First-in-Human Study of PLX-61639 in Locally Advanced or Metastatic Solid Tumors

NCT07284186 | Recruiting Phase 1 FDA Drug

• 1 other identifier: PLX-61639-101
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 10

Brief Summary

A multicenter, single-arm, first-in-human study to investigate the safety, pharmacokinetics, and preliminary antitumor activity of PLX-61639 in participants with locally advanced or metastatic, relapsed/refractory, SMARCA4-deficient solid tumors who are intolerant of or have failed available, approved therapies. The study will be conducted in 3 parts: dose escalation (Part 1), dose optimization (Part 2), and cohort expansion (Part 3). Each part of the study will consist of a Screening Phase lasting up to 28 days during which participants will be assessed for eligibility, a Treatment Phase beginning on Cycle 1 Day 1 and consisting of consecutive 28-day cycles, an End of Treatment Visit, and a Post-Treatment Follow-Up Phase. Participants will receive their assigned dose of PLX-61639 administered orally, once daily until progression/relapse, intolerance, death, or withdrawal from study treatment by the Investigator or participant.

Conditions

Gastric Adenocarcinoma; Metastatic Solid Tumor; Gastric Squamous Cell Carcinoma; SMARCA4 Mutation; Advanced Solid Tumor; Esophageal Squamous Cell Carcinoma; Gastroesophageal Junction (GEJ) Adenocarcinoma; Non-Small Cell Lung Carcinoma; Esophageal Adenocarcinoma; Gastroesophageal Junction Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Treatment Emergent Adverse Events

  From enrollment to 28 days after the last dose of PLX-61639

• Dose-Limiting Toxicities

  From enrollment to 28 days after first dose of PLX-61639

Secondary Outcomes (9)

• Dose reductions due to Adverse Events

  From Day 1 to the end of PLX-61639 treatment, an average of 1 year

• Study treatment discontinuations for reasons other than disease progression

  From Day 1 to the end of PLX-61639 treatment, an average of 1 year

• Pharmacokinetics of PLX-61639: Cmax

  From Day 1 to Day 15 of Cycle 1 (Part 1 only) (each cycle is 28 days)

• Pharmacokinetics of PLX-61639: Tmax

  From Day 1 to Day 15 of Cycle 1 (Part 1 only) (each cycle is 28 days)

• Pharmacokinetics of PLX-61639: AUC0-last

  From Day 1 to Day 16 of Cycle 1 (Part 1 only) (each cycle is 28 days)

Study Arms (1)

PLX-61639

EXPERIMENTAL

Drug: PLX-61639

Interventions

PLX-61639 DRUG

Orally available degrader of SMARCA2

PLX-61639

Eligibility Criteria

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

You may qualify if:

• Participants with locally advanced or metastatic, relapsed/refractory, solid tumors harboring a SMARCA4 loss-of-function mutation that have progressed on, are intolerant of, or not otherwise candidates for available approved therapies
• Adequate liver bone marrow, coagulation, renal, and cardiopulmonary function
• Measurable disease per RECIST 1.1
• ECOG PS of 0 or 1

You may not qualify if:

• Germline SMARCA4 mutations
• Known SMARCA2 mutation or loss of expression
• Symptomatic CNS disease
• Prior treatment with another SMARCA2-directed therapy
• History of other malignancies
• Clinically significant heart disease
• Uncontrolled hypertension
• Prolongation of QT interval

Sponsors & Collaborators

• Plexium, Inc.: lead

Study Sites (10)

Research Site

Scottsdale, Arizona, 85258, United States

RECRUITING

Research Site

Duarte, California, 91010, United States

RECRUITING

Research Site

Orange, California, 92868, United States

RECRUITING

Research Site

Boston, Massachusetts, 02114, United States

RECRUITING

Research Site

St Louis, Missouri, 63110, United States

RECRUITING

Research Site

New York, New York, 10044, United States

RECRUITING

Research Site

Durham, North Carolina, 27710, United States

RECRUITING

Research Site

Cleveland, Ohio, 44106, United States

RECRUITING

Research Site

San Antonio, Texas, 78229, United States

RECRUITING

Research Site

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma; Adenocarcinoma; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma Of Esophagus

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Chief Medical Officer

  Plexium, Inc.

  STUDY DIRECTOR

Central Study Contacts

Clinical Operations

CONTACT

619-631-3091; ClinicalTrials@Plexium.com

Study Design

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

Model Details: In Part 1, eligible participants will enroll sequentially in up to 5 escalating PLX-61639 dose cohorts. In Part 2, participants will be randomized 1:1 to 1 of 2 dose levels at or below the maximally tolerated (or administered) dose evaluated during Part 1. In Part 3, additional participants will enroll sequentially to 1 dose level selected from Part 2.

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 16, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): September 1, 2030
• Last Updated: June 12, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)