Undisclosed HER2Bi-armed ATC / TransTarget, Barbara Ann Karmanos Cancer Institute - LARVOL DELTA

Targeted T Cells After Neoadjuvant Chemotherapy in Treating Women With Stage II or III Breast Cancer Undergoing Surgery (clinicaltrials.gov) - P2 | N=8 | Terminated | Sponsor: Barbara Ann Karmanos Cancer Institute | Unknown status ➔ Terminated; Primary co-investigator leaving the institution & funding transfer.

Surgery • Trial termination • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Pembro and HER2Bi-Armed Activated T Cells in Treating Patients With Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=15 | Completed | Sponsor: Barbara Ann Karmanos Cancer Institute | Active, not recruiting ➔ Completed | Trial completion date: Jun 2023 ➔ Nov 2022

Trial completion • Trial completion date • Genito-urinary Cancer • Immune Modulation • Oncology • Prostate Cancer • Solid Tumor

Phase II trial of a novel immunotherapy combination of pembrolizumab and HER2 bi-armed activated T cells (BATs) in metastatic castrate resistant prostate cancer. (ASCO-GU 2020) - P2; " mCRPC patients with 0-1 performance status (PS) and normal liver, kidney and marrow function, pre or post docetaxel chemotherapy were eligible. The combination regimen of pembrolizumab and BATs appears to be worthy of future exploration in a larger trial in mCRPC. Clinical trial information: NCT03406858. Research Funding: Merck Inc and NIH Cancer Center Support Grant CA-22453, Pharmaceutical/Biotech Company, U.S. National Institutes of Health."

IO biomarker • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HER-2

Laboratory-Treated T Cells After Second-Line Chemotherapy in Treating Patients With HER2/Neu-Negative Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=43 | Terminated | Sponsor: Barbara Ann Karmanos Cancer Institute | N=63 ➔ 43 | Unknown status ➔ Terminated

Enrollment change • Metastases • Trial termination • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2

Phase II Trial of Pembrolizumab and Anti-CD3 x Anti-HER2 Bispecific Antibody-Armed Activated T Cells in Metastatic Castration-Resistant Prostate Cancer (Clin Cancer Res) - P2 | N=15 | NCT03406858 | "Fourteen patients were enrolled with a median age of 69 (range 57–82 years) and median PSA of 143.4 (range 8.2–4210 ng/dL)....The toxicities were grade1–2 infusion reactions with fever, chills, headaches, nausea and/or myalgias. Primary endpoint of 6 month PFS was achieved in 5 of 14 patients (38.5%; 95% confidence interval, 19.5%–76.5%). Median PFS was 5 months and median survival was 31.6 months....The safety and promising efficacy makes this combination worthy of future investigation in mCRPC."

P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Pembro and HER2Bi-Armed Activated T Cells in Treating Patients With Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=15 | Active, not recruiting | Sponsor: Barbara Ann Karmanos Cancer Institute | Recruiting ➔ Active, not recruiting | N=33 ➔ 15 | Trial completion date: Dec 2021 ➔ Jun 2023

Checkpoint inhibition • Enrollment change • Enrollment closed • Trial completion date • Genito-urinary Cancer • Immune Modulation • Inflammation • Oncology • Prostate Cancer • Solid Tumor • CAST

Phase II trial of Pembrolizumab and Anti-CD3 x Anti-HER2 Bispecific Antibody Armed Activated T Cells in Metastatic Castrate Resistant Prostate Cancer (Clin Cancer Res) - P2 | N=33 | NCT03406858 | "A phase II study was conducted to evaluate the safety and efficacy of the combination of HER2 BATs and...pembrolizumab....Fourteen patients were enrolled with a median age of 69 (range 57-82 years) and median PSA of 143.4 (range 8.2 – 4210 ng/dL)....The toxicities were grade1-2 infusion reactions with fever, chills, headaches, nausea and/or myalgias. Primary endpoint of 6 month progression free survival (PFS) was achieved in 5 of 14 patients (38.5%, 95%CI 19.5%-76.5%). Median PFS was 5 months and median survival was 31.6 months....The safety and promising efficacy makes this combination worthy of future investigation in mCRPC."

P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Pembrolizumab and HER2Bi-Armed Activated T Cells in Treating Patients With Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P2; N=33; Recruiting; Sponsor: Barbara Ann Karmanos Cancer Institute; Trial completion date: Jan 2021 ➔ Dec 2021; Trial primary completion date: Jan 2021 ➔ Dec 2021

Checkpoint inhibition • Clinical • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Immune Modulation • Inflammation • Oncology • Prostate Cancer • Solid Tumor

Phase II trial of a novel immunotherapy combination of pembrolizumab and HER2 bi-armed activated T cells (BATs) in metastatic castrate resistant prostate cancer. (ASCO-GU 2020) - P2; " mCRPC patients with 0-1 performance status (PS) and normal liver, kidney and marrow function, pre or post docetaxel chemotherapy were eligible. The combination regimen of pembrolizumab and BATs appears to be worthy of future exploration in a larger trial in mCRPC. Clinical trial information: NCT03406858. Research Funding: Merck Inc and NIH Cancer Center Support Grant CA-22453, Pharmaceutical/Biotech Company, U.S. National Institutes of Health."

