ADP-A2AFP / Adaptimmune - LARVOL DELTA

Phase I trial of ADP-A2AFP TCR T-cell therapy in patients with advanced hepatocellular or gastric hepatoid carcinoma. (PubMed, J Hepatol) - P1 | "Lymphodepletion chemotherapy followed by ADP-A2AFP TCR T-cell therapy showed a manageable safety profile and preliminary indications of antitumor activity in these previously treated patients."

Journal • P1 data • Gastric Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • Transplantation • AFP • CD8

AFPᶜ³³²T in Advanced HCC (clinicaltrials.gov) - P1 | N=39 | Completed | Sponsor: Adaptimmune | Active, not recruiting ➔ Completed

Trial completion • Cholangiocarcinoma • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • AFP

AFPᶜ³³²T in Advanced HCC (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Adaptimmune

New P1 trial • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • AFP

AFPᶜ³³²T in Advanced HCC (clinicaltrials.gov) - P1 | N=45 | Active, not recruiting | Sponsor: Adaptimmune | Trial completion date: Jul 2025 ➔ Dec 2025

Trial completion date • Cholangiocarcinoma • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • AFP

AFPᶜ³³²T in Advanced HCC (clinicaltrials.gov) - P1 | N=45 | Recruiting | Sponsor: Adaptimmune | N=24 ➔ 45

Enrollment change • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • AFP

AFPᶜ³³²T in Advanced HCC (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Adaptimmune | Trial completion date: Apr 2020 ➔ Jun 2026 | Trial primary completion date: Apr 2020 ➔ Jun 2021

Trial completion date • Trial primary completion date • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • AFP

AFPᶜ³³²T in Advanced HCC (clinicaltrials.gov) - P1 | N=45 | Active, not recruiting | Sponsor: Adaptimmune | Trial completion date: Jul 2036 ➔ Jul 2025

Trial completion date • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • AFP

AFPᶜ³³²T in Advanced HCC (clinicaltrials.gov) - P1 | N=45 | Active, not recruiting | Sponsor: Adaptimmune | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2026 ➔ Jul 2036

Enrollment closed • Trial completion date • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • AFP

Initial safety of AFP SPEAR T-cells in patients with advanced hepatocellular carcinoma (AACR 2019) - P1; "...Lymphodepletion is with fludarabine 20 mg/m2/day and cyclophosphamide 500 mg/m2/day on days -7 to -5... AFP SPEAR T-cells at the 0.1×109 cell dose show no evidence of on target or off target toxicity in the first 2 patients. No protocol defined DLTs were reported. Current data support continued investigation of AFPc332T-cells."

Clinical

OVERALL SAFETY AND EFFICACY FROM THE PHASE 1 TRIAL OF ADP-A2AFP SPEAR T-CELLS IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA OR OTHER CANCER TYPES EXPRESSING ALPHA-FETOPROTEIN (ILCA 2022) - P1 | "Pts received conditioning lymphodepletion with fludarabine and cyclophosphamide before infusion of ADP-A2AFP SPEAR T-cells. ADP-A2AFP SPEAR T-cell therapy has been well tolerated. Encouraging early evidence of efficacy was observed, including in pts who had progressed after multiple established therapies. A statistically significant difference in time from screening to ADP-A2AFP infusion between pts maintaining BORs ≥4 months vs <4 months was observed."

Clinical • Late-breaking abstract • P1 data • Atrial Fibrillation • Cardiovascular • Cytomegalovirus Infection • Gastrointestinal Cancer • Hematological Disorders • Hepatocellular Cancer • Hepatology • Infectious Disease • Inflammation • Neutropenia • Oncology • Septic Shock • Solid Tumor • AFP • HLA-A

AFPᶜ³³²T in Advanced HCC (clinicaltrials.gov) - P1; N=45; Recruiting; Sponsor: Adaptimmune; Trial primary completion date: Jun 2021 ➔ Sep 2023

Clinical • Trial primary completion date • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

ADP-A2AFP SPEAR T Cells Demonstrate Efficacy, Tolerability in Advanced HCC (Targeted Oncology) - P1 | N=45 | AFPᶜ³³²T in Advanced HCC (NCT03132792) | Adaptimmune | "Phase 1 data indicate that ADP-A2AFP SPEAR T cells are effective and tolerable in patients with advanced hepatocellular carcinoma....'SPEAR T cells up to doses of 10 billion transduced cells have been associated with an acceptable safety profile,' concluded Sangro. 'One patient had a sustained CR with normalization in serum α-fetoprotein, indicating as a proof-of-concept that this form of cell therapy can be active in the setting of advanced HCC. ADP-A2AFP SPEAR T-cells persisted in the periphery in a dose-dependent manner and were detected in post-infusion tumor tissue.'"

