A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies

Primary Outcome Measures

• Number of treatment-emergent adverse events [ Time Frame: Up to 12 months ]
  Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.

• Maximum tolerated dose or pharmacologically active dose (PAD) of INCAGN02390 (Part 1 only) [ Time Frame: Up to approximately 1 month ]
  PAD defined as a dose that achieves a level of receptor occupancy considered to be biologically active.

Secondary Outcome Measures

• Cmax of INCAGN02390 [ Time Frame: Up to 12 months ]
  Maximum observed plasma or serum concentration.

• Tmax of INCAGN02390 [ Time Frame: Up to 12 months ]
  Time to maximum concentration.

• Cmin of INCAGN02390 [ Time Frame: Up to 12 months ]
  Minimum observed plasma or serum concentration over the dose interval.

• AUC0-t of INCAGN02390 [ Time Frame: Up to 12 months ]
  Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t.

• Objective response rate [ Time Frame: Up to 12 months ]
  Defined as the percentage of participants having complete response (CR) or partial response (PR) determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

• Duration of response [ Time Frame: Up to 12 months ]
  Defined as time from earliest date of disease response (CR or PR) until earliest date of disease progression (determined by investigator assessment of radiographic disease per RECIST v1.1) or death from any cause, if occurring sooner than progression.

• Disease control rate [ Time Frame: Up to 12 months ]
  Defined as percentage of participants having CR, PR, or stable disease as best on-study response.

• Progression-free survival [ Time Frame: Up to 12 months ]
  Defined as the time from date of first dose of study drug until the earliest date of disease progression (determined by investigator assessment of objective radiographic disease per RECIST v1.1) or death from any cause if occurring sooner than progression.

• Level of binding of INCAGN02390 to TIM-3 [ Time Frame: Up to approximately 3 months ]
  Assessed from participant whole blood samples.

• Immunogenicity of INCAGN02390 [ Time Frame: Up to 12 months ]
  Defined as the occurrence of specific ADA to INCAGN02390.

Inclusion Criteria

Participants with locally advanced or metastatic tumors who are not eligible for any available therapy likely to convey clinical benefit (locally advanced disease must not be amenable to resection with curative intent).

Participants who have disease progression after treatment with available therapies that are known to confer clinical benefit or who are intolerant to treatment.

Willingness and ability to safely undergo pretreatment and on-treatment tumor biopsies (core or excisional).

Eastern Cooperative Oncology Group performance status 0 or 1.

Willingness to avoid pregnancy or fathering children based on protocol-defined criteria.

Exclusion Criteria

Laboratory values at screening outside the protocol-defined ranges.

Administration of colony-stimulating factors within 14 days before Study Day 1.

Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live-attenuated vaccines and are not allowed.Receipt of anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug.

Receipt of a live vaccine within 30 days of planned start of study drug.

Active autoimmune disease that required systemic treatment in the past (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).

Known active central nervous system metastases and/or carcinomatous meningitis.

Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the participant has been disease-free for > 1 year, after treatment with curative intent.

Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.

Active infection requiring systemic therapy.

Evidence of active HBV or HCV infection.

Known history of HIV (HIV 1/2 antibodies).

Known allergy or reaction to any component of study drug or formulation components.

Prior treatment with an anti-TIM-3 antibody for any indication.