Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as MK-1454
Ulevostinag · 2 trials · 3 indications
ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by blinded independent central review (BICR), and the 95% confidence interval (CI) was based on the exact method for binomial data.
DLTs were assessed during the first cycle (21 days) \& are defined as: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia, Gr 4 thrombocytopenia, Gr 3 thrombocytopenia (if associated with clinically significant bleeding); nonhematologic adverse event (AE) ≥ Gr 3 (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention is required, leads to hospitalization, or persists for \>1 week); Gr 3 or 4 febrile neutropenia; drug-related toxicity that causes treatment discontinuation or dose delay \>7 days between consecutive doses during Cycle 1; drug-related toxicity that causes a \>2 week delay in Cycle 2 initiation; elevated aspartate aminotransferase or alanine aminotransferase lab value that is ≥3× upper limit of normal (ULN) \& an elevated total bilirubin value ≥2× ULN \& an alkaline phosphatase value \<2× ULN, in which no alternative reasons can be found; ≥Gr 2 immune-mediated uveitis; or Gr 5 toxicity.
AEs are defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study treatment, is also an AE.
AEs are defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study treatment, is also an AE.
| Arm | Type | Description |
|---|---|---|
| Ulevostinag+Pembrolizumab | EXPERIMENTAL | Participants receive ulevostinag 540 ug via intratumoral (IT) injection on Day 1 of every week for two 3-week cycles (Cycles 1-2), then on Day 1 of each 3-week cycle for up 33 cycles (Cycles 3-35), for a total of 35 cycles PLUS pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles. The total duration of treatment is up to approximately 2 years. |
| Pembrolizumab | ACTIVE_COMPARATOR | Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 cycles. The total duration of treatment is up to approximately 2 years. |
| Part 1 Arm 1: Ulevostinag (Cut/Subcut Lesions) | EXPERIMENTAL | Participants with cutaneous (cut) or subcutaneous (subcut) lesions will receive escalating doses of ulevostinag monotherapy via IT injection on Days 1, 8, and 15 of each 21-day cycle for Cycles 1, 2, and 3 and then on Day 1 of each 21-day cycle for Cycles 4 and beyond for up to 35 cycles (up to approximately 2 years). |
| Part 1 Arm 2: Ulevostinag +Pembro (Cut/Subcut Lesions) | EXPERIMENTAL | Participants with cut or subcut lesions will receive escalating doses of ulevostinag via IT injection on Days 1, 8, and 15 of each 21-day cycle for Cycles 1, 2, and 3 and then on Day 1 of each 21-day cycle for Cycles 4 and beyond PLUS pembrolizumab (pembro) via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years). |
| Part 1 Arm 3: Ulevostinag+Pembro (Visceral Lesions) | EXPERIMENTAL | Participants with visceral lesions will receive escalating dose frequencies of ulevostinag via IT injection at escalating dose frequencies (Day 1 of each 21-day cycle for up to 35 cycles, then Days 1 and 8 of each 21-day cycle for two cycles, then Day 1 of each 21 day cycle up to 35 cycles, then Days 1, 8, and 15 of each 21-day cycle for two cycles followed by Day 1 of each 21-day cycle up to 35 cycles, PLUS pembrolizumab IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (approximately 2 years). |
| Part 2 Cohort A: HNSCC Anti-PD-1/PD-L1 Refractory | EXPERIMENTAL | Participants with HNSCC who are anti-programmed cell death-1 or anti-programmed cell death-ligand 1 refractory will receive ulevostinag at the preliminary Recommended Phase 2 Dose (RP2D) determined by dose escalation in Part 1 Arm 1 and 2 via IT injection on Days 1, 8, and 15 of Cycles 1 and 2 and on Day 1 of each 21-day cycle from Cycle 3 onward (up to a total of 35 cycles) PLUS pembrolizumab via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years). |
| Part 2 Cohort B: Anti-PD-1/PD-L1 TrT-Naïve or Refractory TNBC | EXPERIMENTAL | Participants with TNBC who are anti-PD-1/PD-L1 treatment-naïve or who have refractory unresectable locally advanced or metastatic TNBC will receive ulevostinag at the preliminary RP2D determined by dose escalation in Part 1 via IT injection on Days 1, 8, and 15 of Cycles 1 and 2 and on Day 1 of each 21-day cycle from Cycle 3 onward (up to a total of 35 cycles) PLUS pembrolizumab via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years). |
| Part 2 Cohort C: Anti-PD-1/PD-L1 TrT-Naïve Solid Tumors-Liver | EXPERIMENTAL | Participants with solid tumors with liver metastases/lesions who are anti-PD-1/PD-L1 treatment-naïve will receive ulevostinag at the preliminary RP2D based on Part 1: ulevostinag + pembro (visceral lesions) treatment arm via IT injection in a to-be-determined dose and frequency, based on data from Arm 3, PLUS pembrolizumab via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years). |
| Name | Type | Description |
|---|---|---|
| Ulevostinag | DRUG | IT injection |
| Pembrolizumab | BIOLOGICAL | IV infusion |
Inclusion Criteria: * Has histologically or cytologically confirmed diagnosis of metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC) that is considered incurable by local therapies * Has not had prior systemic therapy administered in the recurrent or metastatic setti...
Ulevostinag is an investigational small molecule being studied for head and neck squamous cell carcinoma (HNSCC) and advanced solid tumors. It has been evaluated as a first-line treatment for metastatic or unresectable, recurrent HNSCC in combination with pembrolizumab, and as a monotherapy or combination therapy in advanced solid tumors or lymphomas.
Ulevostinag is being developed by Merck & Company, Inc. (ticker: MRK). The company has sponsored clinical trials of the drug in oncology, including a Phase 2 study in head and neck squamous cell carcinoma and a Phase 1 study in advanced solid tumors or lymphomas.
Ulevostinag is in Phase 2 clinical development. A Phase 2 trial (NCT04220866) has been completed in head and neck squamous cell carcinoma, and a Phase 1 trial (NCT03010176) has also been completed in advanced solid tumors or lymphomas.
Ulevostinag has been studied in two completed clinical trials: NCT04220866, a Phase 2 trial in head and neck squamous cell carcinoma, and NCT03010176, a Phase 1 trial in advanced solid tumors or lymphomas. Both trials have been completed.
Yes, Ulevostinag is also known as MK-1454. The two names refer to the same investigational drug developed by Merck & Company, Inc. (MRK).