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

Inclusion Criteria:

• Histologically or cytologically confirmed advanced malignancies as follows:

1. Part 1 only: Participants with the select advanced malignancies as specified inthe protocol.

2. Part 2 only:

• Cohort 1 only: Participants with Stage III (unresectable) or Stage IV (metastatic) melanoma that is considered nonamenable to curativetreatments or procedures.

• Cohort 2 only: Participants with histologically or cytologically confirmedrecurrent/metastatic SCCHN that is PD-L1 positive (CPS ≥ 1) which is notamenable to local therapy with curative intent.

• Participants must have experienced disease progression after treatment with standardtherapies, or are intolerant to or ineligible for standard treatment:

1. Part 1: All available standard therapies, including anti-PD-(L)1 andplatinum-based therapy, if applicable, that are known to confer clinicalbenefit. Prior anti-PD-(L)1 therapy should not have been discontinued becauseof intolerance.

2. Part 2: Available standard therapies, including anti-PD-(L)1 and platinum-basedtherapy, if applicable, that are known to confer clinical benefit. Prioranti-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 aadvanced/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 orexcisional).

• Part 2 only: Willingness to undergo a fresh tumor biopsy at screening andon-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 currentmalignancy, or any prior malignancy.

• Treatment with anticancer therapies or participation in another interventionalclinical 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 surgicalintervention before starting study treatment.

• Palliative radiation therapy administered within 1 week of first dose of studytreatment or radiation therapy in the thoracic region that is > 30 Gy within 6months 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, oractive, noninfectious pneumonitis.

• Active autoimmune disease requiring systemic immunosuppression with corticosteroids (> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within 2 yearsbefore 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 symptomsattributable to brain or CNS metastases).

• Chronic treatment with systemic steroids (> 10 mg/day of prednisone or equivalent).