ADP-A2M10 / Adaptimmune - LARVOL DELTA

[VIRTUAL] Phase I clinical trial evaluating the safety of ADP-A2M10 in patients with MAGE-A10+ head and neck, melanoma, or urothelial tumors (SITC 2020) - P1 | "Eligible pts underwent lymphodepletion with fludarabine and cyclophosphamide prior to receiving ADP-A2M10. Given the minimal antitumor activity and the discovery that MAGE-A10 expression frequently overlaps with MAGE-A4 expression, the clinical program has closed. Several trials with SPEAR T-cells targeting MAGE-A4 are ongoing (https://bit.ly/35htsZK)."

Clinical • IO biomarker • P1 data • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • MAGEA4

[VIRTUAL] Phase I clinical trial evaluating the safety of ADP-A2M10 SPEAR T-cells in patients with MAGE-A10+ advanced non-small cell lung cancer (SITC 2020) - P1 | "Pts underwent lymphodepletion (LD) with varying doses/schedules of fludarabine (Flu) and cyclophosphamide (Cy) prior to receiving ADP-A2M10. Given the minimal antitumor activity and the discovery that MAGE-A10 expression frequently overlaps with MAGE-A4 expression, the clinical program has closed. Several trials with SPEAR T-cells targeting MAGE-A4 are ongoing (https://bit.ly/35htsZK)."

Clinical • IO biomarker • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MAGEA4

Brief Communication on MAGE-A4 and Coexpression of Cancer Testis Antigens in Metastatic Synovial Sarcomas: Considerations for Development of Immunotherapeutics. (PubMed, J Immunother) - "Among MAGE-As, MAGE-A4 had the highest prevalence (65%), followed by MAGE-A10 (15%) and MAGE-A9 (13%)...Complementary immunohistochemical analyses were used to establish the positive correlation between RNA and protein expression for MAGE-A4 and NY-ESO-1. These data inform the strategy for optimal coverage of the SyS patient population with T-cell therapies, offering patients with SyS new options for single or combined second lines of treatment."

IO biomarker • Journal • Metastases • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Synovial Sarcoma • CTAG1B • MAGEA4 • PRAME

Selection of affinity-enhanced T-cell receptors for adoptive T-cell therapy targeting MAGE-A10 (AACR 2018) - P1; "The X-scan method permitted us to select the most specific and potent candidate for further pre-clinical testing. This MAGE-A10TCR is now being studied in clinical trials to treat HLA-A2+ patients with non-small cell lung cancer, urothelial cancers, melanoma, or head and neck cancers."

IO Biomarker • Bladder Cancer • Head and Neck Cancer • Melanoma • Non Small Cell Lung Cancer

Two phase I/II open label clinical trials evaluating the safety and efficacy of autologous T cells expressing enhanced TCRs specific for NY-ESO-1 or MAGE-A10 in subjects with stage IIIb or stage IV non-small cell lung cancer (NCT02588612/NCT02592577). (ASCO 2017) - P1/2,P=N/A; "These studies will evaluate the safety and antitumor activity of genetically engineered affinity enhanced TCRs (NY-ESO-1c259T or MAGE-A10c796T) directed towards a NYESO-1 or MAGE-A10 derived peptides complexed with HLA-A*02. The MAGE-A10c796T first-in-human study is a modified 3+3 design in up to 28 pt with escalating doses of 0.1, 1.0 and 1-6 x 109 transduced T cells, with staggered treatments to allow for safety review; dose escalation will be guided by the DLT observed and by safety review committee guidance. Response to treatment will be assessed by RECIST v1.1 at weeks 4, 8, 16, 24, every 3 months (for 2 yr) and every 6 months until disease progression."

Checkpoint inhibition • Clinical • P1/2 data • Biosimilar • Immunology • Non Small Cell Lung Cancer

A phase I single arm, open label clinical trial evaluating safety of MAGE-A10c796T in subjects with advanced or metastatic head and neck, melanoma, or urothelial tumors (NCT02989064). (ASCO 2017) - P=N/A,P1; "Disease assessments will be conducted at week 6, 12, 18 and 24, and then every 3 months until confirmation of disease progression. On study tumor biopsies and blood samples will be evaluated to compare the pre- and post-T cell infusion immune profile for association with treatment outcome."

