OBT076 / Menarini, Oxford BioTherap - LARVOL DELTA

AdCC_2023-01: Study of OBT076 Associated or Not in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma of the Head and Neck (clinicaltrials.gov) - P1 | N=19 | Terminated | Sponsor: Groupe Oncologie Radiotherapie Tete et Cou | Completed ➔ Terminated; toxicity

IO biomarker • Trial termination • Adenoid Cystic Carcinoma • Head and Neck Cancer • Oncology

Preliminary activity and safety of OBT076 in patients with CD205 positive solid tumors: Results from the phase 1b part C sequential expansion cohort (AACR 2025) - "This open label Phase 1B study (Part C) aimed to evaluate the safety and preliminary efficacy of sequential therapy OBT076 followed by anti-PD-1 balstilimab in patients with CD205 positive (2+ in ≥ 50% by IHC) solid tumors.Key eligibility criteria included age ≥ 18, CD205 positivity, ECOG ≤1, and progression on/after standard treatments. OBT076 demonstrated manageable safety profile, neutropenia and febrile neutropenia were the most frequent Grade 3-4 AEs. No clinically relevant ocular events have been reported.Preliminary activity with PRs was seen in GEJ cancer and bladder cancer. Insufficient activity in terms of PFS prolongation does not support further investigation of sequential short-course OBT076 followed by checkpoint inhibitors."

Clinical • P1 data • Adenoid Cystic Carcinoma • Bladder Cancer • Esophageal Cancer • Gastric Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • LY75

Preliminary activity and safety of OBT076 in patients with CD205 positive solid tumors: Results from the phase 1b part B expansion cohort (AACR 2025) - "Pts who had been previously treated with anti-PD-1 directed therapy had the option to be re-challenged after progression on OBT076 with anti-PD-1 balstilimab. OBT076 demonstrated a manageable safety profile. Neutropenia and febrile neutropenia were most frequent grade 3-4 AEs. No clinically relevant ocular events have been reported."

Clinical • P1 data • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • LY75

AdCC_2023-01: Study of OBT076 Associated or Not in Patients with Recurrent or Metastatic Adenoid Cystic Carcinoma of the Head and Neck (clinicaltrials.gov) - P1 | N=19 | Completed | Sponsor: Groupe Oncologie Radiotherapie Tete et Cou | Suspended ➔ Completed | N=32 ➔ 19 | Trial completion date: Sep 2027 ➔ Oct 2024 | Trial primary completion date: Sep 2026 ➔ Oct 2024

Enrollment change • IO biomarker • Metastases • Trial completion • Trial completion date • Trial primary completion date • Adenoid Cystic Carcinoma • Head and Neck Cancer • Oncology

Oxford BioTherapeutics to Present at World ADC Conference 2024 (GlobeNewswire) - "Dr. Haeske will be a featured guest speaker, diving into the science behind combination therapy strategies and highlighting the potential of OBT’s first-in-class lead asset, OBT076, an innovative ADC being developed for the treatment of advanced solid tumors...In addition, Dr. Yu-Tzu Tai, Associate Director of ADC & Translational Research at OBT, will be presenting the company’s advanced discovery platform, OGAP-Verify, and its enhanced capacity to identify novel, cancer-specific targets for the development of first-in-class therapies, particularly ADCs, T-cell engagers and other therapeutic antibodies, addressing unmet clinical needs in oncology."

Clinical • Solid Tumor

AdCC_2023-01: Study of OBT076 Associated or Not in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma of the Head and Neck (clinicaltrials.gov) - P1 | N=32 | Suspended | Sponsor: Groupe Oncologie Radiotherapie Tete et Cou | Recruiting ➔ Suspended

IO biomarker • Metastases • Trial suspension • Adenoid Cystic Carcinoma • Head and Neck Cancer • Oncology

Oxford BioTherapeutics Announces First Patient Dosed with OBT076 in Phase 1b Trial in Adenoid Cystic Carcinomas of the Head and Neck (GlobeNewswire) - "Oxford BioTherapeutics...today announces that the first patient has been dosed in a Phase 1b trial investigating OBT’s lead candidate, OBT076, in patients with Adenoid Cystic Carcinoma (ACC) of the head and neck...the trial (NCT05930951) will be carried out in patients with recurrent or metastatic ACC of the head and neck from an anticipated 15 study sites across the GORTEC network in France, Belgium and Switzerland."

