Anyara (naptumomab estafenatox) / Active Biotech, NeoTX - LARVOL DELTA

Naptumomab Estafenatox in Combination with Durvalumab in Subjects with Selected Advanced or Metastatic Solid Tumor, Including a Cohort Expansion in Esophageal Cancer. (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: NeoTX Therapeutics Ltd. | Active, not recruiting ➔ Recruiting | N=60 ➔ 120 | Trial completion date: Oct 2026 ➔ Mar 2027 | Trial primary completion date: Oct 2026 ➔ Mar 2027

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Cervical Cancer • Cervical Squamous Cell Carcinoma • Colorectal Cancer • Endometrial Adenocarcinoma • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • ER • HER-2 • TPBG

Clinical activity and safety of naptumomab estafenatox (NAP) and docetaxel in patients (pts) with checkpoint inhibitor (CPI) –pretreated advanced/metastatic non-small cell lung cancer (NSCLC): Preliminary results of a P2 trial. (ASCO 2024) - P2 | "Obinutuzumab pretreatment prior to cycle 1 used to inhibit anti-drug antibodies (ADAs) to NAP. These preliminary results of NAP + docetaxel show potential evidence of activity with acceptable safety in heavily pre-treated NSCLC pts. Further trials of NAP in combination, including CPIs are planned."

Checkpoint inhibition • Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Clinical activity and safety of naptumomab and docetaxel to be presented at ASCO 2024 (Active Biotech Press Release) - P2a | N=38 | NCT04880863 | Sponsor: NeoTX Therapeutics Ltd. | "Active Biotech...announces today that NeoTX Therapeutics, exclusive licensee of naptumomab estafenatox (naptumomab, NAP) from Active Biotech, will present initial results from phase IIa trial with NAP and docetaxel in advanced/metastatic Non-Small Cell Lung Cancer (NSCLC) patients, at the American Society of Clinical Oncology (ASCO) 2024...Five patients had partial response (PR), 2 of them unconfirmed, and overall response rate (ORR) was 16%. Two patients had prolonged responses: one lasted for 22 months and the second had complete response in target lesions lasting for 24 months despite CNS progression. One patient had initial pseudo-progression in target lesions with a subsequent PR, suggesting a possible immune response."

P2a data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Naptumomab Estafenatox in Combination With Pembrolizumab Preceded by Obinutuzumab in Patients With Urothelial Cancers (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Weill Medical College of Cornell University | N=30 ➔ 0 | Initiation date: Jun 2023 ➔ Nov 2023 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Aug 2024 ➔ Dec 2025

Combination therapy • Enrollment change • Trial initiation date • Trial primary completion date • Trial withdrawal • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Naptumomab Estafenatox in Combination With Durvalumab in Subjects With Selected Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: NeoTX Therapeutics Ltd. | Phase classification: P1b ➔ P1 | Trial completion date: Aug 2025 ➔ Oct 2026 | Trial primary completion date: May 2025 ➔ Oct 2026

Phase classification • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Adenocarcinoma • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Adenocarcinoma • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • ER • HER-2 • TPBG

NT-NAP-102-1: Naptumomab Estafenatox (NAP) in Combination With Docetaxel Following Obinutuzumab Pretreatment in Subjects With Checkpoint Inhibitor Pretreated Advanced or Metastatic NSCLC (clinicaltrials.gov) - P2 | N=38 | Completed | Sponsor: NeoTX Therapeutics Ltd. | Active, not recruiting ➔ Completed | Phase classification: P2a ➔ P2 | Trial completion date: Jul 2024 ➔ Jan 2024

Phase classification • Trial completion • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Naptumomab Estafenatox in Combination With Durvalumab in Subjects With Selected Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1b | N=60 | Active, not recruiting | Sponsor: NeoTX Therapeutics Ltd. | Trial completion date: Aug 2023 ➔ Aug 2025 | Trial primary completion date: May 2023 ➔ May 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Adenocarcinoma • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Adenocarcinoma • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • ER • HER-2 • TPBG

Tumor targeted superantigen (TTS) enhances CAR-T cell activity against solid tumors in vivo (SITC 2023) - P1b, P2a | "These results provide valuable insights for the development of improved strategies combining TTS with CAR-T therapy, paving the way for enhanced treatment options in solid tumors. The 5T4-targeted TTS, naptumomab estafenatox, is currently being evaluated in clinical studies in combination with durvalumab [NCT03983954] and docetaxel [NCT04880863]."

