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Non-Small Cell Lung CancerPhase 1/2NCT07579221

Ph1/2 Trial Of Navlimetostat With Pumitamig In MTAP-Deficient Advanced Non-Small Cell Lung Cancer

A Phase 1/2 study testing Navlimetostat and Pumitamig in people with Non-Small Cell Lung Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The goal of this clinical research study is to find a safe and tolerable dose of navlimetostat in combination with pumitamig that can be given to patients with MTAP-deficient advanced non-small cell lung cancer (NSCLC). The effectiveness of the study drugs 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?
Navlimetostat and Pumitamig
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
16 Jul 2026to 1 Aug 2031
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

  • General inclusion criteria
  • Age ≥18 years. Because no dosing or adverse event data are currently available on the use of navlimetostat in combination with pumitamig in patients <18 years of age, children are excluded from this study.
  • Have at least one measurable lesion as the target lesion based on RECIST v1.1. Lesions treated with prior local treatment (radiation, ablation, etc) are generally not considered target lesions. If the lesion with prior local treatment is the only target lesion, evidence must be provided to demonstrate disease progression.
  • MTAP loss as defined by homozygous deletion on NGS and/or by absent MTAP protein expression by IHC. Test can be performed on an archival tissue. External testing by a commercial vendor (e.g. Foundation Medicine, Caris, BostonGene, Tempus) or internal assay (e.g. UT MD Anderson MAPP or IHC) is accepted.
  • ECOG performance status 0-1.
  • Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
Show all 36Show fewer
  • Patients must have previously received at least one course of systemic therapy for advanced or metastatic disease. Perioperative treatment is accepted if patient progresses within 6 months.
  • Patients must have received at least one prior line of standard therapy. Prior exposure to anti-PD-1 or anti-PD-L1 therapies or other checkpoint inhibitors is permitted.
  • Patients with actionable genomic alterations for which targeted therapy is considered standard front-line must have received appropriate targeted therapy EGFR, ALK, RET, NTRK, MET or ROS1). Patients may also have been treated with one or more lines of chemotherapy.
  • Adequate organ and marrow function as defined below
  • Hemoglobin ≥9.0 g/dL with no packed red blood cell transfusions in the past 7 days.
  • Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L.
  • Platelet count ≥100,000 with no platelet transfusions in the past 7 days.
  • Total bilirubin ≤1.5 x institutional upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is ≤3 × ULN.
  • AST (SGOT)/ALT (SGPT) <3 x institutional ULN value unless liver metastases are present, in which case <5 x ULN.
  • Calculated creatinine clearance ≥45 mL/min (using Cockroft-Gault formula or 24-hour urine collection).
  • Urine protein < 2+ or 24-hour urine protein quantification < 1.0 g
  • Coagulation function: international normalized ratio (INR) or prothrombin time and activated partial thromboplastin time ≤ 1.5 x ULN unless the participant is receiving anticoagulation therapy as long as the prothrombin or activated partial thromboplastin is within therapeutic range of intended use of anticoagulant.
  • Agree to follow the study protocol, including treatment, scheduled visits, and examinations, for the duration of the study.
  • Reproductive status
  • Note: The investigator or designee shall counsel individual of childbearing potential (IOCBP) participants (as defined in Appendix 3) and male (as assigned at birth) participants who are sexually active with IOCBP on the importance of pregnancy prevention, the implications of an unexpected pregnancy, and the potential of fetal toxicity occurring due to transmission of study intervention present in seminal fluid to a developing fetus, even if the participant has undergone a successful vasectomy or if the partner is pregnant.
