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Also known as [14C] Subasumstat, Subasumstat
TAK-981 · 2 trials · 2 indications
An adverse event (AE) is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 except cytokine release syndrome (CRS), which was graded according to American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS.
DLTs were evaluated according to NCI CTCAE Version 5.0 except CRS, which was graded according to ASTCT Consensus Grading for CRS.
AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. A severity grade was evaluated as per the NCI CTCAE Version 5.0, except for CRS, which was assessed by ASTCT Consensus Grading for CRS.
An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent.
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy.
Laboratory parameters included clinical chemistry, hematology, and urinalysis. Participants with at least 1 Grade 3 or 4 Lab Abnormalities were reported.
ORR is defined as the percentage of participants who achieve Complete Response (CR) and Partial Response (PR) (determined by the investigator) during the study according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Quantification of biomarker-positive and biomarker-negative cells will be performed within the tumor microenvironment around each of the injection sites of each resected patient sample by IHC and ISH. An aggregate analysis of this quantification may be done across patient samples to evaluate trends in tumor response. List of biomarkers evaluated may include biomarkers for cell death (e.g. cleaved caspase 3), T-cells (e.g. CD3, CD8/Granzyme B), and natural killer (NK) or myeloid cells (e.g. CD56/Granzyme B, CD86, CD68).
| Arm | Type | Description |
|---|---|---|
| Dose Escalation: TAK-981 40 mg + Pembrolizumab | EXPERIMENTAL | Participants received TAK-981 40 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the recommended Phase 2 dose (RP2D) was determined (for a maximum of 24 months). |
| Dose Escalation: TAK-981 60 mg + Pembrolizumab | EXPERIMENTAL | Participants received TAK-981 60 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months). |
| Dose Escalation: TAK-981 90 mg + Pembrolizumab | EXPERIMENTAL | Participants received TAK-981 90 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months). |
| Dose Escalation: TAK-981 120 mg + Pembrolizumab | EXPERIMENTAL | Participants received TAK-981 120 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months). |
| Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg | EXPERIMENTAL | Participants with non-squamous non-small cell lung cancer (NSCLC) received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. |
| Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg | EXPERIMENTAL | Participants with NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. |
| Dose Expansion Phase: Cohort B: Cervical Cancer | EXPERIMENTAL | Participants with cervical cancer received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. |
| Dose Expansion Phase: Cohort C: MSS-CRC | EXPERIMENTAL | Participants with microsatellite stable colorectal cancer (MSS-CRC) received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. |
| Dose Expansion Phase: Cohort D: Cutaneous Melanoma | EXPERIMENTAL | Participants with cutaneous melanoma received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. |
| Dose Expansion Phase: Cohort E: Squamous NSCLC | EXPERIMENTAL | Participants with squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. |
| Dose Expansion Phase: Cohort F: CPI Refractory Squamous or Nonsquamous NSCLC | EXPERIMENTAL | Participants with checkpoint inhibitors (CPI) refractory squamous or non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. |
| CIVO Microdose Injection of TAK-981, Cetuximab, and Avelumab | EXPERIMENTAL | Patients who are scheduled for surgical biopsy or tumor resection surgery will be injected one day (Cohort 1) or three days (Cohort 2) 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-981, cetuximab, avelumab, TAK-981 combined with cetuximab, or TAK-981 combined with avelumab. 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. Approximately six patients will be assigned to each time point cohort. Cohort assignment is not sequential and will be selected by the Investigator based on clinic logistics and patient scheduling. Should one cohort fill in advance of the other, sites will be directed by Presage to enroll patients into the second cohort only. |
| Name | Type | Description |
|---|---|---|
| TAK-981 | DRUG | TAK-981 IV infusion. |
| Pembrolizumab | DRUG | Pembrolizumab IV infusion. |
| Cetuximab | BIOLOGICAL | Intratumoral microdose injection by the CIVO device. |
| Avelumab | BIOLOGICAL | Intratumoral microdose injection by the CIVO device. |
| TAK-981 + Cetuximab | COMBINATION_PRODUCT | Intratumoral microdose injection by the CIVO device. |
| TAK-981 + Avelumab | COMBINATION_PRODUCT | Intratumoral microdose injection by the CIVO device. |
Inclusion Criteria: 1. Has a histologically or cytologically documented, advanced (metastatic and/or unresectable) cancer as listed below that is incurable: Note: Prior neoadjuvant or adjuvant therapy included in initial treatment may not be considered first- or later-line standard of care treatmen...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 3 | PHASE2 | Pembrolizumab, Gardasil 9 |
| Incyte Corporation | INCY | 1 | PHASE2 | Retifanlimab |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE1 | KFA115 |
| Iovance Biotherapeutics Inc | IOVA | 2 | PHASE2 | Aldesleukin |
| AstraZeneca PLC | AZN | 1 | - | Trastuzumab deruxtecan |
TAK-981 is an investigational small molecule being studied in oncology for the treatment of advanced or metastatic solid tumors, including head and neck cancer. It is being developed by Takeda Pharmaceutical Company Limited and remains in clinical development rather than approved for commercial use.
TAK-981 has been evaluated in two completed Phase 1 studies. NCT04381650 tested TAK-981 with pembrolizumab in participants with select advanced or metastatic solid tumors across the United States, Brazil, China, Croatia, Japan, Latvia, Lithuania, Poland, and Switzerland. NCT04065555 was an early Phase 1 intratumoral microdosing study in head and neck cancer conducted in the United States.
TAK-981 is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. Takeda is the sponsor of the clinical program evaluating the compound in advanced or metastatic solid tumors and head and neck cancer.
TAK-981 is in Phase 1 clinical development. Its two completed studies include a Phase 1 trial of TAK-981 given with pembrolizumab in advanced or metastatic solid tumors and an early Phase 1 intratumoral microdosing study in head and neck cancer. It is investigational and has not been approved for any indication.
Across its two completed clinical studies, TAK-981 has enrolled a total of 173 participants. The Phase 1 trial of TAK-981 with pembrolizumab in advanced or metastatic solid tumors enrolled 161 participants, while the early Phase 1 intratumoral microdosing study in head and neck cancer enrolled 12 participants.
Yes, TAK-981 is a biomarker-selected therapy. Its clinical program has used biomarker-based patient selection, which means trial enrollment has been guided by specific molecular characteristics rather than an unselected patient population. This approach is common in early-phase oncology studies of targeted small molecules.