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

NCT07874880 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: MTX-531-001
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumors (Phase 1); HNSCC; Endometrial Cancer; Her2-negative Metastatic Breast Cancer; Pan-RAS and BRAF Wild-type Advanced; Metastatic Colorectal Cancer (CRC); Head and Neck Squamous Cell Carcinoma

Keywords

Solid Tumors; HNSCC; Endometrial Cancer; Her2-negative metastatic breast cancer; Pan-RAS; BRAF wild-type advanced; Metastatic Colorectal Cancer (CRC); First-in-human; Phase 1 Solid Tumor; Phase 1; MTX-531; head and neck squamous cell carcinoma

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability profile of MTX-531

  To characterize the safety and tolerability profile of MTX-531 and to determine the MTD in participants with select advanced solid tumors.

  From the time of first dose of study drug administration up to 21 days.

• Provisional RP2D For Further Evaluation of MTX-531

  To determine the provisional RP2D for further evaluation of MTX-531

  From the time of first dose of study drug administration to 30 days after the last dose

Secondary Outcomes (2)

• Evaluation of the Preliminary Clinical Activity of MTX-531

  Up to 30 days after the last dose

• Assessment of MTX-531's PK Profile

  Up to the end of the last study drug administration

Study Arms (1)

MTX-531 Monotherapy

EXPERIMENTAL

Participants receive MTX-531 as monotherapy in sequential dose levels to evaluate the safety and tolerability of MTX-531, determine the maximum tolerated dose and recommended Phase 2 dose, and assess pharmacokinetics and preliminary clinical activity.

Drug: MTX-531

Interventions

MTX-531 DRUG

MTX-531 is an investigational small-molecule dual EGFR/PI3K inhibitor administered as monotherapy in adults with advanced solid tumors. Dose levels will be evaluated during dose escalation to assess safety, tolerability, pharmacokinetics, and preliminary clinical activity.

MTX-531 Monotherapy

Eligibility Criteria

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

You may qualify if:

• Age
• Age ≥18 years at the time of signing the informed consent.
• Disease Characteristics
• Has one of the following types of advanced or refractory solid tumor malignancy:
• EC - No specific requirement
• FIGO stage III or IV (unresectable, recurrent, or metastatic disease) at study entry
• 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
• Advanced or metastatic disease at the time of entry
• 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 \<2.0 based on the most recent tumor biopsy and assessed locally.
• Refractory to or relapsed after at 2, 3, 4, or 5, prior systemic regimens for metastatic disease, including (unless contraindicated):
• i. At least 1 cytotoxic chemotherapy regimen (as single agent or combination) in any setting.
• ii. At least 1 anticancer hormonal treatment in any setting. iii. At least 1 cyclin-dependent kinase inhibitor 4/6 in any setting. iv. Other treatments (eg, antibody-drug conjugates, PI3K pathway inhibitors) are allowed as long as the number of prior lines of therapy is not exceeded.
• d. Participants with bone-only metastases are excluded unless antitumor activity can be assessed using elevated baseline clinical tumor markers (eg, CA15-3, CA 27-29, CEA), or ctDNA.

You may not qualify if:

• Medical Conditions
• History (within 2 years before screening) of a malignancy that is histologically distinct from the cancers being studied with the exception of adequately treated basal cell or squamous cell skin cancers and/or ductal carcinoma in situ of the breast or other malignancies that have a very low potential for recurrence or for confounding study results.
• Symptomatic brain metastases requiring steroids or other interventions. Participants with previously diagnosed brain metastases are eligible if treatment has been completed and the participant has recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 2 weeks before the first dose of MTX-531, and are neurologically stable.
• Known leptomeningeal metastases.
• Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association), myocardial infarction within the last 6 months, unstable arrhythmias, unstable angina or other poorly controlled cardiac conditions (eg, arrhythmias) that are considered significant by the Investigator.
• Poorly controlled diabetes mellitus (including prior HbA1c measurements or compliance).
• Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection requiring IV antibiotics.
• Experienced prior Grade 3-4 toxicities or severe toxicities from PI3K or EGFR inhibitors.
• Any other medical condition (eg, pulmonary, psychiatric, neurological, significant dermatologic conditions that may confound the interpretation of on-treatment toxicities or life-threatening toxicities from prior PI3K- or EGFR-directed therapies, if applicable) that in the opinion of the Investigator would place the participant at unacceptably high risk for toxicity.
• Prior/Concomitant Therapy
• Received systemic or local anticancer therapy within 3 weeks before the first dose of MTX-531 or 5 half-lives of the drug (whichever is less).
• Received radiotherapy within 2 weeks before the first dose of MTX-531 and has not recovered from all radiation-related toxicities. A 1-week washout is allowed for palliative radiation (≤2 weeks of treatment course) to non-CNS tumors. Inability to swallow oral medications or impaired gastrointestinal absorption due to anomalies of the gastrointestinal tract, such as gastrectomy or active inflammatory bowel disease.(Administration of oral medications via feeding tubes is not allowed.)
• Any condition requiring chronic administration of \>10 mg daily prednisone or equivalent or other immunomodulators.
• Unable or unwilling to discontinue prohibited concomitant medications or adhere to restrictions for use of concomitant medications as defined in the protocol (see Section 6.9.2).
• Pregnant or nursing women

Sponsors & Collaborators

• MEKanistic Therapeutics, Inc.: lead
• Translational Drug Development: collaborator

Study Sites (1)

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Endometrial Neoplasms; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

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

Model Details: Participants receive MTX-531 as monotherapy in sequential dose levels to evaluate safety, tolerability, pharmacokinetics, and preliminary clinical activity.

Study Record Dates

• First Submitted: October 7, 2026
• First Posted: October 15, 2026
• Study Start (Estimated): October 20, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): September 29, 2029
• Last Updated: October 15, 2026

Record last verified: 2026-10

Locations

US (1)