CAR T-Cell Therapy • Preclinical • Oncology • Solid Tumor

NT-NAP-102-1: Naptumomab Estafenatox (NAP) in Combination With Docetaxel Following Obinutuzumab Pretreatment in Subjects With Checkpoint Inhibitor Pretreated Advanced or Metastatic NSCLC (clinicaltrials.gov) - P2a | N=38 | Active, not recruiting | Sponsor: NeoTX Therapeutics Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2023 ➔ Jul 2024 | Trial primary completion date: Oct 2023 ➔ Jan 2024

Checkpoint inhibition • Combination therapy • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Naptumomab Estafenatox in Combination With Pembrolizumab Preceded by Obinutuzumab in Patients With Urothelial Cancers (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Weill Medical College of Cornell University

Combination therapy • New P1 trial • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Safety and preliminary activity of naptumomab estafenatox (NAP) and durvalumab in patients with advanced or metastatic solid tumors: interim results from a phase 1b trial (AACR 2023) - P1b | "Obinutuzumab pretreatment was employed to inhibit the formation of anti-drug antibodies (ADAs) to NAP. NAP RP2D was reached at 10 mcg/kg. Antitumor activity with significant response duration was observed. Based on the favorable safety profile and prolonged responses, including CRs, in patients where response from a single agent CPI may not be expected, further evaluation of this combination is warranted including patients who have received prior CPI therapy."

Clinical • IO biomarker • Metastases • P1 data • Breast Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Mesothelioma • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor

Clinical Trial Poster Presentation of Naptumomab at AACR 2023 Annual Meeting (Market Screener) - "Active Biotech...announced the acceptance of an abstract at the American Association for Cancer Research (AACR) 2023 Annual Meeting in Orlando, Florida, April 14-19, 2023. The poster will present the results of safety and preliminary activity in the phase 1b dose escalation trial of naptumomab (naptumomab estafenatox, NAP) combined with durvalumab in patients with advanced or metastatic solid tumors."

P1 data • Bladder Cancer • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hepatocellular Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Kidney Cancer • Liver Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer

Tumor-targeted superantigens produce curative tumor immunity with induction of memory and demonstrated antigen spreading. (PubMed, J Transl Med) - "These new results indicate that TTSs not only can turn a "cold" tumor into a "hot" tumor but also can enable epitope spreading and memory response, which makes TTSs ideal candidates for combination with ICB agents and other anticancer agents."

IO biomarker • Journal • Immune Modulation • Oncology • Solid Tumor

Naptumomab Estafenatox in Combination With Durvalumab in Subjects With Selected Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1b | N=60 | Active, not recruiting | Sponsor: NeoTX Therapeutics Ltd. | Trial completion date: May 2023 ➔ Aug 2023

Combination therapy • Metastases • Trial completion date • Bladder Cancer • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Adenocarcinoma • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Adenocarcinoma • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • ER • HER-2 • TPBG

Selective T cells Redirection Proteins (STR) Enhance the Anti-Tumor Activity of Checkpoint Inhibitors (CPIs) and can Lead to Long-Lasting Immunity Against the Tumor (SITC 2019) - P1b; "Background: Tumor-targeted superantigens (TTS) such as Naptumomab Estafenatox (Nap) are fusion proteins that consist of genetically engineered Superantigens (Sag) linked to Fragment antigen binding (Fab) moieties directed to tumor-associated antigens. Our studies show that combination of CPI with STR overcomes the limited effect of CPI monotherapy regardless of tumor antigen expression level. In addition, our in vivo studies demonstrate that the combination of STR with CPI may lead to long term durable responses not possible in most patients receiving single agent CPI therapy. Moreover, the ability of these "cured mice" to reject tumor re-challenge suggests that STRs cause release of secondary antigens that prime subsequent immune responses."

Checkpoint inhibition • IO biomarker • PD(L)-1 Biomarker • Oncology • Solid Tumor

Tumor Targeted Superantigen (TTS), Naptumomab Estafenatox (NAP), enhances CAR-T cells potency and can boost CAR-T efficacy against solid tumors (SITC 2021) - P1b, P2a | "Background CAR-T therapy has limited efficacy against solid tumors due to low trafficking to the tumor, limited cell expansion in patients, tumor antigen heterogeneity, and an immunosuppressive microenvironment. The ability of NAP administration to activate T cells outside of the immunosuppressive microenvironment (in the lymphoid organs), promote T cell infiltration into the tumor and induce long-term memory responses, strongly suggests that combination of CAR-T cells with NAP may overcome the limited effect of CAR-T therapy against solid tumors. NAP is currently being evaluated in clinical studies in combination with durvalumab [NCT03983954] and docetaxel [NCT04880863]."

