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

Sponsor

Incyte Corporation (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05577182

Collaborator

(none)

120

Enrollment

Locations

Arms

40.8

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignancies	Drug: INCA32459-101	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 14, 2022

Anticipated Primary Completion Date :

Apr 10, 2026

Anticipated Study Completion Date :

Apr 10, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Dose Escalation INCA32459 will be administered at a protocol defined starting regimen intravenously. Subsequent dose regimens will be determined during study conduct.	Drug: INCA32459-101 solution for infusion
Experimental: 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.	Drug: INCA32459-101 solution for infusion
Experimental: 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.	Drug: INCA32459-101 solution for infusion

Arm

Intervention/Treatment

Experimental: Part 1: Dose Escalation

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

Drug: INCA32459-101

solution for infusion

Experimental: 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.

Drug: INCA32459-101

solution for infusion

Experimental: 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.

Drug: INCA32459-101

solution for infusion

Outcome Measures

Primary Outcome Measures

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 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.
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.

Secondary Outcome Measures

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).
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: Cmax [Up to 24 months]
Defined as the maximum (peak) plasma drug concentration
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: AUC [Up to 24 months]
Defined as the area under the plasma concentration-time curve
PK Parameters: CL [Up to 24 months]
Defined as the apparent total body clearance of the drug from plasma
PK Parameters: Vz [Up to 24 months]
Defined as apparent volume of distribution during terminal phase
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Angeles Clinic and Research Institute	Los Angeles	California	United States	90025
2	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-4206
3	University of Texas Md Anderson Cancer Center	Houston	Texas	United States	77030
4	Universitair Ziekenhuis Brussel	Brussel		Belgium	01090
5	Cliniques Universitaires Ucl Saint-Luc	Bruxelles		Belgium	01200
6	Universitair Ziekenhuis Antwerpen (Uza)	Edegem		Belgium	02650
7	Universitair Ziekenhuis Gent	Gent		Belgium	09000
8	Chu Ucl Namur University Hospital Mont-Godinne	Yvoir		Belgium	05530
9	Hospital Quironsalud Barcelona	Barcelona		Spain	08023
10	Ico Institut Catala D Oncologia	L'hospitalet de Llobregat		Spain	08908
11	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
12	Centro Integral Oncologico Clara Campal	Madrid		Spain	28050
13	Hospital Universitario Virgen de La Victoria	Mï¿½LAGA		Spain	29010
14	Hospital Universitario Quironsalud Madrid	Pozuelo DE ALARCï¿½N		Spain	28223
15	Hospital General Universitario de Valencia	Valencia		Spain	46014

Sponsors and Collaborators

Incyte Corporation

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Incyte Corporation

ClinicalTrials.gov Identifier:

NCT05577182

Other Study ID Numbers:

INCA 32459-101

First Posted:

Oct 13, 2022

Last Update Posted:

Dec 2, 2022

Last Verified:

Dec 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Incyte Corporation

LAG-3

bispecific antibody

melanoma

squamous cell carcinoma of the head and neck (SCCHN)

Additional relevant MeSH terms:

Neoplasms

Study Results

No Results Posted as of Dec 2, 2022