NCT06682806

A Study of PRT3789 in Combination With Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation

Terminated Phase 2 Last updated 2 February 2026

What this trial tests

Phase 2 trial testing PRT3789 in Advanced Solid Tumor in 6 participants. Terminated before completion.

Timeline

3 June 2025

Primary endpoint
23 January 2026

23 January 2026

Quick facts

Lead sponsor	Prelude Therapeutics
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	6
Start date	3 June 2025
Primary completion	23 January 2026
Estimated completion	23 January 2026
Sites	9 locations across United States, Spain

Drugs / interventions tested

• PRT3789 — full drug profile →
• pembrolizumab (pembrolizumab) — full drug profile →

Conditions studied

• Advanced Solid Tumor — all drugs for Advanced Solid Tumor →
• Esophageal Cancer — all drugs for Esophageal Cancer →
• Metastatic Solid Tumor — all drugs for Metastatic Solid Tumor →
• Non-small Cell Lung Cancers — all drugs for Non-small Cell Lung Cancers →

Sponsor

Prelude Therapeutics — full company profile →

Who can join

18 and older, any sex, with Advanced Solid Tumor or Esophageal Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This is a Phase 2 an open-label, multi-center study to determine the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and anti-tumor activity of PRT3789 in combination with pembrolizumab in patients with advanced, recurrent or metastatic solid tumors with a SMARCA4 mutation.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. NDA Submission of Vepdegestrant (ARV-471) to U.S. FDA: The Beginning of a New Era of PROTAC Degraders.
   Ma Z, Zhou J. · · 2025 · cited 28× · PMID 40702893 · DOI 10.1021/acs.jmedchem.5c01818
2. Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies.
   Yang J, Zhou F, Luo X, Fang Y, et al · · 2025 · cited 10× · PMID 40032852 · DOI 10.1038/s41420-025-02366-3
3. Genetic drivers of tumor microenvironment and immunotherapy resistance in non-small cell lung cancer: the role of <i>KEAP1</i>, <i>SMARCA4</i>, and <i>PTEN</i> mutations.
   Paredes R, Borea R, Drago F, Russo A, et al · · 2025 · cited 8× · PMID 40764107 · DOI 10.1136/jitc-2025-012288
4. Proteolysis-Targeting Chimera (PROTAC): Current Applications and Future Directions.
   Fan G, Chen S, Zhang Q, Yu N, et al · · 2025 · cited 6× · PMID 41049269 · DOI 10.1002/mco2.70401
5. Thoracic SMARCA4-deficient undifferentiated tumor: diagnostic characteristics, molecular insights, and treatment approaches.
   Song J, Gersten A, Herzberg B, Halmos B. · · 2025 · cited 2× · PMID 40421964 · DOI 10.1093/oncolo/oyaf121
6. Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.
   Li J, Zhang L, Shang Y, Liu J, et al · · 2026 · cited 1× · PMID 41537447 · DOI 10.1002/ctm2.70586
7. Prognostic Implications of SMARCA4, ARID1A, and Other BAF Mutations in Non-Small Cell Lung Cancer.
   Khalil A, Collins MP, Quintás-Cardama A. · · 2025 · cited 1× · PMID 41387924 · DOI 10.1002/cam4.71442
8. Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.
   Knoll N, Neamati N, Üren A. · · 2026 · PMID 41988372 · DOI 10.1021/acsptsci.5c00730