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

Phase 1

Active, not recruiting

• Conditions: Advanced Malignancies
• Interventions: Drug: INCA32459-101

• Registration Number: NCT05577182
• Lead Sponsor: Incyte Corporation

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-10-07
• Study First Submitted QC: 2022-10-10
• Study First Posted: 2022-10-13
• Study Start: 2023-01-05
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-11
• Last Update Posted: 2025-03-12
• Primary Completion: 2026-08-03
• Study Completion: 2026-08-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 120

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 2: Dose Expansion Cohort Disease Group 1	INCA32459-101	INCA32459 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for unresectable or metastatic melanoma.
Part 1: Dose Escalation	INCA32459-101	INCA32459 will be administered at a protocol defined starting regimen intravenously. Subsequent dose regimens will be determined during study conduct.
Part 2: Dose Expansion Cohort Disease Group 2	INCA32459-101	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.

Primary Outcome Measures

Name	Time	Method
Part 1: Occurrence of Dose Limiting Toxicities (DLTs)	Up to approximately 12 months	Toxicities occurring during Part 1 will define tolerability. DLTs will be assessed for severity by the investigator using CTCAE v5.0 criteria.
Number of Participants with Dose Interruptions due to TEAE	Up to approximately 12 months	Dose interruptions will occur according to protocol guidelines.
Number of Participants discontinue study due to TEAE	Up to approximately 12 months	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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	Up to approximately 12 months	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.

Secondary Outcome Measures

Name	Time	Method
PK Parameters: AUC	Up to 24 months	Defined as the area under the plasma concentration-time curve
PK Parameters: Vz	Up to 24 months	Defined as apparent volume of distribution during terminal phase
Objective Response Rate (ORR)	Up to 12 months	Defined as having Complete Response (CR) or Partial Response (PR), as determined by the investigator by radiographic disease assessment according to RECIST v1.1 or Lugano criteria (B-cell lymphomas only).
Disease Control Response (DCR)	Up to 12 months	Defined as having CR, PR, or Stable Disease (SD) as determined by the investigator by radiographic disease assessment according to RECIST v1.1. or Lugano criteria (B-cell lymphomas only).
PK parameters: Cmax	Up to 24 months	Defined as the maximum (peak) plasma drug concentration
PK Parameters: CL	Up to 24 months	Defined as the apparent total body clearance of the drug from plasma
Duration of Response (DOR)	Up to 12 months	Defined as the time from earliest date of disease response (Completed Response or Partial Response) until earliest date of disease progression as determined by the investigator by radiographic disease assessment according to RECIST v1.1 or Lugano criteria (B-cell lymphomas only) or death due to any cause if occurring sooner than progression.
PK parameters: tmax	Up to 24 months	Defined as the time to reach maximum (peak) plasma concentration following drug administration
PK parameters: Cmin	Up to 24 months	Defined as concentration at the end of the dosing interval
PK Parameters: t1/2	Up to 24 months	Defined as Elimination half-life (to be used in one-or noncompartmental model)
Receptor Occupancy	Up to 24 months	Defined as PD-1 receptor occupancy in peripheral blood samples.

Trial Locations

Locations (13)

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; 🇧🇪 Bruxelles, Belgium

Universitair Ziekenhuis Antwerpen (Uza); 🇧🇪 Edegem, Belgium

Chu Ucl Namur University Hospital Mont-Godinne; 🇧🇪 Yvoir, Belgium

Centro Ricerche Cliniche Di Verona (Crc); 🇮🇹 Verona, Italy

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

Universitair Ziekenhuis Brussel; 🇧🇪 Jette, Belgium

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