Strata Oncology Inc. has inked an agreement with newcomer Elevation Oncology to ramp up patient identification and enrollment for the latter’s phase II CRESTONE study evaluating the use of seribantumab in patients with recurrent, locally advanced or metastatic solid tumors of any origin that have a neuregulin-1 (NRG1) gene fusion.

“NRG1 fusions are rare oncogenic drivers present across several tumor types, like lung and pancreatic, and patients with these cancers are often treated in community oncology centers making efficient use of limited tissue samples critical,” explained Dan Rhodes, CEO of Ann Arbor, Mich.-based Strata. “Through system-wide delivery of StrataNGS, our tumor molecular profiling test optimized for small tissue samples, we believe our nationwide network of health systems will help drive identification and enrollment of patients into this important study.”

Seribantumab

Seribantumab is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3. CRESTONE will aim to build on prior clinical experience from more than 800 patients demonstrating consistent safety and tolerability.

Elevation obtained seribantumab last year. “Merrimack Pharmaceuticals originally developed seribantumab for a broad population of patients in combination with other anti-cancer agents,” Shawn Leland, founder and chief business officer of Elevation, told BioWorld. The goal of the buy was to pursue a clinical development path in solid tumors driven by NRG1 gene fusions as a monotherapy.

“Patients whose tumors harbor an NRG1 gene fusion do not normally respond well to treatment with standard of care, including checkpoint inhibitors,” he explained. “NRG1 fusions have also been associated with lower OS [overall survival] and DFS [disease-free survival] and may also be a driving cause of resistance to previous targeted therapies. Tailored treatments are needed for these patients.”

Leland also noted that NRG1 is the predominant ligand of HER3. “[T]here is growing research in support of the therapeutic importance of inhibiting HER3 in patients whose tumors have an NRG1 fusion. With seribantumab’s ability to block HER3 ligand-dependent activation, HER3-HER2 dimerization, and in turn downstream signaling through the PI3K-AKT and MAPK pathways, we believe that therapeutic intervention with monotherapy seribantumab may provide an important option for patients whose tumors harbor an NRG1 fusion.”

Teaming up with Strata

Against that backdrop, Elevation is looking to team up with others. “We’ve been in touch with some of the founding team of Elevation for a little while now,” Strata’s Rhodes told BioWorld when asked how the partnership came about. “I think some of the Elevation investors were involved in other companies that have worked with Strata before.” That has helped to form the basis of a great relationship, he added.

His company has been running a next-generation sequencing (NGS) study known as the Strata trial that is operating at almost 30 health systems in the U.S. The goal is to standardize NGS testing for advanced cancer patients and developing a path from test results to enrollment to a partnered precision trial. “We’ve been operating this protocol now for several years,” he explained. “We’ve tested more than 30,000 patients and continue to grow.”

The company recently saw the presentation of data from the Strata trial at the 2020 Annual Meeting of the American Society of Clinical Oncology showing an expanded proportion of patients with actionable biomarkers due to the performance of StrataNGS on small tissue samples. The results demonstrated that less than half of >20,000 formalin-fixed paraffin-embedded tumor tissue samples met tumor surface area requirements for commercial hybrid-capture-based comprehensive genomic profiling (CGP) tests. StrataNGS, a PCR-CGP test, successfully reported results in 96% of all samples received.

Helping its collaboration with Elevation is the fact that Strata already has identified NRG1 gene fusion patients who could be eligible for this study. “But we’ll continue to identify more patients with this profile over time,” Rhodes added. In addition, the company will look back into its database to characterize NRG1 gene fusion-positive patients. It will investigate their treatment history data and work with investigators and network health systems to assess potential eligibility for Elevation’s study.

Looking ahead, Strata expects to announce additional pharma partnerships in the coming weeks. “I think it’s exciting to see that new targeted therapies, immunotherapies continue to be developed in this precision oncology framework: tumor-agnostic biomarker-guided trials.”

The company also has a study that it has completed and is preparing for publication in which it characterizes its experience sequencing more than 30,000 advanced tumors, specifically their performance of its testing in this setting.

He also hinted at initiatives around broadening the off-label use of approved therapies in precision indications. Additional information will be made available later in the year.

Emerging from stealth mode

For its part, Elevation, of New York, has made a splash with a $32.5 million series A financing in its debut. The financing was led by Aisling Capital and a syndicate of investors including Vertex Ventures HC, Qiming Venture Partners USA, Driehaus Capital Management, and BVF Partners.

At the same time, it reported not only the Strata partnership, but also tie ups with Ashion Analytics and Tempus to explore models for real-time identification, patient referral and enrollment of patients with tumors driven by rare genomic alterations. Rhodes confirmed that those partnerships are separate.

Elevation’s Leland told BioWorld that the company was making its debut in conjunction with the launch of its phase II study. "We hope that in addition to raising awareness about our company and CRESTONE, attention can also be drawn to the value of broad genomic testing and the importance of developing targeted therapies against actionable oncogenic drivers to bring therapeutic opportunities to all patients with advanced cancers.”

When asked how his company was able to attract the attention of partners so quickly, Leland noted that a big challenge in tackling a rare, genetically defined population like NRG1 fusions would be patient identification, particularly because NRG1 fusions represent 0.2% of solid tumors. The team reached out to companies focusing on genetic testing and NGS to form alliances for this purpose, and the results have been very positive.

“Between our partnerships with diagnostic companies like Ashion Analytics, Caris Life Sciences, Strata Oncology and Tempus, we are exploring a number of different collaboration models for proactively identifying patients with NRG1 fusions and evaluating their eligibility for treatment with seribantumab,” he continued. “An important aspect of several of these collaborations is the ability to utilize their vast networks of clinical trial sites to enable patient enrollment through a “just-in-time” site initiation system. Through this model, patients can go onto seribantumab in 14 days or less once an NRG1 fusion has been identified, and at their local oncology center.”

He stressed that the collaborations aim to supplement and enhance the company’s traditional clinical trial enrollment models. “We continue to partner with major academic institutions like Sarah Cannon Research Institute (SCRI) and other academic sites to be announced to ensure proper study conduct for CRESTONE. “

Looking ahead, the company is placing an emphasis on creating partnerships and working with diagnostic, clinical and advocacy groups to back patient identification for the current study and promote awareness about the value of genomic testing.

“CRESTONE and seribantumab are just the beginning,” he continued. “Elevation is positioned to identify and license/acquire other precision oncology products to supplement the current pipeline and leverage the core infrastructure that Elevation has put in place to further grow the company and expand precision therapeutic options for patients in need.”

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