Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT04585750 | The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE) | PHASE1 | RECRUITING | 300 | — | — | Oct 29, 2020 | Dec 31, 2027 | Mar 12, 2026 | 76 | United States, Australia +7 |
Number of participants with treatment related adverse events
RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data
Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt
Number of participants with treatment related adverse events
Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt
RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data
Number of participants with treatment related adverse events
Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review across all cohorts
Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review in the ovarian cancer cohort
| Arm | Type | Description |
|---|---|---|
| Phase 1 Monotherapy Dose Escalation | EXPERIMENTAL | Multiple dose levels of daily oral rezatapopt will be evaluated in an escalating manner, to determine the maximum tolerated dose and to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of rezatapopt to recommend a Phase 2 dose (RP2D). |
| Phase 1b Combination Therapy Dose Escalation, Part 1 | EXPERIMENTAL | Multiple dose levels of daily oral rezatapopt in combination with a stable dose of pembrolizumab (200 mg IV q3 weeks) will be evaluated in an escalating manner, to determine the maximum tolerated dose and to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of PC14586 to recommend a Phase 2 dose (RP2D) of rezatapopt when administered in combination with pembrolizumab. |
| Phase 1b Combination Therapy Dose Expansion, PD(L)-1 naive patients | EXPERIMENTAL | Additional (expansion of) participants will enroll at the RP2D of daily oral PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab (200 mg IV q3 weeks) for continued evaluation. Participants will have advanced solid tumors harboring a p53 Y220C mutation and are PD(L)-1 naive patients. |
| Phase 1b Combination Therapy Dose Expansion, PD(L)-1 relapsed/refractory patients | EXPERIMENTAL | Additional (expansion of) participants will enroll at the RP2D of daily oral rezatapopt when administered in combination with pembrolizumab (200 mg IV q3 weeks) for continued evaluation. Participants will have advanced solid tumors harboring a p53 Y220C mutation and are PD(L)-1 relapsed/refractory patients. |
| Phase 2 Monotherapy Dose Expansion, Ovarian Cancer Cohort | EXPERIMENTAL | Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Ovarian Cancer Cohort participants will have locally advanced or metastatic ovarian cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
| Phase 2 Monotherapy Dose Expansion, Lung Cancer Cohort | EXPERIMENTAL | Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Lung Cancer Cohort participants will have locally advanced or metastatic lung cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
| Phase 2 Monotherapy Dose Expansion, Breast Cancer Cohort | EXPERIMENTAL | Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Breast Cancer Cohort participants will have locally advanced or metastatic breast cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
| Phase 2 Monotherapy Dose Expansion, Endometrial Cancer Cohort | EXPERIMENTAL | Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Endometrial Cancer Cohort participants will have locally advanced or metastatic endometrial cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
| Phase 2 Monotherapy Dose Expansion, Other Solid Tumors Cohort | EXPERIMENTAL | Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Other Solid Tumors Cohort participants will have locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
| Name | Type | Description |
|---|---|---|
| rezatapopt | DRUG | First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation. |
| pembrolizumab | DRUG | Participants receive pembrolizumab 200 mg by intravenous (IV) infusion over 30 minutes. |
Inclusion Criteria: * At least 18 years of age or 12 to 17 years of age after Safety Review Committee approval. * Locally advanced or metastatic solid malignancy with a TP53 Y220C mutation * Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 * Previously treated with one or more lines of an...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 2 | PHASE2 | pembrolizumab, V503, GARDASIL |
| Incyte Corporation | INCY | 1 | PHASE2 | Chemotherapy, Retifanlimab |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE1 | KFA115, pembrolizumab |
| Iovance Biotherapeutics Inc | IOVA | 2 | PHASE2 | E7 TCR-T cells, Aldesleukin |
| AstraZeneca PLC | AZN | 1 | — | Trastuzumab deruxtecan |