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

NCT05577182 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: INCA 32459-1012022-501505-13-00
• Study Type: interventional
• Target: 46
• Locations: 4 countries
• Sites: 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

Keywords

LAG-3; bispecific antibody; melanoma; squamous cell carcinoma of the head and neck (SCCHN)

Outcome Measures

Primary Outcomes (4)

• Part 1: Occurrence of Dose Limiting Toxicities (DLTs)

  Toxicities occurring during Part 1 will define tolerability. DLTs will be assessed for severity by the investigator using CTCAE v5.0 criteria.

  Up to approximately 12 months

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  TEAE is any Adverse Event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug.

  Up to approximately 12 months

• Number of Participants with Dose Interruptions due to TEAE

  Dose interruptions will occur according to protocol guidelines.

  Up to approximately 12 months

• Number of Participants discontinue study due to TEAE

  TEAE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

  Up to approximately 12 months

Secondary Outcomes (11)

• Objective Response Rate (ORR)

  Up to 12 months

• Disease Control Response (DCR)

  Up to 12 months

• Duration of Response (DOR)

  Up to 12 months

• PK parameters: Cmax

  Up to 24 months

• PK parameters: tmax

  Up to 24 months

Study Arms (3)

Part 1: Dose Escalation

EXPERIMENTAL

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

Drug: INCA32459-101

Part 2: Dose Expansion Cohort Disease Group 1

EXPERIMENTAL

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

Drug: INCA32459-101

Part 2: Dose Expansion Cohort Disease Group 2

EXPERIMENTAL

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.

Drug: INCA32459-101

Interventions

INCA32459-101 DRUG

solution for infusion

Part 1: Dose Escalation; Part 2: Dose Expansion Cohort Disease Group 1; Part 2: Dose Expansion Cohort Disease Group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed advanced malignancies as follows:
• Part 1 only: Participants with the select advanced malignancies as specified in the protocol.
• 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:
• 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.
• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (13)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

University of Texas Md Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Cliniques Universitaires Ucl Saint-Luc

Brussels, 01200, Belgium

Location

Universitair Ziekenhuis Antwerpen (Uza)

Edegem, 02650, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 09000, Belgium

Location

Universitair Ziekenhuis Brussel

Jette, 01090, Belgium

Location

Chu Ucl Namur University Hospital Mont-Godinne

Yvoir, 05530, Belgium

Location

Centro Ricerche Cliniche Di Verona (Crc)

Verona, 37134, Italy

Location

Hospital Quironsalud Barcelona

Barcelona, 08023, Spain

Location

Ico Institut Catala D Oncologia

L'Hospitalet de Llobregat, 08906, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, 28223, Spain

Location

MeSH Terms

Conditions

Melanoma; Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 will be dose escalation using a statistical hybrid design to identify the RDE(s). Part 2 will be dose expansion portion which will administer the RDE(s) defined in Part 1 to participants in 2 tumor-specific cohorts.

Study Record Dates

• First Submitted: October 7, 2022
• First Posted: October 13, 2022
• Study Start: January 5, 2023
• Primary Completion: October 13, 2025
• Study Completion: October 13, 2025
• Last Updated: November 3, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (5); IT (1); US (2); ES (5)