  • Note: The investigator or designee shall evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. • Female (as assigned at birth) participants Note: Individuals who are not of childbearing potential are exempt from contraceptive requirements.
  • o IOCBP must have a negative highly sensitive urine or serum (as required by local regulation) pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study intervention.
  • Note: If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Note: The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to potentially decrease the risk for inclusion of an individual with an undetected pregnancy.
  • IOCBP participants must agree to follow instructions for method(s) of contraception as described below and included in the ICF.
  • IOCBP are not permitted to use hormonal contraceptive methods alone as a highly effective method of contraception and must use an additional nonhormonal highly effective method of contraception (as described in Appendix 3).
  • o A female (as assigned at birth) is eligible to participate if they are not pregnant or breastfeeding and at least 1 of the following conditions applies:
  • Is not an IOCBP OR
  • Is an IOCBP using a combination of a hormonal and a non-hormonal contraceptive method or a non-hormonal method alone that is highly effective (with a failure rate of < 1% per year), as described in Appendix 3, during the intervention period and for at least 6 months after the last dose of study intervention. IOCBP participants must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction for the same period. If needed, IOCBP participants should be advised to seek advice about egg donation and cryopreservation of germ cells before treatment.
  • Male (as assigned at birth) participants:
  • Note: Azoospermic males are not exempt from contraceptive requirements and will be required to always use a latex or other synthetic condom during any sexual activity (eg, vaginal, anal, oral) with IOCBP, even if the participant has undergone a successful vasectomy or if the partner is pregnant.
  • Male (as assigned at birth) participants will be required to always use a latex or other synthetic condom during any sexual activity (eg, vaginal, anal, oral) with IOCBP, even if the participant has undergone a successful vasectomy or if the partner is pregnant or breastfeeding. Male (as assigned at birth) participants should continue to use a condom during the intervention period and for at least 6 months after the last dose of study intervention.
  • IOCBP partners of male (as assigned at birth) participants should be advised to use a highly effective method of contraception during the intervention period and for at least 6 months after the last dose of study intervention for the male participant. IOCBP partners are not permitted to use hormonal contraceptive methods alone as a highly effective method of contraception and must use an additional non-hormonal highly effective method of contraception (as described in Appendix 3).
  • Male (as assigned at birth) participants with a pregnant or breastfeeding partner must agree to remain abstinent from sexual activity or use a male condom during any sexual activity (eg, vaginal, anal, oral), even if the participant has undergone a successful vasectomy, during the intervention period and for at least 6 months after the last dose of study intervention.
  • Male (as assigned at birth) participants must refrain from donating sperm during the intervention period and for at least 6 months after the last dose of study intervention. If needed, male (as assigned at birth) participants should be advised to seek advice about sperm donation and cryopreservation of germ cells before treatment.
  • Breastfeeding partners of male (as assigned at birth) participants should be advised to consult their health care provider about using appropriate highly effective contraception during the time the male participant is required to use condoms. • Ability to understand and willingness to sign a written informed consent document.

