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Phase 1 Completed N=156 Treatment

Study of Ulevostinag (MK-1454) Alone or in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors or Lymphomas (MK-1454-001)

Source: ClinicalTrials.gov NCT03010176 ↗
Enrolled (actual)
156
Serious AEs
44.1%
Results posted
Feb 2024
Primary outcomePrimary: Part 1: Percentage of Participants Who Experienced a Dose-limiting Toxicity (DLT) Per Common Terminology Criteria for Adverse Events, Version 4.0 (CTCAE 4.0) — 15.1; 10.4; 0 Percentage of participants

Summary

The purpose of this study is to identify a maximum tolerated dose (MTD) or maximum administered dose (MAD) of ulevostinag alone and of ulevostinag in combination with pembrolizumab in participants with advanced/metastatic solid tumors or lymphomas in Part 1, and to evaluate the safety and efficacy of ulevostinag via intratumoral (IT) injection in combination with pembrolizumab in selected solid tumors in Part 2. Ulevostinag will be administered IT; pembrolizumab (pembro) will be administered via intravenous (IV) infusion. In Part 1, participants will be allocated to one of three treatment arms: ulevostinag monotherapy (cutaneous/subcutaneous [cut/subcut] lesions), ulevostinag +pembro (cut/subcut lesions), or ulevostinag +pembro (visceral lesions). In Part 2, participants with head and neck squamous cell carcinoma (HNSCC) who are anti-programmed cell death-protein 1 or anti-programmed cell death-ligand 1 (anti-PD-1/PD-L1) refractory or with anti-PD-1/PD-L1 treatment (TrT)-naïve triple-negative breast cancer (TNBC) or with anti-PD-1/PD-L1 TrT-naïve solid tumors with liver metastases/lesions will receive ulevostinag via IT injection at the preliminary Recommended Phase 2 Dose (RP2D) determined in Part 1 PLUS pembrolizumab via IV infusion for up 35 cycles (up approximately 2 years).

Outcome Measures

OutcomeResultp-value
PRIMARY
Part 1: Percentage of Participants Who Experienced a Dose-limiting Toxicity (DLT) Per Common Terminology Criteria for Adverse Events, Version 4.0 (CTCAE 4.0)
15.1; 10.4; 0
PRIMARY
Parts 1 and 2: Number of Participants Who Experienced One or More Adverse Events (AEs)
32; 66; 26; 21; 25
PRIMARY
Parts 1 and 2: Number of Participants Who Discontinued Study Drug Due to an AE
3; 7; 3; 3; 2
SECONDARY
Parts 1 and 2: Ulevostinag Area Under the Plasma Drug Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
8.62; 6.59; 5.88; 6.24; 7.98
SECONDARY
Parts 1 and 2: Ulevostinag Minimum Plasma Concentration (Cmin)
0.18; 0.12; 0.08; 0.09; 0.13
SECONDARY
Parts 1 and 2: Ulevostinag Maximum Plasma Concentration (Cmax)
6.56; 5.38; 7.08; 6.75; 8.4
SECONDARY
Parts 1 and 2: Pembrolizumab Minimum Plasma Concentration (Cmin)
14.5; 14.25; 17.7; 13.6
SECONDARY
Parts 1 and 2: Objective Response Rate (ORR) As Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
0.0; 16.1; 3.8; 4.8; 4.0

Eligibility Criteria

Inclusion Criteria

All Arms and Cohorts (Parts 1 and 2):

  • Has ≥1 injectable lesion which is measurable and amenable to injection and biopsy.
  • Has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
  • Demonstrates adequate organ function within 7 days prior to treatment initiation.
  • Female participants of childbearing potential must be using a contraceptive method that is highly effective or be abstinent from heterosexual intercourse (on a long-term and persistent basis) during the intervention period and for at least 130 days after the last dose of study intervention and agrees not to donate eggs to others or freeze/store for personal use for the purpose of reproduction during this period. Male participants must agree to refrain from donating sperm PLUS either be abstinent from heterosexual intercourse (on a long-term and persistent basis) OR agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse contraception, unless confirmed to be azoospermic (vasectomized) during the intervention period and for at least 130 days after the last dose of study intervention.
  • Human Immunodeficiency (HIV)-infected participants must meet these additional criteria: a) Has laboratory-test-documented HIV-1 infection; b) Has well-controlled HIV on anti-retroviral therapy (ART), defined as: 1) must have a cluster of differentiation (CD4+) T-cell count >350 cells/mm^3 at time of screening; 2) must have achieved and maintained virologic suppression defined as confirmed HIV ribonucleic acid (RNA) level below 50 or the lower limit of quantification (LLOQ) using the locally available assay at the time of screening and for ≥12 weeks prior to screening; and, 3) must have been on a stable regimen, without changes in drugs or dose modification, for ≥4 weeks prior to study entry (Day 1).

All Part 1 Arms:

-Has ≥1 distant, discrete non-injected lesion which is amenable to biopsy. This lesion must be measurable as defined by the response criteria used to assess the participant (RECIST 1.1 for solid tumors or revised International Working Group [IWG] criteria for lymphomas).

Part 1 Arm 1: Ulevostinag (Cut/Subcut Lesions) and Part 1 Arm 2: Ulevostinag+Pembro (Cut/Subcut Lesions):

  • Has a histologically- or cytologically-confirmed advanced/metastatic solid tumor or lymphoma by pathology report and who has received, or been intolerant to, all treatment known to confer clinical benefit. Solid tumors and lymphomas of any type are eligible for enrollment.
  • Has stage III or stage IV disease that is not surgically resectable. Stage IIB (T3N0M0B0-1) cutaneous T cell lymphoma (CTCL) participants are eligible.

Part 1 Arm 3: Ulevostinag+Pembro (Visceral Lesions):

  • Has stage III or stage IV disease that is not surgically resectable.
  • Has metastatic liver involvement that does not exceed one third of the total liver volume in participants to be treated by liver IT injection. Hepatocellular carcinoma participants are excluded from eligibility of IT liver injection.

All Part 2 Expansion Cohorts:

Part 2 Cohort A: HNSCC Anti-PD-1/PD-L1 Refractory:

  • Has HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx; anti-PD-1/PD-L1 refractory metastatic or recurrent. Participants may not have a primary tumor site of the nasopharynx (any histology).
  • Has histologically confirmed Stage III, IVa, or IVb disease per TNM (Tumor, Nodes, Metastasis) staging, American Joint Committee on Cancer (AJCC, 8th edition), with recurrent or persistent disease after definitive chemoradiation, deemed unresectable and considered refractory to both platinum-based combination chemotherapy and anti-programmed cell death-ligand 1 (anti-PD-1/PD-L1) antibody therapy.

OR

  • Has histologically confirmed Stage IVc disease per TNM staging, AJCC 8th edition, considered refractory to platinum-based combination chemotherapy and anti-PD-1/PD-L1 antibody therapy.

Part 2 Cohort B: Anti-PD-1/PD-L1 TrT-Naï

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03010176). 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.

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