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

NCT07579221 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2026-0138NCI-2026-03640
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (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

  Through study completion; an average of 1 year

Study Arms (2)

Phase 1 Safety Lead-In: Treatment with Navlimetostat + Pumitamig

EXPERIMENTAL

Participants 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.

Drug: Navlimetostat; Drug: Pumitamig

Phase 2 Efficacy Evaluation: Treatment with Navlimetostat + Pumitamig

EXPERIMENTAL

Participants 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.

Drug: Navlimetostat; Drug: Pumitamig

Interventions

Navlimetostat DRUG

Given orally once daily

Also known as: MRTX1719, BMS-986504

Phase 1 Safety Lead-In: Treatment with Navlimetostat + Pumitamig; Phase 2 Efficacy Evaluation: Treatment with Navlimetostat + Pumitamig

Pumitamig DRUG

Given by infusion

Phase 1 Safety Lead-In: Treatment with Navlimetostat + Pumitamig; Phase 2 Efficacy Evaluation: Treatment with Navlimetostat + Pumitamig

Eligibility Criteria

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

You may qualify if:

• 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).

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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

UT MD Anderson

Houston, Texas, 77090, United States

Location

Related Links

• UT MD Anderson Website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

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

• Natalie Vokes, MD

  UT MD Anderson

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natalie Vokes Natalie Vokes, MD

CONTACT

(713) 745-1461; nvokes@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: May 7, 2026
• First Posted: May 12, 2026
• Study Start (Estimated): November 30, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2031
• Last Updated: May 12, 2026

Record last verified: 2026-05

Locations

US (1)