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Also known as TAK-676
Dazostinag · 3 trials · 5 indications
AE: any untoward medical occurrence in participants administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. TEAE: any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug is considered treatment emergent. Severity grade is defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Grade 1: Mild (asymptomatic/mild symptoms; clinical/diagnostic observations only; intervention not indicated); Grade 2: Moderate (minimal, local/noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living \[ADL\]); Grade 3: Severe (severe/medically significant but not immediately life-threatening hospitalization/prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4: Life-threatening consequences, urgent intervention indicated; Grade 5: Death related to AE.
A DLT was defined as any TEAE that occurred during Cycle 1 and was considered by investigator to be at least possibly related to TAK-676 in combination with pembrolizumab. TEAEs meeting DLT definitions occurring in later cycles were considered in the determination of recommended phase 2 dose (RP2D) of TAK-676. DLTs were assessed based on NCI CTCAE version 5.0.
TEAE: any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug is considered treatment emergent. An SAE is defined as any untoward medical occurrence that: 1) results in death, 2) is life-threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) leads to a congenital anomaly/birth defect in the offspring of the participant or 6) is a medically important event that satisfies any of the following: a) may require intervention to prevent items 1 through 5 above. b) may expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization
TEAE: Any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug is considered treatment emergent.
TEAE: Any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug is considered treatment emergent.
Quantification of biomarker-positive and biomarker-negative cells will be performed within the tumor microenvironment around each of the injection sites in each resected patient sample by IHC and ISH. An aggregate analysis of this quantification may be done across patient samples in each substudy to evaluate trends in tumor response. The biomarkers evaluated may include, but are not limited to, biomarkers for cell death (e.g., cleaved caspase 3), T-cells (e.g., Cluster of Differentiation 3 (CD3), Cluster of Differentiation 8/Granzyme B, Cluster of Differentiation), natural killer (NK)/myeloid cells (e.g., Cluster of Differentiation 56/Granzyme B, Cluster of Differentiation 86, Cluster of Differentiation 68, Cluster of Differentiation 163), and proinflammatory cytokines (e.g., interferon gamma, tumor necrosis factor alpha, interferon gamma-induced protein 10).
| Arm | Type | Description |
|---|---|---|
| Combination Dose Escalation Phase: Radiation + Pembrolizumab + TAK-676 | EXPERIMENTAL | Participants will receive image-guided radiation therapy between Day -8 and Day -2. Participants will then receive pembrolizumab 200 milligram (mg), infusion, intravenously (IV), once on Day 1 of Cycle 1 and then every 3 weeks in each 21-day treatment cycle, followed by TAK-676 infusion with escalating doses (0.2 mg and above), IV, once on Days 1, 8, 15 in each 21-day treatment cycle until disease progression, intolerance to pembrolizumab or TAK-676 or withdrawal of consent, whichever occurs first. |
| 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. |
| TAK-676, Carboplatin, 5-FU, & Paclitaxel | EXPERIMENTAL | Patients who are scheduled for surgical biopsy or tumor resection surgery will be injected at least four hours to up to four days prior to surgery using the CIVO device. Each needle of the CIVO device will deliver up to 8.3 microliters of solution, including a vehicle control (sterile saline) or subtherapeutic microdoses of TAK-676, carboplatin, 5-fluorouracil (5- FU), or paclitaxel as single agents or in combination. Each microdose is simultaneously injected in a columnar fashion through each of 8, 5, or 3 needles (in a device configuration determined by tumor dimensions) into a single solid tumor or effaced metastatic lymph node. |
| Name | Type | Description |
|---|---|---|
| Pembrolizumab | DRUG | IV infusion. |
| TAK-676 | DRUG | IV infusion. |
| Image-guided radiation therapy | RADIATION | Radiation therapy. |
| Dazostinag | DRUG | Dazostinag intravenous infusion. |
| Platinum | DRUG | Carboplatin or Cisplatin intravenous infusion |
| 5-fluorouracil | DRUG | 5-fluorouracil intravenous infusion |
| Carboplatin | DRUG | Intratumoral microdose injection by the CIVO device. |
| 5-FU | DRUG | Intratumoral microdose injection by the CIVO device. |
| Paclitaxel | DRUG | Intratumoral microdose injection by the CIVO device. |
| TAK-676 + Carboplatin | COMBINATION_PRODUCT | Intratumoral microdose injection by the CIVO device. |
| Carboplatin + Paclitaxel | COMBINATION_PRODUCT | Intratumoral microdose injection by the CIVO device. |
| Carboplatin + 5-FU | COMBINATION_PRODUCT | Intratumoral microdose injection by the CIVO device. |
| TAK-676 + Carboplatin + 5-FU | COMBINATION_PRODUCT | Intratumoral microdose injection by the CIVO device. |
| TAK-676 + Carboplatin + Paclitaxel | COMBINATION_PRODUCT | Intratumoral microdose injection by the CIVO device. |
Inclusion Criteria: 1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 2. Participants must have at least 2 measurable lesions (i.e. ≥10 mm longest diameter for extranodal lesions, ≥15 mm short axis for lymph nodes), with at least one inside and at least one other outside of...
Dazostinag is an investigational small molecule developed by Takeda Pharmaceutical Company Limited for the treatment of advanced or metastatic solid neoplasms. It is a Phase 1 oncology candidate that has been studied both as a single agent and in combination with pembrolizumab in adults with solid tumors.
Dazostinag is being studied for use in adults with advanced or metastatic solid neoplasms, a broad group of solid tumor cancers. It has been evaluated as a single agent and in combination with pembrolizumab. It is investigational and has not been approved for any indication.
Dazostinag is developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. Takeda is the sponsor of the clinical program evaluating dazostinag in advanced or metastatic solid tumors.
Dazostinag is in Phase 1 clinical development. Its single registered trial, NCT04420884, was a Phase 1 study that has been completed. Dazostinag is investigational and has not been approved by the FDA for any indication.
Dazostinag has been studied in one clinical trial, NCT04420884, titled A Study of Dazostinag as Single Agent and Dazostinag in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors. The Phase 1 trial enrolled 248 participants across the United States, Europe, Canada, China, Israel, Japan, and Puerto Rico, and it is completed.
Yes, the dazostinag Phase 1 trial NCT04420884 was biomarker selected, meaning enrollment was guided by a biomarker. The study evaluated dazostinag as a single agent and in combination with pembrolizumab in adults with advanced or metastatic solid tumors and enrolled 248 participants.