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

Advanced Malignancies Clinical Trial

Official title:

A Phase 1, Open-Label, Multicenter Study of INCA32459 in Participants With Select Advanced Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05577182
• Other study ID #: INCA 32459-101
• Status: Recruiting
• Phase: Phase 1
• Start date: November 14, 2022
• Est. completion date: April 10, 2026

Study information

• Verified date: May 2024
• Source: Incyte Corporation
• Contact: Incyte Corporation Call Center (US)
• Phone: 1.855.463.3463
• Email: medinfo[@]incyte.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: April 10, 2026
• Est. primary completion date: April 10, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Advanced Malignancies
• Neoplasms

Intervention

Drug:
• INCA32459-101
solution for infusion

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Ucl Saint-Luc	Bruxelles
Belgium	Universitair Ziekenhuis Antwerpen (Uza)	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitair Ziekenhuis Brussel	Jette
Belgium	Chu Ucl Namur University Hospital Mont-Godinne	Yvoir
France	Centre Leon Berard	Lyon
France	Chu Hopital de La Timone	Marseille Cedex 5
France	Hospital Saint Louis	Paris
France	Institut Curie	Paris Cedex 05
France	Centre Eugene Marquis	Rennes Cedex
France	Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole	Toulouse
Italy	Comitato Etico Fondazione Irccs Istituto Nazionale Dei Tumori Milano	Milano
Italy	Istituto Nazionale Tumori Irccs Fondazione Pascale	Napoli
Italy	Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria Alle Scotte	Siena
Italy	Centro Ricerche Cliniche Di Verona (Crc)	Verona
Spain	Hospital Quironsalud Barcelona	Barcelona
Spain	Ico Institut Catala D Oncologia	L'hospitalet de Llobregat
Spain	Centro Integral Oncologico Clara Campal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Virgen de La Victoria	Málaga
Spain	Hospital Universitario Quironsalud Madrid	Pozuelo de Alarcón
Spain	Hospital General Universitario de Valencia	Valencia
United States	University of Texas Md Anderson Cancer Center	Houston	Texas
United States	The Angeles Clinic and Research Institute	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Belgium,  France,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Number of Participants with Dose Interruptions due to TEAE	Dose interruptions will occur according to protocol guidelines.	Up to approximately 12 months
Primary	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	Objective Response Rate (ORR)	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).	Up to 12 months
Secondary	Disease Control Response (DCR)	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).	Up to 12 months
Secondary	Duration of Response (DOR)	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.	Up to 12 months
Secondary	PK parameters: Cmax	Defined as the maximum (peak) plasma drug concentration	Up to 24 months
Secondary	PK parameters: tmax	Defined as the time to reach maximum (peak) plasma concentration following drug administration	Up to 24 months
Secondary	PK parameters: Cmin	Defined as concentration at the end of the dosing interval	Up to 24 months
Secondary	PK Parameters: AUC	Defined as the area under the plasma concentration-time curve	Up to 24 months
Secondary	PK Parameters: CL	Defined as the apparent total body clearance of the drug from plasma	Up to 24 months
Secondary	PK Parameters: Vz	Defined as apparent volume of distribution during terminal phase	Up to 24 months
Secondary	PK Parameters: t1/2	Defined as Elimination half-life (to be used in one-or noncompartmental model)	Up to 24 months
Secondary	Receptor Occupancy	Defined as PD-1 receptor occupancy in peripheral blood samples.	Up to 24 months