Clinical • P1 data • Biosimilar • Bladder Cancer • Head and Neck Cancer • Melanoma

Structural insights into engineering a T-cell receptor targeting MAGE-A10 with higher affinity and specificity for cancer immunotherapy. (PubMed, J Immunother Cancer) - "Modest changes in engineered TCRs targeting MAGE-A10 produced significantly different properties. Conformational invariance of TCR and antigen peptide plus more space-filling CDR loop sequences may be desirable properties for clinically relevant TCR-pHLA systems to reduce the likelihood of structurally similar peptide mimics being tolerated by a TCR. Such properties may partially explain why the affinity-enhanced, in vitro-selected TCR has been generally well tolerated in patients."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor

Phase 1 Clinical Trial Evaluating the Safety and Anti-Tumor Activity of ADP-A2M10 SPEAR T-Cells in Patients With MAGE-A10+ Head and Neck, Melanoma, or Urothelial Tumors. (PubMed, Front Oncol) - P1 | "Patients underwent lymphodepletion with fludarabine and cyclophosphamide prior to receiving ADP-A2M10. Persistence of ADP-A2M10 in the peripheral blood and trafficking of ADP-A2M10 into the tumor was demonstrated. Because MAGE-A10 expression frequently overlaps with MAGE-A4 expression in tumors and responses were observed in the MAGE-A4 trial (NCT03132922), this clinical program closed, and trials with SPEAR T-cells targeting the MAGE-A4 antigen are ongoing."

IO biomarker • Journal • P1 data • Head and Neck Cancer • Hematological Disorders • Inflammation • Leukopenia • Melanoma • Neutropenia • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thrombocytopenia • Urothelial Cancer • HLA-A • MAGEA4

Engineering Cancer Antigen-Specific T Cells to Overcome the Immunosuppressive Effects of TGF-β. (PubMed, J Immunol) - "We previously generated specific peptide enhanced affinity receptor TCRs recognizing the HLA-A*02-restricted peptides New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/l-Ag family member-1A (TCR: GSK3377794, formerly NY-ESO-1) and melanoma Ag gene A10 (TCR: ADP-A2M10, formerly melanoma Ag gene A10). In this article, we show that exogenous TGF-β inhibited in vitro proliferation and effector functions of human T cells expressing these first-generation high-affinity TCRs, whereas inhibition was reduced or abolished in the case of second-generation TCRs coexpressed with dnTGFβRII (e.g., GSK3845097)...As an example, immunohistochemistry/RNAscope identified TGF-β-positive cells close to T cells in tumor nests and stroma, which had low frequencies of cells expressing IFN-γ in a non-small cell lung cancer setting. Coexpression of dnTGFβRII may therefore improve the efficacy of TCR-transduced T cells."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Hematological Disorders • Hematological Malignancies • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Synovial Sarcoma • CTAG1B • HLA-A • IFNG • TGFB1

Initial safety assessment of MAGE-A10c796TCR T-cells in two clinical trials. (ASCO 2018) - P1; "There was 1 DLT of G4 CRS in a patient with NSCLC that resolved with tocilizumab and steroids. MAGE-A10c796TCR T-cells at the 0.1109 transduced cell dose show no evidence of on target or off target toxicity. 1 DLT of CRS was observed. The available data support continued investigation of MAGE-A10c796TCR T-cells at higher doses."

Clinical • Melanoma • Non Small Cell Lung Cancer

MAGE A10ᶜ⁷⁹⁶T for Advanced NSCLC (clinicaltrials.gov) - P1; N=28; Completed; Sponsor: Adaptimmune; Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1 • ROS1

MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers (clinicaltrials.gov) - P1; N=10; Completed; Sponsor: Adaptimmune; Active, not recruiting ➔ Completed; Trial completion date: Nov 2034 ➔ Jun 2020

Clinical • Trial completion • Trial completion date • Bladder Cancer • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Adaptimmune Reports Q3 Financial Results and Business Update (GlobeNewswire) - “Four posters to be presented at the virtual SITC meeting (November 9-14) Poster entitled “Initial safety, efficacy, and product attributes from the SURPASS trial with ADP‑A2M4CD8…Two posters about the previously terminated ADP-A2M10 Phase 1 program: one for the lung cancer trial, and one for the triple tumor trial in melanoma, urothelial, and head & neck cancers. Durability of response data from patients with synovial sarcoma from the ADP-A2M4 Phase 1 trial to be presented in an oral presentation at the virtual CTOS conference…SPEARHEAD-1 is recruiting well and remains on target to complete enrollment in the first half of 2021. On track to start a Phase 2 trial with ADP-A2M4CD8 in gastroesophageal cancers (gastric, esophageal, and esophagogastric junction) in the first half of 2021.”

Enrollment status • New P2 trial • P1 data • Preclinical • Esophageal Cancer • Gastric Cancer • GastroEsophageal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Oncology • Sarcoma • Urothelial Cancer

Myxoid/round cell liposarcoma data with NY-ESO and MAGE-A10 study update to be presented at American Association for Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - "Data from the ongoing pilot study of NY-ESO SPEAR T-cells in myxoid/round cell liposarcoma (MRCLS) will be presented during an oral presentation ['Pilot Study of NY-ESO-1c259T Cells in Advanced Myxoid/Round Cell Liposarcoma']....In addition, data from Adaptimmune’s ongoing MAGE‑A10 pilot studies will be presented at a poster session['Initial safety assessment of MAGE-A10c796TCR T-cells in two clinical trials']."

