Clinical trial NCT05577182: Study of INCA32459 a LAG-3 and PD-1 Bispecific Antibody in Participants With Select Advanced Malignancies
Official title: A Phase 1, Open-Label, Multicenter Study of INCA32459 in Participants With Select Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Malignancies
Keywords: LAG-3
bispecific antibody
melanoma
squamous cell carcinoma of the head and neck (SCCHN)
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2022-10-13
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Part 1: Occurrence of Dose Limiting Toxicities (DLTs)
timeFrame: Up to approximately 12 months
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 12 months
measure: Number of Participants with Dose Interruptions due to TEAE
timeFrame: Up to approximately 12 months
measure: Number of Participants discontinue study due to TEAE
timeFrame: Up to approximately 12 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 12 months
measure: Disease Control Response (DCR)
timeFrame: Up to 12 months
measure: Duration of Response (DOR)
timeFrame: Up to 12 months
measure: PK parameters: Cmax
timeFrame: Up to 24 months
measure: PK parameters: tmax
timeFrame: Up to 24 months
measure: PK parameters: Cmin
timeFrame: Up to 24 months
measure: PK Parameters: AUC
timeFrame: Up to 24 months
measure: PK Parameters: CL
timeFrame: Up to 24 months
measure: PK Parameters: Vz
timeFrame: Up to 24 months
measure: PK Parameters: t1/2
timeFrame: Up to 24 months
measure: Receptor Occupancy
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Houston
country: United States
facility: University of Texas Md Anderson Cancer Center
state: Texas
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Ucl Saint-Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen (Uza)
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Yvoir
country: Belgium
facility: Chu Ucl Namur University Hospital Mont-Godinne
city: Verona
country: Italy
facility: Centro Ricerche Cliniche Di Verona (Crc)
city: Barcelona
country: Spain
facility: Hospital Quironsalud Barcelona
city: L'hospitalet de Llobregat
country: Spain
facility: Ico Institut Catala D Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Pozuelo de Alarcón
country: Spain
facility: Hospital Universitario Quironsalud Madrid
Study officials:
References: