An Open-label, Multicenter, Phase 1a/1b Study of IGM-8444 as a Single Agent and in Combination in Subjects With Relapsed, Refractory, or Newly Diagnosed Cancers
An Open-label, Multicenter, Phase 1a/1b Study of IGM-8444 as a Single Agent and in Combination in Subjects With Relapsed, Refractory, or Newly Diagnosed Cancers
Mechanism of Action
IGM-8444 is an agonist antibody to DRS on the cell surface. Binding of the antibody to DRS mimics the interaction between DRS and its natural ligand, TRAIL. Crosslinking activates the death receptor pathway leading to induction of apoptosis. Birinipant is a small molecule SMAC mimetic. SMAC is also an activator of apoptosis. Therefore, there could be a stronger apoptotic signal if the two agents are combined.
Purpose
- How much of the study agent alone or in combination with other drugs can be given with an acceptable level of side effects• The effects of the study agent alone or in combination with other drugs (good and bad)
- How much of the study agent alone or in combination with other drugs is absorbed into the blood and how fast it is removed
- How the body responds to the study agent alone or in combination with other drugs for a particular type of cancer
- ECOG Performance Status of 0 or 1
- Histologic documentation of incurable, locally advanced or metastatic tumor of the type being evaluated in individual cohorts.
- Adequate hepatic and renal function and adequate bone marrow reserve function.
- For combination cohorts, patients must be eligible to receive the chemotherapy or targeted agent.
- Ph1a only: No more than three prior therapeutic regimens.
- Ph1b only: Must be FOLFIRI naive subjects and must have received only 1 prior therapeutic regimen administered for the treatment of cancer in the advanced/metastatic setting.
- 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 or requiring anticonvulsants or corticosteroids for symptomatic control). Patients with a history of treated CNS metastases are eligible.
- Prior use of any chemotherapeutic agent or small molecule inhibitors (SMI) within 2 weeks or 5 half-lives, prior to the first dose of study treatment
- Treatment with a monoclonal antibody, or any other anticancer agent (including biologic, experimental, or hormonal therapy) investigational or otherwise, that is not chemotherapy or a SMI, within 4 weeks or five half-lives prior to first dose of study treatment.
- Ph1b: Subjects who have previously received FOLFIRI treatment for advanced or metastatic disease
Line of Therapy Restriction: FOLFIRI-naïve that received no more than 1 prior therapy in the advanced/metastatic setting
Location
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