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

Starting soon · Phase 1/Phase 2

Conditions studied: Non-Small Cell Lung Cancer

In brief

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.

Key facts

Study ID

NCT07579221

Run by

M.D. Anderson Cancer Center

People needed

17

Starts

2026-11-30

Expected to finish

2031-08-01

Last updated by the study team

2026-06-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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).
• 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.

You may not qualify if…

• 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)
• 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:

Where it is running

• UT MD Anderson — Houston, Texas, United States

Full record on ClinicalTrials.gov

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