CAR T-Cell Therapy • Clinical • IO biomarker • Oncology • Solid Tumor • CCR7 • FAS • HER-2 • IFNG • IL2RA • LAMP1 • TNFRSF9

Naptumomab Estafenatox in Combination With Durvalumab in Subjects With Selected Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1b | N=60 | Active, not recruiting | Sponsor: NeoTX Therapeutics Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Bladder Cancer • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Adenocarcinoma • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Adenocarcinoma • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • ER • HER-2 • TPBG

NT-NAP-102-1: Naptumomab Estafenatox (NAP) in Combination With Docetaxel Following Obinutuzumab Pretreatment in Subjects With Checkpoint Inhibitor Pretreated Advanced or Metastatic NSCLC (clinicaltrials.gov) - P2a | N=35 | Recruiting | Sponsor: NeoTX Therapeutics Ltd. | Trial primary completion date: Jun 2023 ➔ Oct 2023

Checkpoint inhibition • Combination therapy • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Naptumomab Estafenatox in Combination With Durvalumab in Subjects With Selected Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1b | N=50 | Recruiting | Sponsor: NeoTX Therapeutics Ltd. | Trial completion date: Jul 2022 ➔ Mar 2023 | Trial primary completion date: Apr 2022 ➔ Dec 2022

Combination therapy • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Adenocarcinoma • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Adenocarcinoma • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • ER • HER-2 • TPBG

Successful completion of the first stage of the phase IIa clinical trial of naptumomab in combination with docetaxel and the study is now enrolling into the second stage (GlobeNewswire) - "Active Biotech...and its partner NeoTX announce today the successful completion of the first stage of a Simon 2 stage phase IIa clinical trial of naptumomab estafenatox (NAP, naptumomab), in combination with docetaxel in patients with advanced or metastatic non-small cell lung cancer (NSCLC) who have been previously treated with chemotherapy and checkpoint inhibitors (CPIs). In the study, the patients are treated with NAP for 4 consecutive days and with docetaxel at a standard dose on day 5 in 21-day treatment cycles. The first stage of this trial required a minimum of two responses out of ten patients to move to the second stage of the trial, which is now enrolling."

Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Data on Naptumomab Estafenatox (NAP) Enhancing CAR-T cells Potency Presented by NeoTX at SITC 2021 Annual Meeting (PRNewswire) - "NeoTX presented data that shows that NAP generates more potent CAR-T cells and acts synergistically against tumor cell lines in vitro. NAP is a fusion protein that consists of genetically engineered Superantigens (Sag) linked to Fragment antigen-binding (Fab) moieties directed to tumor-associated antigens, turns 'cold tumors hot' and, in preclinical models, can lead to long-term memory responses."

Preclinical • Oncology • Solid Tumor

Active Biotech’s partner NeoTX to Present at the Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire) - "The poster presentation will highlight preclinical data demonstrating that naptumomab enhances CAR-T cells potency and can boost CAR-T efficacy against solid tumors."

Preclinical • Oncology • Solid Tumor

Active Biotech and NeoTX today announce that the first patient has been enrolled in the phase IIa clinical trial of naptumomab estafenatox in combination with docetaxel in patients with advanced non-small cell lung cancer (NSCLC) (GlobeNewswire) - "Active Biotech...and its partner NeoTX announce today that the first patient has been enrolled in the phase IIa clinical trial of naptumomab estafenatox (naptumomab), in combination with docetaxel in patients with advanced non-small cell lung cancer (NSCLC)."

Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Naptumomab Estafenatox in Combination With Durvalumab in Subjects With Selected Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1b; N=50; Recruiting; Sponsor: NeoTX Therapeutics Ltd.; Trial completion date: Feb 2022 ➔ Jul 2022; Trial primary completion date: Nov 2021 ➔ Apr 2022

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Adenocarcinoma • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • GastroEsophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Adenocarcinoma • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • ER • HER-2 • MRI • TPBG

NT-NAP-102-1: Naptumomab Estafenatox (NAP) in Combination With Docetaxel Following Obinutuzumab Pretreatment in Subjects With Checkpoint Inhibitor Pretreated Advanced or Metastatic NSCLC (clinicaltrials.gov) - P2a; N=35; Recruiting; Sponsor: NeoTX Therapeutics Ltd.; Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Clinical • Combination therapy • Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR