Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as PTC596
Unesbulin · 3 trials · 3 indications
To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of Unesbulin in combination with and following conventional chemotherapy and as maintenance as a capsule (weight-based dosing) and a tablet (fixed dosing). Standard chemotherapy will be comprised of carboplatin and weekly paclitaxel. The DLTs will be based on adverse events that occur during administration of the first 2 cycles of combination Unesbulin and chemotherapy (a cycle = 21 days).
To examine the tolerability of the combination at the MTD of Unesbulinassessed in combination with standard neoadjuvant chemotherapy.
To determine the recommended phase II dose (RP2D) of Unesbulin in combination with standard neoadjuvant chemotherapy.
MTD will be determined using the TITE-CRM for dose-finding. MTD is defined as the dose associated with a target probability of DLT of 0.25.
Determine the RP2D based on occurrence of DLTs and/or biological efficacy as determined by biomarker changes.
| Arm | Type | Description |
|---|---|---|
| Carboplatin/Paclitaxel + PTC596 | EXPERIMENTAL | Carboplatin AUC 6mg/L IV on day 1; Paclitaxel 175mg/m2 IV on day 1; Unesbulin PO, twice a week, on day 1, 4, 8, 11, 15 and 18 per 21-day cycle for the first 3 cycles. |
| Unesbulin and Dacarbazine | EXPERIMENTAL | Participants will receive unesbulin orally twice weekly in combination with dacarbazine IV once every 21 days. The first participant will receive dacarbazine 1000 mg/m\^2 IV every 21 days in combination with unesbulin 200 mg tablet orally twice weekly. For subsequent participants, the dose level at which treatment is initiated will be selected based on the TITE-CRM using the most up to date dose DLT information from all participants previously treated. Participants will receive unesbulin 300 mg twice weekly in combination with dacarbazine in the expansion cohort. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason. |
| Cohort 1 | EXPERIMENTAL | PTC 596 administered twice daily- Dose level 0.65mg/kg |
| Cohort 2 | EXPERIMENTAL | PTC 596 administered twice daily-Dose level 1.3mg/kg |
| Cohort 3 | EXPERIMENTAL | PTC 596 administered twice daily-2.6mg/kg |
| Cohort 4 | EXPERIMENTAL | PTC 596 administered twice daily-Dose level 5.2mg/kg |
| Cohort 5 | EXPERIMENTAL | PTC 596 administered twice daily-Dose level 10mg/kg |
| Cohort 6 | EXPERIMENTAL | PTC 596 administered twice daily-Dose level 7mg/kg |
| Cohort 7 (Bio Marker cohort) | EXPERIMENTAL | PTC 596 administered twice daily-Dose level 5.2mg/kg |
| Name | Type | Description |
|---|---|---|
| Unesbulin | DRUG | Unesbulin will be given in combination with carboplatin and paclitaxel for up to 7 cycles depending on which cohort the patient is in. |
| Dacarbazine | DRUG | Dacarbazine will be administered as per the dose and schedule specified in the arm. |
| PTC596 | DRUG | PTC 596 will be administered orally twice a day until unmanageable toxicity, disease progression, or withdrawal of consent is noted |
Inclusion Criteria: * Histologically documented epithelial ovarian, primary peritoneal or fallopian tube carcinoma or high grade serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma,or adenocarcinoma not otherwise spec...
Unesbulin is an investigational small molecule being studied in oncology for ovarian cancer and leiomyosarcoma. It has been evaluated in Phase 1 clinical trials, including a study in women with ovarian cancer receiving neoadjuvant chemotherapy and a study in combination with dacarbazine in participants with advanced leiomyosarcoma.
Unesbulin is being developed by PTC Therapeutics, Inc., a biopharmaceutical company traded on NASDAQ under the ticker symbol PTCT. The company has sponsored Phase 1 clinical trials of the drug in ovarian cancer and leiomyosarcoma.
Unesbulin is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Two Phase 1 trials have been completed, one in ovarian cancer and one in leiomyosarcoma, but the drug remains in early-stage clinical testing.
Unesbulin has been studied in two completed Phase 1 trials. NCT03206645 evaluated unesbulin in women with ovarian cancer receiving neoadjuvant chemotherapy, enrolling 27 participants. NCT03761095 studied unesbulin in combination with dacarbazine in participants with advanced leiomyosarcoma, enrolling 41 participants.
Yes, Unesbulin is also known as PTC596. The clinical trial NCT03761095, which studied unesbulin in combination with dacarbazine in advanced leiomyosarcoma, refers to the drug as unesbulin (PTC596).