Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| KEYNOTE-G02 | Other Identifier | Merck Sharp and Dohme LLC | |
| MK-3475-G02 | Other Identifier | Merck Sharp and Dohme LLC | |
| 2024-516889-11-00 | EU Trial (CTIS) Number |
Not provided
Not provided
Not provided
Sponsor decision
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
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.
This is an open-label, multi-center Phase 2 study of PRT 3789, a first-in-class SMARCA2 targeted protein degrader, in combination with pembrolizumab, a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor, evaluating patients with Advanced or Metastatic Solid Tumors with a SMARCA4 Mutation. This study consists of 2 parts. Part 1 is a safety run-in and will establish the dose of PRT3789 to be used in combination with pembrolizumab in the main study (Part 2). For Part 2 (Main study) primary endpoints are ORR (defined as the proportion of patients with a confirmed best overall response of either complete response or partial response) and duration of response per investigator assessment per RECIST v1.1.
Approximately 46 to 60 patients will be enrolled in Part 1 and Part 2 based on the dose of PRT3789 selected/cleared during the safety run-in.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PRT3789/Pembrolizumab combination | Experimental | PRT3789 is administered as an intravenous infusion once weekly for 3 weeks; Pembrolizumab is administered at 200 mg as an intravenous infusion over 30 min every 3 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PRT3789 | Drug | PRT3789 is administered as an intravenous infusion once weekly for 3 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability of PRT3789 in combination with pembrolizumab as measured by incidence of DLTs (Part 1) | Safety and tolerability will be evaluated by incidence of dose-limiting toxicities (DLTs) | Baseline through completion of study, an average of 2 years |
| Safety and tolerability of PRT3789 in combination with pembrolizumab as measured by incidence and severity of AEs according to NCI CTCAE (Part 1) | Safety and tolerability will be evaluated by incidence and severity of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | Baseline through study completion, an average of 2 years |
| Efficacy of PRT3789 in combination with pembrolizumab in patients with advanced or metastatic esophageal or NSCLC and deleterious SMARCA4 mutation: Objective Response Rate (Part 2) | Objective response rate defined as the proportion of patients with a confirmed best overall response of either complete response or partial response, as determined per investigator assessment by RECIST v1.1 | Baseline through study completion, an average of 2 years |
| Efficacy of PRT3789 in combination with pembrolizumab in patients with advanced or metastatic esophageal or NSCLC and deleterious SMARCA4 mutation: Duration of Response (Part 2) | Duration of response defined as the time from the date of the first documented response (complete response or partial response) to the earliest date of disease progression, as determined per investigator assessment by RECIST v1.1, or death due to any cause | Baseline through study completion, an average of 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of PRT3789 in combination with pembrolizumab: Objective Response Rate (Part 1) | Objective response rate defined as the proportion of patients with a confirmed best overall response of either complete response or partial response, as determined per investigator assessment by RECIST v1.1 | Baseline through study completion, an average of 2 years |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Florida Cancer Specialists | West Palm Beach | Florida | 33401 | United States | ||
| Karmanos Cancer Institute |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| pembrolizumab | Drug | Pembrolizumab is administered at 200 mg as an intravenous infusion over 30 min every 3 weeks |
|
|
| Efficacy of PRT3789 in combination with pembrolizumab: Duration of Response (Part 1) | Duration of response defined as the time from the date of the first documented response (complete response or partial response) to the earliest date of disease progression, as determined per investigator assessment by RECIST v1.1, or death due to any cause | Baseline through study completion, an average of 2 years |
| Efficacy of PRT3789 in combination with pembrolizumab (part 1 and part 2): Clinical Benefit Response | Clinical benefit response defined as the proportion of patients with a best overall response of complete response, partial response, or durable stable disease (24 weeks or longer), as determined per investigator assessment by RECIST v1.1 | Baseline through study completion, an average of 2 years |
| Efficacy of PRT3789 in combination with pembrolizumab (part 1 and part 2): Progression-Free Survival | PFS defined as the time from the date of first dose of investigational product to the date of first documented progressive disease, as determined per investigator assessment by RECIST v1.1, or death due to any cause | Baseline through study completion, an average of 2 years |
| Efficacy of PRT3789 in combination with pembrolizumab (part 1 and part 2): Overall Survival | Overall survival defined as the time from the date of first dose of investigational product to death due to any cause | Baseline through study completion, an average of 2 years |
| Safety and tolerability of PRT3789 in combination with pembrolizumab as measured by AEs according to NCI CTCAE | Safety and tolerability will be evaluated by incidence and severity of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | Baseline through study completion, an average of 2 years |
| Safety and tolerability of PRT3789 in combination with pembrolizumab: as measured by key clinical laboratory parameters | Laboratory shift tables reflecting mean and CTCAE grade changes from baseline values for key laboratory analytes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, hemoglobin, platelet count, neutrophil count, lymphocyte count, and leukocyte count | Baseline through study completion, an average of 2 years |
| Safety and tolerability as measured by incidence of dose modification due to AEs | Safety and tolerability will be evaluated by dose interruption, modification, and discontinuation due to adverse events (AEs) | Baseline through study completion, an average of 2 years |
| PK profile of PRT3789 in combination with pembrolizumab: Maximum observed plasma concentration: Maximum observed plasma concentration | Pharmacokinetics will be calculated including the maximum observed plasma concentration | Baseline through study completion, an average of 2 years |
| PK profile of PRT3789 in combination with pembrolizumab: Area under the curve | Pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC) | Baseline through study completion, an average of 2 years |
| PK profile of PRT3789 in combination with pembrolizumab: Time of maximum concentration (Tmax) and half-life (T1/2) | Pharmacokinetic parameters will be calculated using standard non-compartmental techniques | Baseline through study completion, an average of 2 years |
| Detroit |
| Michigan |
| 48201 |
| United States |
| John Theurer Cancer Center at Hackensack University Medical Center | Hackensack | New Jersey | 07601 | United States |
| SCRI Oncology Partners | Nashville | Tennessee | 37203 | United States |
| Tennessee Oncology, PLLC - Greco-Hainsworth Centers for Research | Nashville | Tennessee | 37203 | United States |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| IOB - Next Oncology - Hospital Quironsalud Barcelona | Barcelona | 08023 | Spain |
| START Barcelona - HM Nou Delfos | Barcelona | 08023 | Spain |
| Hospital Universitario Fundacion Jimenez Diaz - Servicio de Oncologia | Madrid | 28040 | Spain |
| ID | Term |
|---|---|
| D004938 | Esophageal Neoplasms |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C582435 | pembrolizumab |
Not provided
Not provided
Not provided