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=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

Dose escalation in liver cancer study with ADP-A2AFP (AFP) SPEAR T-cells and moving to expansion phase in ADP-A2M10 (MAGE-A10) lung cancer study after favorable safety reviews (GlobeNewswire) - "Adaptimmune Therapeutics plc...announced that the Safety Review Committee (SRC) has endorsed dose escalation in the ongoing ADP-A2AFP (AFP) study in patients with hepatocellular carcinoma (liver cancer) to the second dose cohort. The SRC has also endorsed moving to the expansion phase of the ADP-A2M10 (MAGE-A10) lung cancer study....Across both studies, most adverse events have been consistent with those typically experienced by cancer patients undergoing cytotoxic chemotherapy or other cancer immunotherapies with no evidence of alloreactivity or toxicity related to off-target binding."

DSMB • P1 data