Who cannot join

  • Prior treatment with PRMT5 and/or MAT2A inhibitors.
  • Prior treatment with anti-PD-1/VEGF or anti-PD-L1/VEGF bispecific antibodies
  • Exposure to systemic anticancer therapy within 21 days or 5 half-lives (whichever is longer) prior to trial enrollment is not permitted.
  • Significant risk of pulmonary hemorrhage (per investigators clinical judgement) indicated by the following criteria:
  • Tumors with clear radiographic evidence of major blood vessel invasion, as demonstrated by any of the following radiological features: luminal irregularity, discontinuity, distortion or truncation, intraluminal mass formation or any other abnormal imaging funding assessed by the investigator to indicate risk of bleeding.
  • Tumor lesions with clear invasion of major airways (such as tracheal invasion) or vital organs (such as the heart, pericardium, and esophagus)
Show all 40Show fewer
  • At least one major cavitation posing hemorrhage risk
  • Clinically significant hemoptysis defined as coughing up or expelling ≥ 1 teaspoon (5 mL) of blood or small blood clots within 4 weeks prior to study treatment initiation. Note: participants with blood in the sputum are allowed to be enrolled.
  • Recent (within 3 months) history of intracranial/spinal or GI bleed, vascular disease with a risk of rupture, or therapeutic anticoagulation/antiplatelet treatment within 10 days before initiation of treatment. Participants receiving anticoagulation at a stable dose may be eligible if their PT and aPTT values are stable and within the intended therapeutic range, and if hemorrhagic risk is assessed as low per investigator's clinical judgement.
  • Have any of the following hypertension or diabetic conditions prior to trial treatment:
  • Uncontrolled hypertension (systolic BP ≥ 160mmHg and/or diastolic BP
  • ≥ 100mmHg) while on antihypertensive medication
  • Those with a history of hypertensive crisis or hypertensive encephalopathy
  • Poorly controlled diabetes (fasting blood glucose ≥ 13.3mmol/L / 240 mg/dL or HgA1c ≥ 8.5%)
  • Has a known additional malignancy that is progressing or requires active treatment.
  • Exceptions include basal cell carcinoma of the skin, ductal carcinoma in situ, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer. 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.
  • Major surgery within 21 days of starting treatment is not permitted. Patients must have recovered from the effects of any major surgery.
  • Patients with an average QTc (using Fridericia correction) >470 msec are excluded.
  • Patients with clinically significant uncontrolled medical conditions are excluded, including: active infection requiring IV antibiotics; significant cardiovascular disease (including uncontrolled hypertension or heart failure, ventricular arrythmia, unstable angina or MI within 6 mo prior to study treatment initiation); extensive bilateral interstitial lung disease; psychiatric illness that limits compliance; history GI/non-GI fistula, GI perforation, or intraabdominal abscess within 6 mo prior to initiation on study; evidence or history of bleeding diathesis or coagulopathy considered a safety risk as per investigatory clinical judgement including history of thromboembolic or major hemorrhagic events within 6 months of initiation on study; or any other condition deemed high risk by the Investigator.
  • Known central nervous system (CNS) metastases or leptomeningeal disease is exclusionary unless adequately treated and the patient is no longer on steroids or anticonvulsants. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
  • Patients unable to swallow oral medication or with gastrointestinal disorders likely to interfere with drug absorption are excluded.
  • Pregnant or breastfeeding women are excluded.
  • Ongoing need for a medication with a known risk of Torsade's de Pointes or known as a strong inhibitor or strong inducer of CYP3A4 and/or P-glycoprotein or a proton-pump inhibitor that cannot be switched to alternative treatment prior to study entry. The following drug interaction databases and other literature can be utilized to determine the CYP3A4/Pgp inhibitors and inducers:
  • o https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-anddruginteractions-table-substrates-inhibitors-and-inducers https://druginteractions.medicine.iu.edu/MainTable.aspx
  • Active viral hepatitis, including the following:
  • Any positive test result for hepatitis B virus (HBV) indicating presence of virus, e.g., HBV DNA positive would be excluded. Participants with negative HBV viral load are eligible to enroll, as are participants with anti-HBs positive in line with prior vaccination or resolved infection.
  • Any positive test result for hepatitis C virus (HCV) indicating presence of active viral replication (detectable HCV RNA).
  • Participants with positive HCV antibody and an undetectable HCV RNA are eligible to enroll.
  • Known human immunodeficiency virus (HIV) positive with an AIDS-defining opportunistic infection within the last year, or a current CD4 count < 350 cells/μL. Participants with HIV are eligible if they have received established antiretroviral therapy (ART) for at least 4 weeks prior to study treatment initiation and continue on ART as clinically indicated while enrolled on study. Viral serology only to be conducted if locally mandated and, if done, must be performed within 28 days of study treatment initiation.
  • Evidence of active infection that requires systemic antibacterial, antiviral, or antifungal therapy ≤ 7 days prior to the first dose of study intervention.
  • Live/attenuated vaccine received within 30 days of first treatment. The use of inactivated seasonal influenza vaccines (e.g., Fluzone®) will be permitted on study without restriction.
  • Any botanical preparation (e.g., herbal supplements or traditional Chinese medicines) intended to treat the disease under study within 2 weeks prior to treatment. The concurrent use of any botanical preparation is not permitted while on study.
  • Prior organ allograft.
  • History of allergy to study intervention or any of its components.
  • History of severe (Grade ≥3) irAEs observed with previous PD-1/PD-L1 checkpoint inhibitors that led to treatment discontinuation and rechallenge with ICI was not possible.
  • Active, known autoimmune disease. Note: participants with endocrine disorders treated with hormone replacement (e.g. Type I DM, hypothyroidism only requiring hormone replacement), skin disorders not requiring systemic therapy or conditions not expected to recur are allowed.
  • Advanced/clinically significant lung disease (e.g. pneumonitis requiring systemic steroids, uncontrolled COPD or asthma, restrictive lung disease or pulmonary hypertension) within 6 mo prior to study treatment initation, or any history of ILD or pneumonitis requiring treatment with systemic steroids (>/= G2), or who have current or suspected ILD or pneumonitis.
  • History of peripheral artery disease (e.g., claudication, Leo Beuerger's Disease).
  • Any condition for which, in the investigator's opinion, participation would not be in the patient's best interest (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
  • Participation in another interventional clinical tria