Trial status • Adenoid Cystic Carcinoma • Head and Neck Cancer

AdCC_2023-01: Study of OBT076 Associated or Not in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma of the Head and Neck (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Groupe Oncologie Radiotherapie Tete et Cou | Not yet recruiting ➔ Recruiting

Enrollment open • Adenoid Cystic Carcinoma • Head and Neck Cancer • Oncology

Safety and Preliminary Efficacy of OBT076 in Recurrent/Metastatic CD205+ Solid Tumors (clinicaltrials.gov) - P1 | N=200 | Recruiting | Sponsor: Oxford BioTherapeutics Ltd | N=150 ➔ 200 | Trial completion date: Dec 2024 ➔ Dec 2027 | Trial primary completion date: Dec 2023 ➔ Dec 2026

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • LY75

Oxford BioTherapeutics Initiates Phase Ib Clinical Trial for OBT076 in Patients with Advanced Solid Tumors by Dosing First (Bloomberg) - "'Initiating the European arm of this trial is an important milestone for our partnership with OBT and the development of balstilimab with OBT076 as a promising therapy for advanced solid tumors,' said Dr. Steven O'Day...'The combination of our proprietary anti-PD1 checkpoint inhibitor, balstilimab, with OBT's CD205 targeting ADC has the potential to deliver a powerful immunotherapeutic effect. We look forward to further exploring this novel immuno-oncology combination to advance treatment options for patients with chemo-refractory advanced cancers.'"

Media quote

Oxford BioTherapeutics Initiates Phase Ib Clinical Trial for OBT076 in Patients with Advanced Solid Tumors by Dosing First Patient in Combination with CPI Balstilimab in Europe (GlobeNewswire) - "Oxford BioTherapeutics...announced that it has initiated a Phase 1b combination trial evaluating its lead candidate, OBT076 - a CD205 targeting ADC - and Agenus’ proprietary anti-PD1 checkpoint inhibitor (CPI), balstilimab, in patients with advanced solid tumors by dosing its first patient at a European site. The study will be conducted at centres in France, Belgium, and Greece...This extension of OBT’s US Phase I Clinical Trial for OBT076 will evaluate the clinical efficacy of OBT076 in combination with balstilimab in patients with solid tumors including lung, gastric and ovarian cancer....OBT has also expanded its Phase 1b clinical trial investigating the safety, tolerability and pharmacokinetic profile of OBT076 as a monotherapy in Europe."

Trial status • Endometrial Cancer • Gastric Cancer • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

AdCC_2023-01: Study of OBT076 Associated or Not in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma of the Head and Neck (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Groupe Oncologie Radiotherapie Tete et Cou

IO biomarker • Metastases • New P1 trial • Adenoid Cystic Carcinoma • Head and Neck Cancer • Oncology

Combinations containing the anti-CD205 antibody drug conjugate MEN1309/OBT076 show strong pre-clinical activity in diffuse large B cell lymphomas (EORTC-NCI-AACR 2018) - P1; "The combinations with the PI3K-delta inhibitor idelalisib and the immunomodulant lenalidomide presented additivity in only one cell line. No benefit was seen combining MEN1309 with the proteasome inhibitor bortezomib.Conclusions.Very promising preclinical anti-lymphoma activity was observed with MEN1309 in combination with venetoclax, ibrutinib and especially rituximab, providing the bases for further clinical development of this novel ADC in a combinatorial setting. CT and EG: equally contributed."

Diffuse Large B Cell Lymphoma

Oxford BioTherapeutics announces Phase 1b trial in collaboration with GORTEC to investigate OBT076 in Adenoid Cystic Carcinoma (ACC) of the head and neck (GlobeNewswire) - "Oxford BioTherapeutics Ltd. (OBT)...announces it has entered into a collaboration with Groupe d'Oncologie Radiothérapie Tête Et Cou (GORTEC), an established, internationally renowned, European oncology and radiotherapy consortium specialising in clinical and laboratory research specifically for the benefit of head and neck cancer patients, to undertake a new Phase 1b trial investigating OBT’s lead asset, OBT076, in patients with Adenoid Cystic Carcinoma (ACC)."

