Study of INCA32459 a LAG-3 and PD-1 Bispecific Antibody in Participants With Select Advanced Malignancies

NCT ID: NCT05577182

Last Updated: 2025-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-05
• Study Completion Date: 2025-10-13

Brief Summary

This is a multicenter, open-label, single-arm study to investigate the safety, tolerability, PK, pharmacodynamics and preliminary activity of INCA32459 in participants with selected advanced malignancies. Part 1 (dose escalation) will determine the recommended dose of INCA 32459 for expansion (RDE) and the maximum tolerated dose (MTD). Part 2 (dose expansion) will further evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary antitumor activity of INCA 32459 at the recommended dose(s) for expansion in 2 tumor-specific cohorts.

Conditions

Advanced Malignancies

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Dose Escalation

INCA32459 will be administered at a protocol defined starting regimen intravenously. Subsequent dose regimens will be determined during study conduct.

Group Type: EXPERIMENTAL

INCA32459-101

Intervention Type: DRUG

solution for infusion

Part 2: Dose Expansion Cohort Disease Group 1

INCA32459 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for unresectable or metastatic melanoma.

Group Type: EXPERIMENTAL

INCA32459-101

Intervention Type: DRUG

solution for infusion

Part 2: Dose Expansion Cohort Disease Group 2

INCA32459 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) that is PD-L1 positive.

Group Type: EXPERIMENTAL

INCA32459-101

Intervention Type: DRUG

solution for infusion

Interventions

INCA32459-101

solution for infusion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed advanced malignancies as follows:

1. Part 1 only: Participants with the select advanced malignancies as specified in the protocol.

2. Part 2 only:

• Cohort 1 only: Participants with Stage III (unresectable) or Stage IV (metastatic) melanoma that is considered nonamenable to curative treatments or procedures.
• Cohort 2 only: Participants with histologically or cytologically confirmed recurrent/metastatic SCCHN that is PD-L1 positive (CPS ≥ 1) which is not amenable to local therapy with curative intent.
• Participants must have experienced disease progression after treatment with standard therapies, or are intolerant to or ineligible for standard treatment:

1. Part 1: All available standard therapies, including anti-PD-(L)1 and platinum-based therapy, if applicable, that are known to confer clinical benefit. Prior anti-PD-(L)1 therapy should not have been discontinued because of intolerance.

2. Part 2: Available standard therapies, including anti-PD-(L)1 and platinum-based therapy, if applicable, that are known to confer clinical benefit. Prior anti-PD-(L)1 therapy should not have been discontinued because of intolerance. Part 2 participants may have received up to 2 prior systemic therapies in the a advanced/metastatic setting.

• ECOG performance status of 0 or 1
• Part 2 only: Measurable disease according to RECIST v1.1.
• Part 2 only: Willingness to undergo a fresh tumor biopsy at screening (core or excisional).
• Part 2 only: Willingness to undergo a fresh tumor biopsy at screening and on-treatment in selected participant.
• Willingness to avoid pregnancy or fathering children

Exclusion Criteria

• Prior treatment with any LAG-3- or MHC Class II-directed therapy for current malignancy, or any prior malignancy.
• Treatment with anticancer therapies or participation in another interventional clinical study within 28 days before the first administration of study treatment (this includes curative radiation to the thorax or systemic anticancer therapies).
• Not recovered to ≤ Grade 1 or baseline from residual toxicities of prior therapy (with exceptions specified in the protocol).
• Not recovered adequately from toxicities and/or complications from surgical intervention before starting study treatment.
• Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy in the thoracic region that is > 30 Gy within 6 months of the first dose of study treatment.
• Any known additional malignancy that is progressing or requires active treatment; history of other malignancy within 3 years of the first dose of study treatment (with exceptions specified in the protocol).
• Evidence of interstitial lung disease or history of interstitial lung disease, or active, noninfectious pneumonitis.
• Active autoimmune disease requiring systemic immunosuppression with corticosteroids (> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within 2 years before the first dose of study treatment.
• Untreated brain or CNS metastases or brain or CNS metastases that have progressed (eg, evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain or CNS metastases).
• Chronic treatment with systemic steroids (> 10 mg/day of prednisone or equivalent).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Angeles Clinic and Research Institute

Los Angeles, California, United States

University of Texas Md Anderson Cancer Center

Houston, Texas, United States

Cliniques Universitaires Ucl Saint-Luc

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen (Uza)

Edegem, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Universitair Ziekenhuis Brussel

Jette, , Belgium

Chu Ucl Namur University Hospital Mont-Godinne

Yvoir, , Belgium

Centro Ricerche Cliniche Di Verona (Crc)

Verona, , Italy

Hospital Quironsalud Barcelona

Barcelona, , Spain

Ico Institut Catala D Oncologia

L'Hospitalet de Llobregat, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Centro Integral Oncologico Clara Campal

Madrid, , Spain

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, , Spain

Countries

United States; Belgium; Italy; Spain

Other Identifiers

2022-501505-13-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

INCA 32459-101

Identifier Type: -

Identifier Source: org_study_id