FDA Approves sBLA for Tisotumab Vedotin in Cervical Cancer

Gynecologic cancer, cervical cancer: © tom - stock.adobe.com

• Tisotumab vedotin-tftv (Tivdak) is an antibody-drug conjugate being evaluated for the treatment of patients with recurrent or metastatic cervical cancer in the phase 3 innovaTV 301 trial (NCT04697628).
• Tisotumab was granted accelerated approval for the treatment of metastatic cervical cancer in September 2021.
• This supplemental biologics license application (sBLA) seeks to convert the accelerated approval to a full approval.

The FDA accepted the sBLA to convert the accelerated approval of tisotumab vedotin to full approval for patients with recurrent or metastatic cervical cancer whose disease has progressed on or after first-line therapy. The application has also received priority review and has a Prescription Drug User Fee Act target action date of May 9, 2024.¹

The approval is based on findings from the phase 3 innovaTV 301 trial, the findings of which were presented at the 2023 European Society of Medical Oncology Congress. Tisotumab demonstrated a 30% reduction in the risk of death compared with investigator’s choice of chemotherapy when used in the second or third line in the intent-to-treat population.

At a median follow-up of 10.8 months (95% CI, 10.3-11.6), the median overall survival (OS) was 11.5 months (95% CI, 9.8-14.9) with tisotumab vs 9.5 months (95% CI, 7.9-10.7) with chemotherapy (HR, 0.70, 95% CI, 0.54-0.89; P = .0038). The 12-month OS rates were 48.7% and 35.3% with tisotumab and chemotherapy, respectively.²

The median progression-free survival (PFS) was 4.2 months (95% CI, 4.0-4.4) with tisotumab vs 2.9 months (95% CI, 2.6-3.1) with chemotherapy (HR, 0.67; 95% CI, 0.54-0.82; P <.0001). The 6-month PFS rates were 30.4% and 18.9% with tisotumab and chemotherapy, respectively.

“The phase 3 innovaTV 301 trial demonstrated a favorable benefit/risk profile, including improvement in overall survival, and adds to the overall data supporting [tisotumab] as a treatment option for people with recurrent and metastatic cervical cancer who have limited treatment options,” said Roger Dansey, MD, chief development officer of oncology at Pfizer, in a press release.¹ “The FDA acceptance of our sBLA for review is important progress toward continuing to offer an option that can extend the lives of more adults with cervical cancer.”

Enrollment in the phase 3 innovaTV 301 trial was open to patients who received a diagnosis of recurrent or metastatic cervical cancer, had documented disease progression on or after doublet chemotherapy with or without bevacizumab (Avastin) and an anti–PD(L)1 agent if eligible and available, measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and exposure to no more than 2 prior lines of therapy.²

The study randomized patients 1:1 to receive 2.0 mg/kg of intravenous tisotumab vedotin every 3 weeks (n = 253) or investigator’s choice of chemotherapy (n = 249), which could have included topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. The primary end point was OS with secondary end points of PFS, ORR, and safety.

“Ultimately, in all cancer care, the word ‘cure’ is something that we don't hear. But if we can get a way to cure some of our patients…if we move forward, we may have that opportunity,” Brian Slomovitz, MD, gynecologic oncologist, director of gynecologic oncology, Mount Sinai Medical Center, Miami Beach, Florida, and primary investigator of the innovaTV 301 trial, said in an interview with Targeted Oncology^TM. “But we're seeing that with immunotherapy and in endometrial cancers, we're seeing the word ‘cure.’ We saw that with PARP inhibitors and in BRCA-mutated ovarian cancers, where a percentage of patients are cured.”

“If we could get to a point with recurrent or metastatic cervical cancer, if we can get a portion of those patients cured, it'd be unprecedented,” Slomovitz added.

REFERENCES:

1. Tivdak supplemental biologics license application accepted for priority review by FDA for patients with recurrent or metastatic cervical cancer. News release. Pfizer. January 9, 2024. Accessed January 9, 2024. http://tinyurl.com/mud6nb9n

2. Vergote IB, Gonzalez Martin A, Fujiwara K, et al. innovaTV 301/ENGOT-cx12/GOG-3057: A global, randomized, open-label, phase III study of tisotumab vedotin vs investigator’s choice of chemotherapy in 2L or 3L recurrent or metastatic cervical cancer. Ann Oncol. 2023;34(suppl 2):S1276-S1277. doi:10.1016/j.annonc.2023.10.029