A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT3789 in Participants With Select Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation

This is an open-label, multi-center, dose-escalation, first in human, Phase 1 study of PRT3789, a SMARCA2 degrader, evaluating participants with selected advanced or metastatic solid tumors with loss of SMARCA4 due to truncating mutation and/or deletion. The study will evaluate escalating doses of PRT3789 until the MTD or RP2D is determined. Taking into account pharmacokinetic and pharmacodynamic data from the preceding dose levels, the dose may be escalated until a dose limiting toxicity is identified. Approximately 86 participants will be enrolled in dose escalation and backfill cohorts.

Inclusion Criteria:

• Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations (including contraception requirements), and other study procedures
• Histologically confirmed advanced, recurrent, or metastatic solid tumor malignancy with loss of SMARCA4 due to truncating mutation and/or deletion by local testing that have either progress on or ineligible for standard of care therapy
• Must have measurable or non-measureable (but evaluable) disease
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Willing to provide either archival or fresh tumor tissue sample
• Adequate organ function (hematology, renal, and hepatic)

Exclusion Criteria:

• Participants with solid tumors with known concomitant SMARCA2 mutation or loss of protein expression
• Clinically significant or uncontrolled cardiac disease, uncontrolled electrolyte disorders, uncontrolled or symptomatic central nervous system (CNS) metastases or leptomeningeal disease
• History of another malignancy within 3 years except for adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancies, or malignancies previously treated with curative intent and not on active therapy or expected to require treatment or recurrence during the study
• Concurrent treatment with strong or moderate CYP3A4 inhibitor or inducer