IO Biomarker • P2 data • HER-2

Activated T-cell Therapy, Low-Dose Aldesleukin, and Sargramostim in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That is Stage III-IV, Refractory, or Recurrent (clinicaltrials.gov) - P1; N=20; Recruiting; Sponsor: Barbara Ann Karmanos Cancer Institute

Clinical • New P1 trial • Breast Cancer • Fallopian Tube Cancer • HER2 Breast Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor • HER-2 • IFNG

Activated T-cell Therapy, Low-Dose Aldesleukin, and Sargramostim in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That is Stage III-IV, Refractory, or Recurrent (clinicaltrials.gov) - P1; N=0; Withdrawn; Sponsor: Barbara Ann Karmanos Cancer Institute; N=20 ➔ 0; Recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Breast Cancer • Fallopian Tube Cancer • HER2 Breast Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor • HER-2 • IFNG

T Cell Mediated Adaptive Therapy for Her2-positive Neoplasms of Digestive System (clinicaltrials.gov) - P1; N=6; Enrolling by invitation; Sponsor: Yi Miao

IO biomarker • New P1 trial • Colorectal Cancer • Esophageal Cancer • Gallbladder Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Liver Cancer • Oncology • Pancreatic Cancer • Solid Tumor • HER-2

Laboratory Treated T Cells After Chemotherapy in Treating Patients With HER2-Negative Stage II-III Breast Cancer That Can Be Removed By Surgery (clinicaltrials.gov) - P2; N=48; Recruiting; Sponsor: Barbara Ann Karmanos Cancer Institute

Clinical • New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Male Breast Cancer • Oncology • Solid Tumor • HER-2

Targeted T Cells After Neoadjuvant Chemotherapy in Treating Women With Stage II or III Breast Cancer Undergoing Surgery (clinicaltrials.gov) - P2; N=8; Active, not recruiting; Sponsor: Barbara Ann Karmanos Cancer Institute; Trial completion date: Jun 2017 ➔ Dec 2018

Clinical • Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Targeted T Cells After Neoadjuvant Chemotherapy in Treating Women With Stage II or III Breast Cancer Undergoing Surgery (clinicaltrials.gov) - P2; N=32; Suspended; Sponsor: Barbara Ann Karmanos Cancer Institute; Trial primary completion date: Apr 2016 ➔ Jun 2017

Clinical • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Targeted T Cells After Neoadjuvant Chemotherapy in Treating Women With Stage II or III Breast Cancer Undergoing Surgery (clinicaltrials.gov) - P2; N=8; Active, not recruiting; Sponsor: Barbara Ann Karmanos Cancer Institute; Suspended ➔ Active, not recruiting; N=32 ➔ 8

Clinical • Enrollment change • Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Targeted T Cells After Neoadjuvant Chemotherapy in Treating Women With Stage II or III Breast Cancer Undergoing Surgery (clinicaltrials.gov) - P2; N=32; Recruiting; Sponsor: Barbara Ann Karmanos Cancer Institute; Trial primary completion date: Jun 2015 ➔ Apr 2016

Clinical • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Targeted T Cells After Neoadjuvant Chemotherapy in Treating Women With Stage II or III Breast Cancer Undergoing Surgery (clinicaltrials.gov) - P2; N=32; Suspended; Sponsor: Barbara Ann Karmanos Cancer Institute; Recruiting ➔ Suspended

Clinical • Trial suspension • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Targeted T Cells After Neoadjuvant Chemotherapy in Treating Women With Stage II or III Breast Cancer Undergoing Surgery (clinicaltrials.gov) - P2; N=32; Recruiting; Sponsor: Barbara Ann Karmanos Cancer Institute; N=48 ➔ 32

Clinical • Enrollment change • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Pembrolizumab and HER2Bi-Armed Activated T Cells in Treating Patients With Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P2; N=33; Recruiting; Sponsor: Barbara Ann Karmanos Cancer Institute; Trial completion date: Dec 2019 ➔ Jan 2021; Trial primary completion date: Dec 2019 ➔ Jan 2021

Checkpoint inhibition • Clinical • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Immune Modulation • Inflammation • Oncology • Prostate Cancer • Solid Tumor

Enhanced cytotoxicity against solid tumors by bispecific antibody-armed CD19 CAR T cells: a proof-of-concept study. (PubMed, J Cancer Res Clin Oncol) - "HER2Bi- or EGFRBi-armed CART19 exhibited specific cytotoxicity against multiple HER2/EGFR/CD19 tumor targets in overnight and long-term serial killing assays. CART19 showed improved survival and were resistant to exhaustion after prolonged repeated exposure to tumor cells."

CAR T-Cell Therapy • Journal • Breast Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Thoracic Cancer

Superior anti-tumor activity of metabolically enhanced bispecific antibody armed CAR-less Bionic T cells (SITC 2019) - "Sequential killing by HER2Bi armed BTC followed by (f/b) EGFRBi armed BTC showed efficient killing against target cells (86.2%) or EGFRBi-BTC f/b HER2Bi-BTC (88.2%) compared to the killing by HER2Bi-BTC (49.7%) or EGFRBi-BTC (43.5%) alone at low E/T ratio in the presence of 100 IU/ml IL-2 at 96 hours... Data show that armed BTC: 1) exhibit superior survival in hypoxic condition; 2) can effectively kill multiple tumor targets in serial killing assay; 3) cytokines and chemokines show immune modulating and tumor killing profile."

IO Biomarker