On September 18, 2020 Oncologie, Inc., a precision medicine company using an innovative RNA-based biomarker platform to predict patient responses for potentially first-in-class targeted oncology therapies, announced new data and analyses from its lead clinical programs, bavituximab and navicixizumab (Press release, OncXerna Therapeutics, SEP 18, 2020, View Source [SID1234572120]). On the basis of these positive data, the company also announced its rebranding to OncXerna Therapeutics, Inc., a change that reinforces the company’s focus on using its RNA-based approach to guide novel, targeted treatments to specific people with cancer.

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"With a deep understanding of the tumor microenvironment biology at the RNA-level through our novel biomarker panel, we aim to dramatically improve clinical outcomes by matching patients to therapies with a mechanism of action that targets that specific biology," said Laura Benjamin, Ph.D., President and Chief Executive Officer at OncXerna Therapeutics. "Today’s results demonstrate a clear ability of our first panel to distinguish responders versus non-responders in our bavituximab and navicixizumab programs, and we are excited to deploy this approach in the next prospectively-defined trials that could support registration."

Interim results from Phase 2 (ONCG100) trial of bavituximab and KEYTRUDA

Trial design and background:

The Phase 2 (ONCG100) trial is a multicenter, open-label, single-arm global trial designed to assess the safety, tolerability, and antitumor activity of the investigational agent bavituximab, a chimeric monoclonal antibody that targets phosphatidylserine, in combination with KEYTRUDA, Merck’s anti-PD-1 therapy, in patients with advanced gastric and gastroesophageal cancer who have progressed on or after at least one prior standard therapy. Bavituximab previously demonstrated clinical activity in a post-hoc subset analysis in patients with non-small cell lung cancer (NSCLC) who were given a PD-1 inhibitor following bavituximab treatment, suggesting that a treatment combination of bavituximab and a PD-1 inhibitor could generate similar activity in a prospective clinical trial. In addition to measuring safety and antitumor activity in this trial, OncXerna is deploying its proprietary RNA biomarker platform (TME Panel-1) to identify patients based on their response to treatment and the dominant biology of their tumor microenvironment with the potential to dramatically improve outcomes in the next, prospectively designed trial.

Approximately 80 patients in the U.S., United Kingdom, South Korea and Taiwan are planned for enrollment in two separate groups of patients: Checkpoint inhibitor-naïve and checkpoint inhibitor-relapsed. The trial is continuing to enroll both groups with planned updates from all patients during the first half of 2021.

Interim results:

Interim results provided today, from the first 36 patients enrolled and with a post-baseline scan in the checkpoint inhibitor-naïve group, include the following:

Patient demographics: Mean age of 61 years (55% non-Asian/45% Asian) with approximately 70% and 30% of patients receiving their second-line and third-line of treatment, respectively. In terms of mutation status, known MSI-H patients were excluded (MSS included) and enrollment was PD-L1 agnostic, with 25% of patients PD-L1 negative.

Safety and tolerability: Bavituximab and KEYTRUDA treatments were well tolerated with 90% of treatment emergent adverse events considered Grade 1-3. Fourteen patients had at least one serious adverse event (SAE). All SAEs were reported as not related to bavituximab and KEYTRUDA except for pneumonitis in one patient that resolved and was considered related to the combination of bavituximab and KEYTRUDA.

Efficacy measures: Bavituximab and KEYTRUDA achieved an overall response rate (ORR) of 19% (7/36) in the evaluable population and 43% (3/7) in exploratory analyses of patients with a low neutrophil-to-lymphocyte (NLR) ratio (<4) and identified as biomarker positive using OncXerna’s TME Panel-1. In a clinical trial of KEYTRUDA that led to an accelerated approval in the third-line setting, the ORR was 13% with a 16% ORR in PD-L1 positive patients and a 9% ORR in MSS patients. Treatment with bavituximab and KEYTRUDA also generated a complete response in 20% (2/10) of patients who were PD-L1, CPS<1; a patient population where KEYTRUDA historically generates very low complete responses. In terms of response duration, all confirmed responders remain in the trial, with the longest responder approaching one-year of duration of response.

Next steps:

These data are being presented at the European Society for Molecular Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020 taking place September 19-21, 2020.

OncXerna plans to conduct additional clinical trials designed to prospectively enrich for TME Panel-1 biomarker positive patients, as well as to explore additional solid tumor types.

