CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors

A Phase 1, First in Human Study of Adenovirally Transduced Autologous Macrophages Engineered to Contain an Anti-HER2 Chimeric Antigen Receptor in Subjects With HER2 Overexpressing Solid Tumors

Phase 1, first-in-human, open label study of CAR macrophages in HER2 overexpressing solid tumors.

A Phase 1, First in Human Study of Adenovirally Transduced Autologous Macrophages Engineered to Contain an Anti-HER2 Chimeric Antigen Receptor in Subjects with HER2 Overexpressing Solid Tumors

Main Study - Group 1 and Group 2 all HER2 overexpressing solid tumors

Intraperitoneal Substudy - HER2 overexpressing peritoneal disease

89[Zr] radiolabeled CT-0508 Substudy - All HER2 overexpressing solid tumors (Univ of Penn, Abramson Cancer Center only)

CT-0508 Combination with Pembrolizumab Substudy - All HER2 overexpressing solid tumors

Inclusion Criteria:

• HER2-positive recurrent or metastatic solid tumors for which there are no available curative treatment options.

  • Breast cancer and gastric/gastroesophageal junction cancers must have failed approved HER2-targeted agents.
  • Other HER2-positive tumor types must have failed standard of care therapies, while prior therapy with anti-HER2 drugs is not required.

• Subject must be willing and able to undergo tumor tissue biopsy procedures

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Subject has adequate bone marrow and organ function

Exclusion Criteria:

• HIV, active hepatitis B or hepatitis C infection.

• Diagnosis of immunodeficiency or chronic exposure to systemic corticosteroid therapy or any other form of immunosuppressive therapy

• Untreated or symptomatic central nervous system (CNS) metastases or cytology proven carcinomatous meningitis.

  o Subjects with small, asymptomatic CNS metastases that do not require treatment are permitted to enroll.

• Left ventricular ejection fraction (LVEF) <50% as determined by ECHO or multiple gated acquisition scan (MUGA)

Other protocol-defined Inclusion/Exclusion may apply.

CT-0508 in Combination with Pembrolizumab Substudy Only:

Exclusion Criteria:

• Subjects with severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
• Subjects with an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Subjects who have a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Subjects who have had an allogeneic tissue/solid organ transplant