Licensing / partnership • Adenoid Cystic Carcinoma • Oncology • Solid Tumor

CD205, a target antigen for a novel ADC: Evaluation of antigen expression on TNBC, pancreatic adenocarcinoma and bladder urothelial carcinoma. (ASCO 2019) - P1; "CD205 is heterogeneously expressed in the majority of TNBC and UC and in all PAC cases. The results of this study support the clinical investigation of MEN1309 in these tumor types."

The anti-CD205 antibody drug conjugate MEN1309/OBT076 shows synergistic activity in combination with the monoclonal antibody rituximab in diffuse large B cell lymphomas (AACR-NCI-EORTC 2022) - P1 | "The in vivo experiment based on a low dose of MEN1309 (1mg/Kg) showed an increased survival for animals treated with the combination M+R, in line with previously reported benefit using higher dose of MEN11309 (2.5mg/Kg). In immunoblotting analyses of xenografts samples, a downregulation of CD205 and CD20 was observed, especially after exposure to M+R, suggesting that the treatments might lead to degradation of their target receptors, perhaps due to ubiquitination as reported with anti-Her2 antibodies and with rituximab itself."

Combination therapy • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Achieving Favourable Clinical Outcomes With CPIs in PDL1 Low Patients by ‘Priming’ the Immune System with an ADC – A Case Study (ADC London 2023) - "• Discussing how ADCs have the potential to reengage the immune system to make more patients eligible for checkpoint inhibitor therapy • Outlining recent findings presented at AACR suggesting that combining ADC drug OBT076 with CPIs could achieve favourable clinical outcomes by ‘priming’ the immune system resulting in near complete responses, in two chemo-refractory advanced cancer patients with low PD-L1 expression after 2-5 cycles followed by 1-2 cycles of a checkpoint inhibitor"

Clinical • Clinical data • IO biomarker • Oncology • PD-L1

Potential novel Immuno-oncology mechanism revealed during translational phase I Immuno-blood profiling of experimental ADC medicine OBT076 in a gastric cancer patient (AACR 2022) - P1 | "Here we report on a potential novel immuno-oncology mechanism revealed during the Translational Phase I (NCT04064359) immuno-blood profiling of a chemo-refractory patient treated with OBT076, an experimental CD205-directed ADC.A chemo-refractory advanced gastric cancer patient with 60% CD205 expression in the primary tumor via IHC and having previously undergone 2 lines of chemotherapy treatment (Docetaxel/cisplatin/5FU and Ramucirumab/Paclitaxel), received five 21-day cycles of OBT076 (one at 2.5mg/kg and four cycles at 2.0 mg/kg) followed by 1 cycle of Pembrolizumab (PZ; 200mg) ~4 weeks later...These findings suggest that OBT076 activates the patient’s immune response against the tumor through a potentially novel mechanism: drug-induced depletion of CD8+ CD205+ immuno-suppressive cells and subsequent T-cell activation. Additionally, our data support the use of immune checkpoint inhibitors in conjunction with OBT076 to achieve favorable clinical outcomes."

Clinical • IO biomarker • P1 data • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • PD-1 • PTPRC

Phase 1 study of OBT076, a first-in-class anti-DEC205 ADC, in patients with advanced/metastatic solid tumors: Safety, efficacy, and PK/PD results. (ASCO 2022) - P1 | "OBT076 at 3.0mg/kg has shown favorable safety profile with manageable neutropenia. The preliminary efficacy has shown preliminary antitumoral single agent activity in gastric, ovarian and lung cancer. The two patients who received a sequential administration of pembrolizumab after OBT076 showed major tumor activity."

