Phase 1a/1b Study of Aplitabart (IGM-8444) Alone or in Combination in Participants with Relapsed, Refractory, or Newly Diagnosed Cancers

Key Inclusion Criteria:

• Age ≥ 18 years at time of signing ICF

• ECOG Performance Status of 0 or 1

• Histologic documentation of incurable, locally advanced or metastatic tumor of thetype being evaluated in individual cohorts.

• Adequate hepatic and renal function and adequate bone marrow reserve function.

• For combination cohorts, participants must be eligible to receive the chemotherapyor targeted agent.

• Ph1a only: No more than three prior therapeutic regimens.

• Ph1b only: Must be FOLFIRI naïve participants and must have received only 1 priortherapeutic regimen administered for the treatment of cancer in theadvanced/metastatic setting - OR - FOLFIRI naïve participants that only receivedadjuvant therapy who progressed within six months after completing adjuvant therapy,and are confirmed to have locally advanced/metastatic disease

Key Exclusion Criteria:

• Inability to comply with study and follow-up procedures.

• Prior DR5 agonist therapy.

• Concomitant use of agents well-known to cause liver toxicity.

• Concomitant use of anti-cancer agents

• Palliative radiation to bone metastases within 2 weeks prior to Day 1.

• Major surgical procedure within 4 weeks prior to Day 1.

• Untreated or active central nervous system (CNS) metastases (progressing orrequiring anticonvulsants or corticosteroids for symptomatic control). Participantswith a history of treated CNS metastases are eligible.

• Prior use of any chemotherapeutic agent or small molecule inhibitors (SMI) within 2weeks or 5 half-lives, prior to the first dose of study treatment

• Treatment with a monoclonal antibody, or any other anticancer agent (includingbiologic, experimental, or hormonal therapy) investigational or otherwise, that isnot chemotherapy or a SMI, within 4 weeks or five half-lives prior to first dose ofstudy treatment.

• Ph1b: Participants who have previously received FOLFIRI treatment in the adjuvant,advanced, or metastatic disease setting