MTX-531-001 Phase 1 Study in Advanced Solid Tumors

This is a first-in-human, Phase 1, open-label study evaluating MTX-531, an investigational dual EGFR/PI3K inhibitor, in adults with advanced solid tumors. The study will evaluate the safety and tolerability of MTX-531, determine the maximum tolerated dose and recommended Phase 2 dose, and assess how the drug is processed by the body and its preliminary anti-tumor activity.

Inclusion Criteria: Age 1. Age ≥18 years at the time of signing the informed consent. Disease Characteristics 2. Has one of the following types of advanced or refractory solid tumor malignancy: EC - No specific requirement 1. FIGO stage III or IV (unresectable, recurrent, or metastatic disease) at study entry 2. Received 1, 2, or 3 prior systemic regimens in any setting that must include: i. Anti-PD(L)1 in any setting (unless contraindicated) ii. A platinum-containing chemotherapy in any setting c. Adjuvant/neoadjuvant chemotherapy with or without additional anti-cancer therapy will not count as a prior regimen in the absence of recurrence during or within 6 months of completion of the last dose of planned therapy. MBC - No specific requirement 1. Advanced or metastatic disease at the time of entry 2. HER2 negative according to American Society of Clinical Oncology/College of American Pathologists guidelines, defined as a HER2 IHC score of 0 or 1+, or an IHC score of 2+ accompanied by a negative fluorescence, chromogenic, or silver in situ hybridization test indicating the absence of HER2 gene amplification, or a HER2/CEP17 ratio of \50% as per echocardiography or multi-gated acquisition scan. 8. Baseline QTc interval ≤470 msec using Fridericia's QT correction formula. Note: This criterion does not apply to participants with right or left bundle branch block or on pacemakers, but prior discussion with the Medical Monitor is required. Clinical Laboratory Values 9. HbA1c \3000/mm3 * ANC \>1500/mm3 * Liver Function * Total bilirubin ≤1.5 × ULN * AST ≤2.5 × ULN; ALT ≤2.5 × ULN (AST, ALT ≤5 × ULN if liver metastases are present) * Coagulation * INR ≤1.5; aPTT ≤1.5 × ULN in the absence of anticoagulant therapy or within acceptable parameters per local standard of care on anticoagulant therapy. * Renal Function * Creatinine clearance ≥60 mL/min either measured or calculated using standard Cockcroft-Gault formula. * Albumin ≥3.0 g/dL Prior Therapy 11. Recovered to ≤Grade 1 toxicity from previous therapies, excluding alopecia, peripheral neuropathy, lymphopenia or therapy-related hypothyroidism or other endocrine disorders that are well controlled. 12. Demonstrated progressive disease or intolerance to the last regimen. Sex and Contraceptive/Barrier Requirements 13. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 1. Male Participants: Participants are eligible to participate if they agree to the following during the study intervention period and for at least 180 days after the last dose of study intervention: • Refrain from donating sperm PLUS, either: • Be abstinent from intercourse where pregnancy can occur (abstinent on a long term and persistent basis) and agree to remain abstinent OR • Must agree to use \[contraception /barrier\] as detailed below: Agree to use an external condom and with child-bearing potential (CBP) partner use an additional highly effective contraceptive method with a failure rate of \