Media quote • P1 data

Adaptimmune Updates Data from its Phase 1 Trial for Liver Cancer at ILCA Showing Clinical Benefit (GlobeNewswire) - P1, N=45; NCT03132792; Sponsor: Adaptimmune Therapeutics plc; "Adaptimmune Therapeutics plc...announced updated data from its Phase 1 ADP-A2AFP trial for patients with liver cancer at ILCA...Thirteen patients with advanced hepatocellular carcinoma (HCC) received ADP-A2AFP in Cohort 3 and expansion The best overall responses in Cohort 3 and expansion (per RECIST v1.1) included 1 complete response (reported in 2020), 6 stable disease and 4 progressive disease. 2 patients did not have scan results at the time of data cut-off....The disease control rate for patients with at least one scan was 7/11 (64%) and 2 patients had stable disease lasting beyond 16 weeks Antitumor activity, with one complete response, sustained decreases in serum AFP, and best overall response of stable disease observed in 6 patients, indicate that ADP-A2AFP is an active product in HCC."

P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology

[VIRTUAL] Data from the third dose cohort and expansion phase of a Phase 1 trial of ADP-A2AFP SPEAR T-cells for patients with hepatocellular carcinoma and other cancer types expressing alpha-fetoprotein (ILCA 2021) - P1 | "Prior to ADP-A2AFP infusion, pts receive a lymphodepletion regimen including fludarabine 30 mg/m^2 once per day for 4 days and cyclophosphamide 600 mg/m^2 once per day for 3 days... ADP-A2AFP SPEAR T-cells for patients with HCC has been well tolerated. There have been no clear reports of T-cell-related on-target or off-target toxicity, and no protocol-defined doselimiting toxicities. There is promising early evidence of efficacy, and these data support continued investigation."

Clinical • P1 data • Gastrointestinal Cancer • Hematological Disorders • Hepatocellular Cancer • Hepatology • Inflammation • Leukopenia • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • AFP • HLA-A

Adaptimmune Reports Third Quarter Financial Results and Business Update (GlobeNewswire) - "Will initiate Phase 2 SURPASS-3 trial to investigate ADP-A2M4CD8 in ovarian cancer in 2022; Ceased enrollment in the SPEARHEAD-2 trial, and will evaluate the use of checkpoint inhibitors in combination with ADP-A2M4CD8; Data presented at ILCA from the ADP-A2AFP Phase 1 trial; screening will close in this trial; Allogeneic platform progress, including planning for IND submission in 2023 for first product targeting MAGE-A4 and opening a new allogeneic manufacturing facility in 2022."

IND • New P2 trial • P1 data • Trial status • Gynecologic Cancers • Head and Neck Cancer • Oncology • Ovarian Cancer • Sarcoma

[VIRTUAL] Updated data from an ongoing study with ADP-A2AFP spear T-cells (EASL-ILC-I 2020) - P1 | "Background and Aims: Genetically engineered affinity-enhanced autologous SPEAR T-cells (AFPc332T-cells) directed towards the HLA-A*02 are being tested in an ongoing Phase 1 trial to evaluate safety and antitumor activity in patients with hepatocellular carcinoma (HCC; NCT03132792)...In Cohorts 1 and 2, lymphodepletion consists of fludarabine (FLU) 20 mg/m2 and cyclophosphamide (CY) 500 mg/m2 QD for 3 days... ADP-A2AFP T-cells have shown no evidence of on target or off target toxicity in the first 5 patients with transduced cell doses up to 1.17 x 109 cells. No protocol-defined DLTs were reported. Current data support continued investigation of ADP-A2AFP in Cohort 3 with target transduced cell doses 5×109 cells (range 1.2 to 6.0 x 109)."

Gastrointestinal Cancer • Hematological Disorders • Hepatocellular Cancer • Hepatology • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia

Adaptimmune Reports Second Quarter Financial Results and Business Update (GlobeNewswire) - "On Sunday, September 5, 2021, Dr. Bruno Sangro of Clinica Universidad de Navarra will present data from Cohort 3 and the expansion phase of the Phase 1 trial of ADP-A2AFP in liver cancer during an oral presentation scheduled for 12:25 p.m. CET at the International Liver Cancer Association’s (ILCA) Annual Conference....The Company will present an update from its Phase 1 SURPASS trial in an e-poster at the European Society for Medical Oncology (ESMO) congress that will be available online September 16th."

P1 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology

Adaptimmune Reports First Quarter Financial Results and Business Update (GlobeNewswire) - "Planned data updates: SURPASS Phase 1 trial with ADP-A2M4CD8 (next-generation product targeting MAGE-A4) at European Society for Medical Oncology (ESMO) in September; ADP-A2AFP Phase 1 trial for people with liver cancer at the International Liver Cancer Association (ILCA) in September; Radiation sub-study of the ADP-A2M4 Phase 1 trial at American Society for Radiation Oncology (ASTRO) in October; Afami-cel translational data update at Society for Immunotherapy of Cancer (SITC) in November."