OncXerna biomarker analysis from Phase 1b trial evaluating navicixizumab in ovarian cancer

Previously announced data and background:

OncXerna’s navicixizumab is a bispecific antibody designed to inhibit both Delta-like ligand 4 (DLL4) in the Notch cancer stem cell pathway as well as vascular endothelial growth factor (VEGF). Interim data from a Phase 1b dose escalation and expansion trial of navicixizumab plus paclitaxel in 44 platinum-resistant ovarian cancer patients who had failed more than two prior therapies and/or received prior Avastin (bevacizumab) therapy were presented virtually at the 2020 Society of Gynecologic Oncology (SGO) Annual Meeting in May 2020. Treatment with navicixizumab and paclitaxel demonstrated an ORR of 43% in all patients, and 64% and 33% in bevacizumab-naïve, and bevacizumab pre-treated patients, respectively. Treatment-related adverse events were manageable and included hypertension (58%), headache (29%), fatigue (26%) and pulmonary hypertension (18%).

Updated biomarker analyses and results:

Using its RNA-based biomarker TME Panel-1, OncXerna recently analyzed patient tissue samples obtained from 28 of the 44 patients from the Phase 1b trial. Results from this analysis revealed the following:

Clinically meaningful improvement in median progression-free survival (PFS) of 9.2 months for TME Panel-1 biomarker positive patients (n=10) compared with a median PFS of 3.5 months for biomarker negative patients (n=13), hazard ratio (0.276). The confirmed ORR for TME Panel-1 biomarker positive patients (n=10) was 70% compared to 31% ORR for TME Panel-1 biomarker negative patients (n=13).

Patients in the TME Panel-1 biomarker positive panel achieved a 70% ORR, and excluded all who had progressive disease, compared with a 31% ORR for patients in the TME Panel-1 biomarker negative panel. In Avastin-experienced patients, achievement of a 71% ORR and 100% disease control rate (DCR) in TME Panel-1 biomarker positive patients (n=7) compared with 25% ORR and 50% DCR achieved in biomarker negative patients (n=8) (Table 1).

Table 1: TME Panel-1 Results from Phase 1b trial of Navicixizumab plus placlitaxel in patients with late-stage ovarian cancer

Avastin Naïve and Experienced
Confirmed Clinical Response (%) Biomarker positive (n=10) Biomarker negative (n=13)
ORR 70% 31%
DCR 100% 69%
CR 0% 8%
PR 70% 23%
SD 30% 39%
PD 0% 31%

Avastin Experienced
Confirmed Clinical Response (%) Biomarker positive (n=7) Biomarker negative (n=8)
ORR 71% 25%
DCR 100% 50%
PR 71% 25%
SD 29% 25%
PD 0% 50%
"Biomarker" refers to TME Panel-1

Next steps:

As a result of these analyses, OncXerna plans to conduct additional clinical trials designed to prospectively enrich for TME Panel-1 biomarker positive patients with ovarian cancer who are platinum-resistant and Avastin-experienced to support registration, as well as to explore additional solid tumor types.

About Bavituximab

Bavituximab is an investigational antibody that reverses immune suppression by inhibiting phosphatidylserine (PS) signaling and is currently in Phase 2 clinical trials to treat a specific subset of patients with advanced gastric cancer to improve their response to anti-PD-1 treatment. The mechanism of action of bavituximab is to block tumor immune suppression signaling from PS to multiple immune cell receptor families (e.g., TIMs and TAMs). The dominant biology targeted by bavituximab may be relevant for patients with many types of solid tumors whose immune systems are too suppressed to benefit from currently available immune oncology therapies. Our clinical trials currently combine bavituximab with KEYTRUDA to test the hypothesis that relieving immunosuppression can enhance responses to checkpoint inhibitors. Bavituximab is an investigational agent that has not been licensed or approved anywhere globally, and it has not been demonstrated to be safe or effective for any use, including for the treatment of advanced gastric cancer.

About Navicixizumab

Navicixizumab is an investigational anti-DLL4/VEGF bispecific antibody that has demonstrated antitumor activity in patients who have progressed on Avastin (bevacizumab) in a Phase 1a/b clinical trial. The U.S. Food and Drug Administration granted Fast Track designation to navicixizumab for the treatment of high-grade ovarian, primary peritoneal or fallopian tube cancer in patients who have received at least three prior therapies and/or prior treatment with Avastin. OncXerna is targeting patients whose dominant tumor biology is driven by angiogenesis with a focus beyond VEGF to include broader anti-angiogenic pathways. Navicixizumab is an investigational agent that has not been licensed or approved anywhere globally, and it has not been demonstrated to be safe or effective for any use, including for the treatment of advanced ovarian cancer.