A Study of TAK-981 Given With Pembrolizumab in Participants With Select Advanced or Metastatic Solid Tumors
Summary
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) |
3; 6; 33; 19 | — |
| PRIMARY Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) |
0; 0; 2; 1 | — |
| PRIMARY Phase 1: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs) |
0; 2; 20; 15 | — |
| PRIMARY Phase 1: Number of Participants With One or More Serious Adverse Events (SAEs) |
0; 3; 17; 10 | — |
| PRIMARY Phase 1: Number of Participants With One or More TEAEs Leading to Dose Modifications and Treatment Discontinuation |
0; 3; 22; 11; 0; 3 | — |
| PRIMARY Phase 1: Number of Participants With Clinically Significant Laboratory Values |
1; 3; 7; 6; 1; 1 | — |
| PRIMARY Phase 2: Overall Response Rate (ORR) as Assessed by the Investigator According to RECIST, Version 1.1 |
20; 0; 30; 0; 25; 7.7 | — |
| SECONDARY Phase 1: Cmax: Maximum Observed Plasma Concentration for TAK-981 |
335; 728; 888; 1290; 280; 448 | — |
| SECONDARY Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981 |
1.22; 1.27; 1.17; 1.20; 1.18; 1.41 | — |
| SECONDARY Phase 1: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 |
880; 1370; 1950; 2580; 814; 976 | — |
| SECONDARY Phase 1: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 |
909; 1400; 2020; 2660; 845; 1010 | — |
| SECONDARY Phase 1: t1/2z: Terminal Disposition Phase Half-life for TAK-981 |
5.88; 5.58; 5.72; 6.79; 5.83; 5.68 | — |
| SECONDARY Phase 1: CL: Total Clearance After Intravenous Administration for TAK-981 |
51.1; 47.2; 51.3; 51.0; 51.7; 62.5 | — |
| SECONDARY Phase 1: Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 |
312; 181; 240; 240; 323; 314 | — |
| SECONDARY Phases 1 and 2: Disease Control Rate (DCR) |
33.3; 50.0; 30.3; 44.4; 80.0; 62.5 | — |
| SECONDARY Phases 1 and 2: Durable Response Rate (DRR) |
0; 16.7; 6.1; 0; 10.0; 0 | — |
| SECONDARY Phases 1 and 2: Duration of Response (DOR) |
17.12; 7.39; 3.71; 7.62; NA; NA | — |
| SECONDARY Phases 1 and 2: Progression-free Survival (PFS) |
2.00; 4.21; 1.99; 2.11; 3.71; 4.59 | — |
| SECONDARY Phases 1 and 2: Time to Response (TTR) |
4.17; NA; NA; 4.01; 6.01; NA | — |
| SECONDARY Phases 1 and 2: Time to Progression (TTP) |
2.00; 4.21; 2.07; 2.07; 3.71; 4.01 | — |
| SECONDARY Phase 2: Overall Survival (OS) |
NA; 10.12; 14.55; NA; NA; NA | — |
| SECONDARY Fold Change From Baseline in TAK-981-/Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Peripheral Blood Lymphocytes |
8.1; 7.0; 8.5; 8.4; 5.1; 5.0 | — |
| SECONDARY Fold Change From Baseline in SUMO 2/3 Inhibition in Peripheral Blood Lymphocytes |
0.7; 0.6; 0.6; 0.5; 0.8; 0.6 | — |
| SECONDARY Phase 2: Percentage of Participants With One or More Treatment Emergent Adverse Events (TEAEs) |
100; 100; 100; 100; 100; 93.3 | — |
| SECONDARY Phase 2: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs) |
7; 5; 18; 8; 14; 4 | — |
| SECONDARY Phase 2: Number of Participants With One or More TEAEs Leading to Dose Modifications and Treatment Discontinuation |
11; 6; 15; 5; 15; 6 | — |
Eligibility Criteria
Inclusion Criteria
- 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 treatment unless such treatments were completed less than 12 months prior to the current tumor recurrence.
A. Non-squamous NSCLC for which prior standard first-line treatment containing an anti-programmed cell death protein 1/programmed cell death protein 1 ligand (PD-1/PD-L1) checkpoint inhibitor (CPI) alone or in combination has failed and that has progressed on no more than 1 prior systemic therapy. In Phase 2, participants with nonsquamous NSCLC must have not received more than 1 prior systemic therapy and must not have presented with disease progression during the first 6 months of treatment with first-line CPI/anti-PD-(1/L1)-containing therapy.
Note: In Phase 1, participants with nonsquamous NSCLC and known driver mutations/genomic aberrations (e.g., epidermal growth factor receptor (EGFR), B-Raf proto-oncogene mutation V600E [BRAF V600E], and ROS proto-oncogene 1 [ROS1] sensitizing mutations, neurotrophic receptor tyrosine kinase [NRTK] gene fusions, and anaplastic lymphoma kinase [ALK] rearrangements) must have also shown progressive disease after treatment with a commercially available targeted therapy. In Phase 2, participants with driver mutations are not eligible.
B. CPI-naive cervical cancer (squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix) participants for whom prior standard first-line treatment has failed and who have received no more than 1 prior systemic line of therapy for recurrent or Stage IVB cervical cancer. Note: The following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric-type adenocarcinoma, clear-cell carcinoma, and mesonephric carcinoma. Histologic confirmation of the original primary tumor is required via pathology report. Note: First-line treatment must have consisted of platinum-containing doublet. Chemotherapy administered concurrently with primary radiation (e.g., weekly cisplatin) is not counted as a systemic chemotherapy regimen.
C. CPI-naïve microsatellite stable-colorectal cancer (MSS-CRC) participants for whom prior standard first-line treatment has failed and who have progressed on no more than 3 chemotherapy regimens.
Note: Participants must have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimens if indicated.
D. Unresectable Stage III or Stage IV cutaneous melanoma that has not received prior therapy in the metastatic setting.
Note: Participants with acral melanoma are not eligible. Participants who have presented with disease relapse after ≥6 months of the last dose of CPI or BRAF-mitogen-activated protein kinase kinase (MEK) inhibitor in the adjuvant setting are eligible.
E. Squamous NSCLC for which prior standard first-line treatment containing an anti-PD-(1/L1) checkpoint inhibitor alone or in combination has failed. Participant must have not received more than 1 prior systemic therapy and must not have presented with disease progression during the first 6 months of treatment with first-line CPI/anti-PD-(1/L1)-containing therapy.
F. Squamous or nonsquamous NSCLC for which prior standard first-line treatment containing an anti-PD-(1/L1) checkpoint inhibitor alone or in combination has failed within 6 months from the initiation of the CPI. Participants must not have received more than 1 prior systemic therapy in the metastatic setting.
Note: Participants with driver mutations are not eligible.
- Has at least 1 radiologically measurable lesion based on RECIST, Version 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Has a performance status of 0 or 1 on the Eastern Cooperative Group Onco
Data sourced from ClinicalTrials.gov (NCT04381650). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.