Clinical data • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology

Adaptimmune Reports Fourth Quarter / Full Year 2020 Financial Results and Business Update (GlobeNewswire) - “Additional clinical updates...September: update at International Liver Cancer Association (ILCA) conference for ADP-A2AFP Phase 1 trial for people with liver cancer; October: update at American Society for Radiation Oncology (ASTRO) for radiation sub-study of the ADP-A2M4 Phase 1 trial. November: ADP-A2M4 translational data update at Society for Immunotherapy of Cancer (SITC)."

Clinical data • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology

Adaptimmune to Showcase Market Potential for SPEAR T-cell Portfolio and Pipeline with Multiple Cell Therapy Platforms During Virtual Investor Day (GlobeNewswire) - “Driving towards delivery of two marketed products and two further BLAs by 2025: An overview of plans to launch the first TCR T-cell therapy (ADP-A2M4) in synovial sarcoma as enrollment in the SPEARHEAD-1 trial is on track; Plan to file a BLA with ADP-A2M4D8 in gastroesophageal cancers in 2024; Potential addressable population across all tumor types with significant MAGE-A4 expression of ~39,000 patients per year in the US and EU factored for HLA-A21; additional BLA(s) projected with ADP-A2M4CD8 in tumor types beyond gastroesophageal cancers; Additional BLA projected for ADP-A2AFP (first or next-generation CD8α) with a potential market opportunity of ~16,000 patients per year based on serum AFP expression1 and factoring for HLA-A2; Plan to incorporate next-generation CD8α enhancement into SPEAR T-cells targeting AFP in a clinical trial next year.”

BLA • Enrollment status • GastroEsophageal Cancer • Gastrointestinal Cancer • Oncology • Sarcoma

Promising Data from Phase 1 Trial with ADP-A2AFP in Liver Cancer at the International Liver Congress Confirm Safety Profile and Demonstrate Potential Benefit for Patients (GlobeNewswire) - P1, N=45; NCT03132792; Sponsor: Adaptimmune; "Adaptimmune Therapeutics plc...presented data from its Phase 1 trial with SPEAR T-cells targeting AFP at the virtual International Liver Congress (ILC). One patient out of four dosed with 5 billion or more cells had a complete response, which was reported previously. The data also demonstrate an acceptable safety profile in patients with hepatocellular carcinoma (HCC)....One patient had a complete response and also demonstrated a sustained reduction in serum AFP; ADP-A2AFP SPEAR T-cells were associated with an acceptable safety profile with no evidence of significant T-cell related hepatotoxicity and no protocol-defined dose limiting toxicities"

P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology

Adaptimmune Reports Q2 Financial Results and Business Update (GlobeNewswire) - "Update on ADP-A2AFP Phase 1 trial at the International Liver Congress to be held virtually from August 27 to 29…Updates on dose escalation cohorts from the SURPASS trial at a medical conference. Durability and translational data from patients with synovial sarcoma from the ADP-A2M4 Phase 1 trial at a medical conference….Protocol design for the Phase 2 trial with ADP-A2M4CD8 in gastroesophageal cancers has commenced and sites are being identified. The Company plans to initiate this trial in the first half of 2021."

New trial • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology

Adaptimmune Reports fourth quarter / full year 2019 financial results and business update (GlobeNewswire) - “The Company aims to launch ADP‑A2M4 for sarcoma in 2022; Planned 2020 milestones - First Half of 2020 : Full summary of the ADP-A2M4 Phase 1 trial at a medical conference; Safety update on Cohorts 1 and 2 of the ADP-A2AFP Phase 1 trial at a medical conference; Update on Cohort 3 of the ADP-A2AFP Phase 1 trial at a medical conference; Initiation of PD1 / PDL1 inhibitor combination trial with ADP-A2M4 in head & neck cancer; Data update from allogeneic program at a scientific meeting. Second Half of 2020: 12-month durability data from patients with synovial sarcoma from the ADP-A2M4 Phase 1 trial at a medical conference; Updates on dose escalation cohorts from the SURPASS trial at medical conferences; Update on the ADP-A2M4 Phase 1 radiation sub-study at a medical conference; Update on the ADP-A2AFP expansion cohort at a medical conference.”

Launch • New trial • P1 data

Adaptimmune Announces Oral Presentation of Allogeneic SPEAR T-cell Program at 2019 ASGCT Meeting (GlobeNewswire, Adaptimmune Therapeutics plc) - "Adaptimmune Therapeutics plc...announces an oral presentation by Dr. Jo Brewer, VP of Platform Sciences, summarizing data from Adaptimmune’s off‑the‑shelf SPEAR T-cell program at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting that will be held from April 29 to May 2, 2019 in Washington, DC...Oral presentation details:....Title: Differentiating T-Cells from Human induced pluripotent stem cells (hiPSCs) to Create Off-The-Shelf SPEAR T-Cell Therapies"

Preclinical

Cellular Biomedicine Group reports fourth quarter and full year 2018 financial results and recent operational progress (PRNewswire) - "2019 Anticipated Immuno-Oncology Key Milestones: Initiation of a Phase I clinical study of AFP-TCR for Hepatocellular carcinoma (HCC) in the U.S. and in China."

New P1 trial