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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT04420884 | A Study of Dazostinag as Single Agent and Dazostinag in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors | PHASE1 | COMPLETED | 248 | — | — | Jul 22, 2020 | Mar 30, 2026 | Apr 8, 2026 | 62 | United States, Austria +9 |
A severity grade is defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Grade 1 scales as Mild (asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 scales as Moderate (minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living \[ADL\]); Grade 3 scales as Severe (severe or medically significant but not immediately life threatening hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 scales as Life-threatening consequences, urgent intervention indicated, and Grade 5 scales as Death related to Adverse Event (AE).
A DLT will be defined as any of the TEAEs, but not limited to, those that occur during Cycle 1 and are considered by the investigator to be at least possibly related to dazostinag as a SA or in combination with pembrolizumab. TEAEs meeting DLT definitions occurring in Cycle 2 or later will be considered in the determination of the RDE of dazostinag, both in the dazostinag SA and the combination with pembrolizumab arms. Toxicity will be evaluated according to NCI CTCAE version 5.0.
| Arm | Type | Description |
|---|---|---|
| Part 1 (Monotherapy Dose Escalation Phase): Dazostinag Safety Lead-in + Dazostinag SA [Part 1A] | EXPERIMENTAL | Safety Lead-in: Dazostinag 0.1 mg, infusion, intravenously (IV), once weekly, on Days 1, 8 and 15 in 21-day treatment cycles. Dazostinag SA Dose Escalation (Part 1A): Dazostinag single agent (SA), infusion, IV, once weekly on Days 1, 8 and 15 in each 21-day treatment cycles with escalating doses (0.2 mg and above). The dosing will be initiated in the Dazostinag SA Dose Escalation Phase based on the available safety and tolerability data from the Safety Lead-in. |
| Part 1B (Combination Dose Escalation Phase): Dazostinag + Pembrolizumab | EXPERIMENTAL | Dazostinag escalating doses (0.2 mg and above) in combination with pembrolizumab 200 mg, infusion, IV, once weekly on Days 1, 8 and 15 in each 21-day treatment cycle. Pembrolizumab 200 mg will be administered 1 hour prior to Dazostinag once every 3 weeks (Q3W). The dosing will be initiated when at least two dose levels (DLs) of Part 1A have been evaluated. |
| Arm A: Japan Safety Lead-in Dazostinag + Pembrolizumab | EXPERIMENTAL | Dazostinag 5.0 mg, infusion, IV, in Japanese participants with advanced or metastatic solid tumors on Days 1, 8, and 15 in each 21-day cycle in combination with pembrolizumab 200 mg administered Q3W, IV, on Day 1 in each 21-day cycle. Additional dose levels of Dazostinag (such as 14.0 mg) in combination with pembrolizumab (200 mg, Q3W) may be explored in the Safety Lead-in. |
| Arm B: Japan Safety Lead-in Dazostinag Transitioned to Pembrolizumab | EXPERIMENTAL | Dazostinag 5.0 mg, infusion, IV, as an SA once on Day 1 in Cycle 0 (cycle length=7 days) in Japanese participants with advanced or metastatic solid tumors based on confirmation of tolerability in Arm A. Following Cycle 0 (7 days), participants will be transitioned to the same dose level of dazostinag on Days 1, 8, and 15 of each 21-day cycle in combination with pembrolizumab administered Q3W, IV, on Day 1 in each 21-day cycle. Additional dose levels of dazostinag (such as ≥ 7.0 mg) in combination with pembrolizumab (200 mg, Q3W) may be explored in the Safety Lead-in. |
| Part 2A (SCCHN CPS ≥ 1 Dose Expansion and Optimization Phase): Dazostinag + Pembrolizumab | EXPERIMENTAL | Dazostinag 5.0 mg, infusion, IV, will be administered in participants with squamous cell carcinoma of head and neck (SCCHN) at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W. Dose optimization may be performed in this phase. |
| Part 2B (SCCHN Dose Expansion Phase): Dazostinag + Pembrolizumab + Chemotherapy | EXPERIMENTAL | Dazostinag 5.0 mg, infusion, IV, will be administered in participants with SCCHN at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle. Pembrolizumab infusion, IV will be administered at 200 mg Q3W. Platinum-based chemotherapy comprising the combination of carboplatin (target area under the curve of 5 milligrams per milli Liters per minute (mg/mL/minute) \[AUC 5\]) or cisplatin (100 milligrams per square meter \[mg/m\^2\] Day 1 of each treatment cycle), and 5-fluorouracil (\[5-FU\]; 1000 mg/m\^2 per day for 4 consecutive days) Q3W for up to 6 cycles. |
| Part 3A (Expansion Phase in CRC): Dazostinag + Pembrolizumab in MSI-H/dMMR CRC | EXPERIMENTAL | Dazostinag 5.0 mg, infusion, IV, will be administered in participants with microsatellite instability-high /mismatch repair deficient (MSI-H/dMMR) colorectal cancer (CRC) at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W. |
| Part 3B (Expansion Phase in CRC): Dazostinag + Pembrolizumab in MSS/pMMR CRC | EXPERIMENTAL | Dazostinag 5.0 mg, infusion, IV, will be administered in participants with microsatellite stable/mismatch repair proficient (MSS/pMMR) CRC at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle. along with pembrolizumab 200 mg infusion, IV, Q3W. |
| Name | Type | Description |
|---|---|---|
| Dazostinag | DRUG | Dazostinag intravenous infusion. |
| Pembrolizumab | DRUG | Pembrolizumab intravenous infusion. |
| Platinum | DRUG | Carboplatin or Cisplatin intravenous infusion |
| 5-fluorouracil | DRUG | 5-fluorouracil intravenous infusion |
Inclusion Criteria: 1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 2. Dazostinag SA (dose escalation Part 1A): o With histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors that have no standard therapeutic options or are i...