On April 7, 2022 Oxford BioTherapeutics (OBT), a clinical stage oncology company with a pipeline of immuno-oncology and Antibody Drug Conjugate (ADC)-based therapies, reported a forthcoming presentation featuring preliminary clinical data from its ongoing Expansion Phase I Trial (NCT04064359) of its experimental CD205-directed ADC, OBT076, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, taking place 8th – 13th April in New Orleans, US (Press release, Oxford BioTherapeutics, APR 7, 2022, View Source [SID1234611619]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The presentation highlights are below:

Near complete responses in two chemo-refractory advanced cancer patients with low PD-L1 expression after 2-5 cycles of OBT076 and 1-2 cycles of a CPI indicate preliminary signs of clinical activity, and
Translational work on patients receiving OBT076, followed by an immune CPI, whose immuno- blood profiling revealed a potential novel immuno-oncology mechanism for immune system reactivation and tumor shrinkage.
"We are pleased to share these data showing promising preliminary signs of clinical activity and a favorable tolerability profile for our experimental CD205-directed ADC, OBT076, in patients with advanced and chemo-refractory cancers," said Christian Rohlff, PhD, Chief Executive Officer (CEO) of Oxford BioTherapeutics. "The results support our excitement around OBT076 as a therapeutic capable of harnessing the immune system to treat patients with advanced, difficult to treat cancers both as monotherapy and in combination with a CPI. Our preliminary data suggest that depletion of CD205+ immuno-suppressive cells and subsequent T-cell activation after OBT076 treatment followed by a single cycle of a CPI coincides with the rapid resolution of the primary tumor, as well as metastases in a chemo-refractory advanced gastric cancer patient."

Summary of the Data to Be Presented at AACR (Free AACR Whitepaper)

The objective of the translational work emerging from the ongoing Phase I OBT076 trial (NCT04064359), presented at AACR (Free AACR Whitepaper), is to evaluate the antitumor activity of OBT076, at a lower test dose of 2.0-2.5 mg/kg, in combination with a CPI in chemo-refractory solid tumor patients.

As of the data cut-off (January 31, 2022), 2 patients with advanced solid tumors with at least 1 metastatic site had been treated with the combination. Patient 1 received OBT076 for 5 cycles; the first cycle at 2.5 mg/kg and subsequent cycles at 2.0 mg/kg, followed by 1 cycle of a CPI at 200 mg approximately 2 weeks later. Clinical response was evaluated and immunological markers (CD45, CD205, CD4, CD8, and PD1) in peripheral blood cells were quantified using flow cytometry.

Patient 1 had a diagnosis of chemo-refractory advanced gastric cancer with 60% CD205 expression in the primary tumor and had previously undergone 2 lines of conventional chemotherapy treatment. After 3 OBT076 cycles at 2.0 mg/kg, there was a ~40% shrinkage in the primary gastric tumor size and resolution of ascites and lymph node metastases.

Following 2 further cycles of OBT076 and 1 cycle of CPI, complete response was achieved for the primary tumor. Flow cytometry showed simultaneously occurring increases in PD1+ T-cells, T-cell induction, and decreases in immuno-suppressive CD4+ CD205+ and CD8+ CD205+ cells; coinciding with rapid resolution of the primary tumor, lymph node metastases and ascites.

Similar findings were reported for Patient 2 after 2 cycles with OBT076 followed by CPI. Both Patients 1 and 2 had near complete response after treatment with OBT076 followed by 1-2 cycles with CPI despite having low PD-L1 expression.

"These findings suggest that OBT076 may activate 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," said Rahim Fandi, MD, PhD, Chief Medical Officer (CMO) of Oxford BioTherapeutics. "The treatment of patients who are resistant to therapy with CPIs is challenging. These data give us hope that OBT076 could achieve favorable clinical outcomes in such patients when used in combination with immune CPIs. Based on these encouraging results, we are advancing OBT076 into the next stage of clinical development as both a single agent and in combination with a CPI, for the treatment of multiple solid tumor indications, with the goal of improving outcomes for patients with difficult-to-treat cancers."

The e-poster and abstract will be accessible on the AACR (Free AACR Whitepaper) conference website. The abstract and presentation details are as follows:

Title: Potential Novel Immuno-oncology Mechanism revealed during Translational Phase I Immuno- blood Profiling of Experimental ADC medicine OBT076 in A Gastric Cancer Patient.

Session: Immune Response to Therapies / Immune Monitoring and Clinical Correlates

Date: 11th April 2022 13:30:00 PM

Location: Poster Section 31
Poster #: 5497

Authors: Christian Rohlff et al.

OBT076 Further Clinical Development Plans

Based on these preliminary results, OBT plans to advance OBT076 as a monotherapy as well as in combination in trials in both checkpoint-naïve and resistant patients. These Phase 1b trials will assess the safety of OBT076 in combination with CPI in patients with solid tumors, and as a monotherapy in patients with solid tumors. Subsequent disease-specific Phase 2a trials are planned in patients with non-small cell lung cancer, ovarian cancer and gastric cancer. OBT is also planning for later-stage trials of OBT076, including in combination with CPI.