Clinical data • Oncology • Sarcoma

Updated data from ongoing MAGE-A10 and MAGE-A4 studies presented at the 2018 ESMO Congress (GlobeNewswire) - "Data from the two ongoing MAGE-A10 studies ('triple tumor' [NCT02989064] and lung [NCT02592577]) are summarized below...In the 3 patients treated in Cohort 2 (all treated patients were in the NSCLC study)...1 patient died of pneumonia (unrelated to T-cell therapy), 1 patient had stable disease (SD) at Week 4, but then progressed [and]1 patient had SD at Weeks 4 and 8, but progressed at Week 12...Data from the ongoing MAGE-A4 'basket' [phase I] study [NCT03132922] in NSCLC, bladder, melanoma, synovial sarcoma, myxoid/round cell liposarcoma (MRCLS), head 1 patient with SD had an overall 27% reduction of target lesions observed at Week 6, and at the time of the second scan, which took place after the ESMO poster cut-off date, was assessed as PD."

P1 data • Bladder Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Thoracic Cancer • Urothelial Cancer

MAGE-A10: Initial efficacy and additional safety data from P1 pilot studies (NCT02592577, NCT02989064) for NSCLC and triple tumor in H2 2018 (Adaptimmune) - Q4 & FY 2017 Results

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

MAGE A10ᶜ⁷⁹⁶T for Advanced NSCLC (clinicaltrials.gov) - P1; N=28; Active, not recruiting; Sponsor: Adaptimmune; Trial completion date: Apr 2034 ➔ Dec 2034

Clinical • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Adaptimmune presents detailed safety update from ongoing MAGE-A10 pilot studies at ASCO (GlobeNewswire) - "A safety update from the two ongoing MAGE-A10 pilot studies [NSCLC study/NCT02592577; Triple Tumor Study/NCT02989064] was presented during a poster session (data cut-off 04 May 2018):...There were no deaths attributable to SPEAR T-cell therapy. To date, there has been no evidence of off-target toxicity. There were two events of cytokine release syndrome (CRS), both in the NSCLC study: one Grade 4 and oneGrade 1; both events resolved...Response data from these ongoing studies is anticipated throughout the remainder of 2018."

P1 data • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers (clinicaltrials.gov) - P1; N=10; Active, not recruiting; Sponsor: Adaptimmune; N=22 ➔ 10; Trial primary completion date: May 2020 ➔ Dec 2019

Clinical • Enrollment change • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Adaptimmune reports first quarter 2018 financial results and business update (GlobeNewswire) - "MAGE-A10: Dosing at one billion target cell dose in both pilot studies (NSCLC and 'triple tumor') [NCT02592577 and NCT02989064]; To date, no evidence of off-target toxicity in MAGE-A10 pilot studies in patients who received 100 million cells; Response data anticipated in the second half of 2018."

Enrollment status • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

MAGE-A10 TCR: Safety review for dose escalation of P1 trial (NCT02592577) in NSCLC in Q1 2018 (Adaptimmune) - Corporate Presentation

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

Adaptimmune announces favorable review of safety from one billion cell dose cohort in MAGE-A10 SPEAR T-cell study and initiation of third dosing cohorts (GlobeNewswire) - "Adaptimmune Therapeutics plc...announced favorable review of safety data from the second dose cohort of patients who received one billion transduced SPEAR T cells targeting MAGE-A10 in the non-small cell lung cancer (NSCLC) study...the Safety Review Committee (SRC) has endorsed dose escalation to the third dose cohorts in both MAGE-A10 pilot studies (i.e., the NSCLC and the triple tumor studies)....To date, eight patients have received 100 million transduced MAGE A10 SPEAR T-cells in the first dose cohorts of both studies [NSCLC study/NCT02592577; Triple Tumor Study/NCT02989064], and three patients have received one billion cells in the second cohort of the NSCLC study."

DSMB • Trial status • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers (clinicaltrials.gov) - P1; N=22; Active, not recruiting; Sponsor: Adaptimmune; Trial primary completion date: Nov 2019 ➔ May 2020

Clinical • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Mage-A10 TCR: Expiry of patents related to composition-of-matter in 2035 (Adaptimmune) - Annual Report 2019

Patent

Adaptimmune: Using TCRs to fight solid tumors (SeekingAlpha) - "Adaptimmune is developing TCRs to target solid tumors with key clinical data to be presented in the first half of 2020...ADP-A2M4 is also being evaluated in a Phase 1 trial for multiple solid tumors which is expected to run until the first half of 2020...To date, tumor shrinkage has been seen in lung cancer patients. However, the decision was made in August 2019 to deprioritize ADP-A2M10 for the corporate focus to be placed on current programs in ADP-A2M4 and ADP-A2AFP."

Clinical • Clinical data • Trial status