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Natalie Vokes Natalie Vokes, MD contact

(713) 745-1461

nvokes@mdanderson.org

United States1 site, 1 recruiting

  • UT MD Anderson

    Houston, Texas, 77090

    Natalie Vokes, MD

    Natalie Vokes, MD

    Recruiting

Other trials in United States

About this study

Official title: Phase 1/2 Trial Of Navlimetostat With Pumitamig, A PD-L1/VEGF Bispecific Fusion Protein, In MTAP-Deficient Advanced Non-Small Cell Lung Cancer

The goal of this clinical research study is to find a safe and tolerable dose of navlimetostat in combination with pumitamig that can be given to patients with MTAP-deficient advanced non-small cell lung cancer (NSCLC). The effectiveness of the study drugs will also be studied.

Read the detailed description

Primary Objectives:

Phase I: To evaluate the safety of navlimetostat in combination with pumitamig. Phase II: To evaluate the efficacy of navlimetostat in combination with pumitamig.

Secondary Objectives:

  • To evaluate toxicity and tolerability of navlimetostat in combination with pumitamig.
  • To evaluate efficacy outcomes including disease control rate, progression-free survival, overall survival, and duration of response.
  • To compare the efficacy of the combination in patients with prior ICI exposure and those without (treated with targeted therapy and/or chemotherapy).

Exploratory Objectives:

  • To identify potential biomarkers of resistance and sensitivity including MTAP expression (IHC), ctDNA changes as a predictive biomarker for detecting early progression and/or poor response to therapy, and early changes in cytokines and circulating immune cells as markers of treatment response
  • To investigate the TME in MTAP-deficient NSCLC before and after treatment
Being tested
Navlimetostat, Pumitamig
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.

  • NavlimetostatDrug

    Also called MRTX1719, BMS-986504

    Given orally once daily

  • PumitamigDrug

    Given by infusion

Study groups in NCT07579221
Study groupRoleWhat they receive
Phase 1 Safety Lead-In: Treatment with Navlimetostat + PumitamigExperimentalParticipants will receive treatment with the combination of navlimetostat, administered orally once daily (QD) combined with pumitamig, administered intravenously (IV) every 3 weeks (Q3W) in 21- day cycles until disease progression or treatment intolerance.
Receives: Drug: Navlimetostat; Drug: Pumitamig
Phase 2 Efficacy Evaluation: Treatment with Navlimetostat + PumitamigExperimentalParticipants will receive treatment with the combination of navlimetostat, administered orally once daily (QD) combined with pumitamig, administered intravenously (IV) every 3 weeks (Q3W) in 21- day cycles until disease progression or treatment intolerance.
Receives: Drug: Navlimetostat; Drug: Pumitamig

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and Adverse Events (AEs)

    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.

  1. First posted12 May 2026
  2. Study start16 Jul 2026
  3. Primary completion1 Aug 2029 (estimated)
  4. Study completion1 Aug 2031 (estimated)

Resources

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07579221
Sponsor's protocol ID
2026-0138
Other IDs
NCI-2026-03640
Status last verified
Sep 2026
First submitted
7 May 2026
Last updated
25 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Navlimetostat and Pumitamig 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 36 inclusion and 40 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: looking for participants now, as of the sponsor's last update on 25 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?

Contact Natalie Vokes Natalie Vokes, MD ((713) 745-1461, nvokes@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Adverse Events (AEs) (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?

On the ClinicalTrials.gov record for NCT07579221.

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 25 Sep 2026.

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