ABL103 in Combination With Pembrolizumab, With or Without Taxane in Advanced or Metastatic Solid Tumors

Official title

A Multicenter, Open-label, Phase 1b/2 Trial of ABL103, a Bispecific Antibody of B7-H4 and 4-1BB, in Combination With Pembrolizumab With/Without Taxane in Subjects With Selected, Progressive, Locally Advanced (Unresectable) or Metastatic Solid Tumors

Overview

This study is to assess the safety and antitumor activity of ABL103 plus pembrolizumab, with or without taxane, in advanced or metastatic solid tumors.

Interventions

• Drug ABL103
  IV infusion
• Drug KEYTRUDA® (pembrolizumab)
  IV infusion
• Drug Taxane
  IV infusion

Primary outcome measures

• Incidence of Dose-Limiting Toxicities (DLTs) [Time frame: Day 1 to Day 21 (Safety Lead-in Part 1) and Day 1 to Day 28 (Safety Lead-in Part 2)]
• Incidence of Treatment-Emergent Adverse Events (TEAEs), Treatment-Related AEs, Serious AEs (SAEs), and Infusion-Related Reactions (IRRs) [Time frame: From baseline through study completion, an average of 12 months]
• Recommended Dose for Expansion (RDE) Determination [Time frame: From baseline through study completion, an average of 12 months]
• Objective Response Rate (ORR) [Time frame: Up to approximately 30 months]
• Disease Control Rate (DCR) [Time frame: Up to approximately 30 months]

Secondary outcome measures (3)

• Preliminary Objective Response Rate (ORR) [Time frame: Up to approximately 30 months]
• Preliminary Disease Control Rate (DCR) [Time frame: Up to approximately 30 months]
• Incidence of Anti-Drug Antibodies (ADA) [Time frame: From baseline through study completion, an average of 12 months]

Eligibility criteria

Inclusion criteria

• Subject must understand and be willing to provide informed consent and be able to comply with the study procedures and restrictions.
• Subjects must be ≥18 years of age on the day of signing the informed consent form (ICF).
• Subject must have a histologically or cytologically confirmed locally advanced unresectable, or metastatic solid tumor.
• Subject must be relapsed or be refractory to available standard therapy or they must be intolerant of available standard therapy.
• Subject must meet Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 assessed 7 days before the first administration of the study drug.
• Subjects must be recovered from AEs from prior therapy to Grade 1 or the baseline grade more than 14 days prior to the first administration of the study drug, except alopecia or Grade 2 toxicities that are deemed stable or irreversible (e.g., peripheral neuropathy)
• Subjects who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Subject with endocrine-related AEs who are adequately treated with hormone replacement or subjects who have ≤Grade 2 neuropathy are eligible.
• Subjects must have adequate hematologic, renal, hepatic, and thyroid function at screening and within 7 days prior to the first administration of study drug.
• Female subjects who are not surgically sterile or postmenopausal must agree to use a highly effective method of birth control (2 methods strongly recommended) during the study and for 6 months following the last dose of ABL103/pembrolizumab.
• Female subjects of childbearing potential must have a negative serum pregnancy test at screening and within 7 days prior to Cycle 1 Day 1 (C1D1).
• Male subjects with female partner(s) of childbearing potential must agree to use contraception and and must not donate sperm during the treatment period with ABL103 and taxane and for at least 6 months after the final administration of ABL103 and taxane.
• Male subjects with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom throughout the study period, and for at least 6 months after the final administration of ABL103 and taxane, and during the partner's pregnancy or breastfeeding period. When using a male condom, the partner must also use an additional method of contraception acceptable for female subjects.

Exclusion criteria

• Subject has received prior anticancer monoclonal antibody treatment or investigational therapy (agent or device) for which the pharmacologic or toxicity profile is not expected to have resolved prior to the first administration of the study drug. A minimum of 28 days is generally recommended for agents with known delayed toxicities or prolonged biological activity, unless otherwise justified.
• Subject has received prior radiotherapy within 2 weeks of the first administration of study drug, or has radiation-related toxicities, requiring corticosteroids.
• Subject has received any prior immunotherapy and was discontinued from the treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis.
• Subject has received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study treatment.
• Subject has risk factors for bowel obstruction or bowel perforation, including, but not limited to a history of acute diverticulitis, intra-abdominal abscess, and abdominal carcinomatosis. Subjects with ovarian cancer with a history of abdominal carcinomatosis can be enrolled.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 4 centers

• Seoul National University Bundang Hospital — Seongnam
• Seoul National University Hospital — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul

United States · 1 center

• UH Cleveland Medical Center — Cleveland

Australia · 1 center

• PASO Medical — Frankston

Identifiers

NCT: NCT07158918 · ABL103-1002 · KEYNOTE-G16 · MK-3475-G16

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