Conditions
- Non-small Cell Lung Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 3 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 18 Jun 2024 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 16 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To learn if the combination of amivantamab and tepotinib can help to control NSCLC. The safety of this drug combination will also be studied.
Detailed description
Primary Objectives:
- For the safety run-in portion of the trial:
- To evaluate dose-limiting toxicity (DLT) and to establish the recommended phase II dose (RP2D) of amivantmab given in combination with tepotinib in patients with advanced MET-altered NSCLC. The primary endpoint is dose-limiting toxicity (DLT) and recommended phase 2 dose (RP2D).
- For the efficacy portion of the trial:
- To preliminarily assess efficacy of amivantamab + tepotinib combination in cohort A (MET exon 14 skipping TKI-naïve) , in terms of objective response rate.
Secondary Objectives
- Determine whether amivantamab + tepotinib improves objective response rate in each cohort (cohort B and cohort C)
- Determine whether amivantamab + tepotinib improves disease control rate (DCR) in each cohort
- Determine whether amivantamab + tepotinib improves Duration of Response (DoR) in each cohort
- Determine the safety and tolerability of amivantamab + tepotinib in each cohort
Exploratory Objectives
- Explore the association of baseline genomic profiles (from tumor, germline DNA, and ctDNA) with clinical benefit in patients treated with amivantamab + tepotinib
- Explore resistance mechanisms to amivantamab + tepotinib combination. At the time of progression, patients will undergo ctDNA genomic tests and a biopsy (optional). The purpose of this additional tissue acquisition is for molecular analysis and comparison with the initial specimen, to determine if there are changes in molecular alterations or pathways that shed light on mechanisms of resistance.
- Determine the immunomodulatory effects of amivantamab + tepotinib combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Amivantamab and Tepotinib Combination | Experimental | Drug: Amivantamab, Drug: TepotinibParticipants will be given 2 investigational drugs (amivantamab and tepotinib) and come to the clinic for study visits every 4 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- 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:
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmivantamabGiven by IV (vein) | Drug | Amivantamab and Tepotinib Combination |
| TepotinibGiven by PO | Drug | Amivantamab and Tepotinib Combination |
Primary outcome
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Time frame: through study completion: an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2026.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiuning Le, MD,PHD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Amivantamab and Tepotinib in people with Non-small Cell Lung Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 (time frame: through study completion: an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2026.