car-macrophages for the treatment of her2 overexpressing solid tumors

Conditions: HER2-positive; Adenocarcinoma; Bile Duct Cancer; Biliary Tract Cancer; Bladder Cancer; Breast Cancer; Breast Neoplasm; Carcinoma, Ductal; Carcinoma, Hepatocellular; Cancer; Lung Cancer, Non-Small-Cell; Carcinoma, Ovarian Epithelial; Carcinoma, Small Cell; Carcinoma, Squamous; Carcinoma, Transitional Cell; Colorectal Cancer; Esophagogastric Junction Neoplasms; Inflammatory Breast Cancer; Stomach Neoplasms; Malignant Neoplasms; Ovarian Neoplasms; Pancreatic Cancer; HER2-positive Solid Tumors; HER2-positive Breast Cancer; HER2-positive Gastric Cancer; HER-2 Protein Overexpression; HER-2 Gene Amplification; Prostate Cancer; Head and Neck Cancer; Endometrial Cancer; Lung Cancer, Small Cell

Summary: 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

Eligibility criteria:
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

Keywords: her2-positive solid tumors phase 1 cell therapy car-macrophage immunotherapy advanced cancer post menopausal premenopausal metastatic cancer prostate cancer head and neck cancer lung cancer, small cell endometrial cancer lung cancer, non-small cell