IMA401 TCER® in Recurrent and/or Refractory Solid Tumors, Alone or in Combination With a Checkpoint Inhibitor

A Phase Ia/Ib First-In-Human Clinical Trial to Evaluate the Safety, Tolerability and Initial Anti-Tumor Activity of IMA401, a Bispecific T Cell Engaging Receptor Molecule (TCER®), as Monotherapy or in Combination With Checkpoint Inhibitor in Patients With Recurrent and/or Refractory Solid Tumors.

The goal of this clinical trial is to evaluate the safety, tolerability and initial anti-tumor activity of IMA401 as monotherapy or in combination with checkpoint inhibitor in patients with recurrent and/or refractory solid tumors.

Patients' HLA status and expression of the MAGE-A4 and/or MAGE-A8 target in the tumor must be confirmed.

Primary objective:

• To determine the maximum tolerated dose and/or recommended dose for extension for IMA401 as monotherapy and in combination with pembrolizumab

Secondary objectives:

• To characterize the safety and tolerability of IMA401 as monotherapy and in combination with pembrolizumab
• To evaluate initial anti-tumor activity of IMA401 as monotherapy and in combination with pembrolizumab
• To describe the pharmacokinetics of IMA401 as monotherapy and in combination with pembrolizumab

Inclusion Criteria:

• Patients must have voluntarily signed a written ICF, be able to understand and comply with clinical trial procedures
• Patients ≥ 18 years old
• Patients must have pathologically confirmed and documented advanced and/or metastatic NSCLC or HNSCC, other solid tumor may be considered
• Confirmed HLA status and IMA401 tumor target MAGE-A4 and/or MAGE-A8 expression
• Life expectancy > 2 months
• ECOG Performance Status of 0 to 1
• Measurable disease according to RECIST 1.1
• Adequate baseline hematologic, renal and hepatic function; acceptable coagulation status
• Patients must have recurrent and/or refractory solid tumors and must have received or not be eligible for all available indicated standard of care treatments
• The patient must have recovered from any side effects of prior therapy to Grade 1 or lower (except for non-clinically significant toxicities; e.g., alopecia, vitiligo) prior to treatment start. As determined by the investigator, the patient may still be eligible if the patient has not fully recovered from Grade ≥ 2 toxicities, in case if these toxicities are not anticipated to further improve (e.g., chronic peripheral neuropathy) and such toxicities are not anticipated to worsen with the IMA401 therapy

Exclusion Criteria:

• Other active malignancies that require treatment or that might interfere with the trial endpoints (ongoing adjuvant anti-hormonal treatment is allowed)
• History of hypersensitivity to components of IMA401, CPI treatment or rescue medications, contraindication for pembrolizumab
• Patients with prior allogeneic stem cell transplantation or organ transplantation
• Patients with autoimmune diseases needing disease-directed treatment
• Any serious or uncontrolled health condition, which, in the opinion of the Investigator, would place the subject at undue risk from the study, impair the ability of the subject to receive protocol specified therapy, or interfere with the interpretation of study results
• Positive for HIV or with active hepatitis B or C infection.
• Patients with active infection
• Systemic corticosteroids (≥ 10 mg/day prednisone or equivalent) received 2 weeks prior to starting trial treatment
• Patients with active central nervous system metastases and leptomeningeal metastases