FDA Grants Fast Track Status to Seribantumab for Solid Tumors Harboring NRG1 Gene Fusions

The FDA has granted a fast track designation to seribantumab for the tumor-agnostic treatment of advanced solid tumors that harbor NRG1 gene fusions.¹

The HER3-targeted monoclonal antibody inhibits the signaling initiated by the NRG1 fusion protein that directs a cancer cell to grow and proliferate.² Preclinical data have demonstrated that the agent prevented the activation of HER3 signaling in cells harboring an NRG1 gene fusion and destabilized the ERBB family signaling pathway, which included the activation of HER2, EGFR, and HER4.

Seribantumab is now under investigation in patients with advanced solid tumors with NRG1 fusions who have progressed following 1 or more previous lines of therapy, as part of the open-label, international, multicenter, phase 2 CRESTONE trial (NCT04383210).

“There are currently no approved therapies that specifically target NRG1 fusions, and therefore, receipt of fast track designation in a tumor-agnostic setting is a significant step in addressing this unmet need,” Shawn M. Leland, PharmD, RPh, founder and chief executive officer of Elevation Oncology, stated in a press release. “NRG1 fusions are a type of genomic alteration that causes unregulated cell growth and proliferation in a variety of solid tumors, and we look forward to working closely with the FDA as we continue exploring the potential of seribantumab to improve outcomes for patients whose tumor harbors this unique oncogenic driver.”

Patients with NRG1 fusion–positive tumors who were at least 18 years of age, had an ECOG performance status of 0 to 2, had at least 1 measurable extra-cranial lesion, and who had received a minimum of 1 prior standard treatment were eligible for enrollment to CRESTONE.^3,4

Those with a life expectancy of less than 3 months, who had symptomatic or untreated brain metastases, received another investigational agent or anticancer therapy within 28 days before seribantumab initiation, or another active malignancy that required systemic therapy, were excluded.

The trial is comprised of the following 3 cohorts:

• Pivotal Cohort 1 will include a minimum of 55 adult patients with solid tumors harboring NRG1 gene fusions who had previously received standard therapy except for ERBB-targeted treatment.
• Exploratory Cohort 2 will enroll up to 10 adult patients with solid tumors harboring NRG1 gene fusions who have previously received standard treatment, including ERBB-directed therapy.
• Exploratory Cohort 3 will include up to 10 adult patients with advanced solid tumors harboring NRG1 gene fusions that lack an EGF-like domain and who have previously received standard treatment, which could have included ERBB-directed therapy.

Study participants received seribantumab at a weekly intravenous dose of 3 g, administered over the course of 1 hour.

The primary outcome measure in the intention-to-treat population is objective response rate per RECIST v1.1 criteria by independent central radiologic review. Key secondary end points include duration of response, progression-free survival, overall survival, clinical benefit rate, and safety.

Initial data from CRESTONE will be shared via an oral presentation delivered during the 2022 ASCO Annual Meeting in June 2022.

To date, seribantumab has been given to more than 800 patients spanning twelve phase 1 and 2 clinical trials, as a single agent and in combination with other anticancer agents.

References

1. Elevation Oncology announces FDA fast track designation granted to seribantumab for the tumor-agnostic treatment of solid tumors harboring NRG1 gene fusions. News release. Elevation Oncology. May 25, 2022. Accessed May 25, 2022. https://prn.to/3LLAkSH
2. CRESTONE: clinical study of response to seribantumab in tumors with Neuregulin-1 (NRG1) fusions. Elevation Oncology website. Accessed May 25, 2022. https://bit.ly/3sXslLz
3. Study of seribantumab in adult patients with NRG1 gene fusion positive advanced solid tumors. ClinicalTrials.gov. Updated April 19, 2022. Accessed May 25, 2022. https://www.clinicaltrials.gov/ct2/show/NCT04383210
4. Bendell JC, Lim K-H, Burkard ME, et al. CRESTONE: Clinical study of response to seribantumab in tumors with neuregulin-1 (NRG1) fusions – a phase II study of the anti-HER3 mAb for advanced or metastatic solid tumors (NCT04383210). J Clin Oncol. 2021;39(suppl 3):TPS449. doi:10.1200/JCO.2021.39.3_suppl.TPS449