Advanced Solid Tumor, Esophageal Adenocarcinoma, Esophageal Squamous Cell Carcinoma, Gastric Adenocarcinoma, Gastric Squamous Cell Carcinoma, Gastroesophageal Junction (GEJ) Adenocarcinoma, Gastroesophageal Junction Squamous Cell Carcinoma, Metastatic Solid Tumor, Non-Small Cell Lung Carcinoma, SMARCA4 Mutation
Conditions
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.
Interventions
DRUGPLX-61639
Orally available degrader of SMARCA2
Sponsors
Plexium, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * 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 Key
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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) |
| Radiographic response to PLX-61639 | From Day 1 to the end of PLX-61639 treatment, an average of 1 year |
| Time to response (TTR) to PLX-61639 | From Day 1 to achievement of partial or complete response, up to 24 weeks |
| Duration of response (DoR) to PLX-61639 | From first documented partial or complete response to disease progression or death, an average of 1 year |
| Progression Free Survival (PFS) of PLX-61639 | From Day 1 to disease progression or death, an average of 1 year |
Countries
United States
Contacts
CONTACTClinical Operations
STUDY_DIRECTORChief Medical Officer
Plexium, Inc.
Outcome results
None listed