Clinical • IO biomarker • P1 data • PK/PD data • Gastric Cancer • Gastrointestinal Cancer • Hematological Disorders • Lung Cancer • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • PD-L1

Safety and Preliminary Efficacy of OBT076 in Recurrent/Metastatic CD205+ Solid Tumors (clinicaltrials.gov) - P1 | N=150 | Recruiting | Sponsor: Oxford BioTherapeutics Ltd | N=70 ➔ 150 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Enrollment change • Trial primary completion date • Oncology • Solid Tumor

Agenus Advances Portfolio with 6 Clinical Collaborations (GlobeNewswire) - "Targovax to conduct a clinical trial combining botensilimab and balstilimab with ONCOS-102...in patients with PD-1 relapsed/refractory melanoma; Oxford BioTherapeutics to conduct a clinical trial combining balstilimab with OBT076...in patients with solid tumors, including lung, gastric, and ovarian cancer; Immunogenesis to conduct a clinical trial combining balstilimab and zalifrelimab with evofosfamide...in patients with advanced solid tumors, including prostate, pancreatic, HPV-negative head and neck cancer; Targovax to conduct a clinical trial combining QS-21 STIMULON with TG01...in up to 3 cancer indications, including multiple myeloma; Rottapharm Biotech is conducting a clinical trial combining balstilimab with CR6086 (EP4 antagonist) in patients with pMMR-MSS colorectal cancer; Nelum is conducting a clinical trial combining zalifrelimab with NLM-001...and chemotherapy in patients with advanced pancreatic cancer."

Licensing / partnership • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Melanoma • Multiple Myeloma • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor

Oxford Bio collaborates with Agenus to support clinical development of OBT’s antibody drug conjugate OBT076 in combo with Agenus’ CPI balstilimab (Pharmabiz) - "'We look forward to collaborating with Oxford BioTherapeutics to bring this novel combination to patients,' said Steven O'Day....'The clinical data generated with OBT076 in advanced solid tumours is promising, and we believe will broaden the therapeutic benefit of balstilimab observed across treatment-resistant tumours."

Media quote

Oxford BioTherapeutics to Present Initial Positive Data from Phase I Trial at ASCO 2022 (PRNewswire) - P=1 | N= 70 | NCT04064359 | Sponsor: Oxford BioTherapeutics Ltd | "Oxford BioTherapeutics...today announced it will present preliminary clinical data from its ongoing Expansion Phase I Trial (NCT04064359) of its experimental CD205-directed ADC, OBT076, at the American Society of Clinical Oncology (ASCO) Annual Meeting 2022 being held 3-7 June in Chicago, IL....PK data showed that Cmax of 40.000-90.000 ng/ml was achieved between 2.5 and 3.5mg/kg. In Part 1, seven patients derived clinical benefit despite being in disease progression at trial entry of which one experienced major improvement with complete disappearance of ascites and metastatic adenopathy after cycle 3....'I look forward to the full analysis of the trial and further clinical development of OBT076 as a therapeutic for solid tumors where there is significant unmet need in these difficult to treat cancers'."

P1 data • Oncology • Solid Tumor

Oxford BioTherapeutics Announces Collaboration with Agenus to Support the Clinical Development of OBT's Antibody Drug Conjugate OBT076 in combination with Agenus' CPI Balstilimab (PRNewswire) - "Oxford BioTherapeutics...announced that it has entered into a collaboration and supply agreement with Agenus Inc...to support a clinical trial evaluating the combination of OBT076 with the anti-PD1 checkpoint inhibitor (CPI) balstilimab....OBT plans to evaluate the clinical efficacy of OBT076 in combination with Agenus proprietary CPI, balstilimab....Under the terms of the agreement, OBT will be the sponsor of the combination trial and responsible for operational execution, and Agenus will provide drug supply and scientific support....The study will be conducted in the US as well as in several European countries including France, Germany, Belgium and Greece, and will focus on patients with solid tumors including lung, gastric and ovarian cancer."

Licensing / partnership • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

OBT076, a clinical-stage ADC, displays synergy with oxaliplatin and cisplatin in preclinical gastric cancer models (AACR 2022) - "These results and those from ongoing in vivo studies in gastric cancer models will be discussed.In summary OBT076, a clinical stage ADC displays synergistic anti-tumor effects in preclinical gastric cancer models, when used in combination with Ox or Cis. OBT076 is currently being evaluated in the gastric clinical population where Platinum-based therapies remain the mainstay of treatment."

Preclinical • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor