FDA approves Tisotumab Vedotin-tftv for patients with recurrent or metastatic cervical cancer
Tisotumab vedotin (Tivdak) has received fast-track approval from the FDA for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression during or after chemotherapy.1
The regulatory decision is based on data from the innovaTV 204 phase 2 trial (NCT03438396), in which the antibody-drug conjugate elicited an objective response rate (ORR) of 24% (95% CI, 15.9 % to 33.3%) by independent review committee. using the RECIST v1.1 criteria in patients with recurrent or metastatic cervical cancer who have previously received dual chemotherapy and bevacizumab (Avastin).2
Of those who responded to treatment, 7% had a complete response and 17% had a partial response. The median duration of response with tisotumab vedotin was 8.3 months (95% CI, 4.2 – not achieved). The median time to response (TTR) with ADC was 1.4 months (range, 1.1 to 5.1) and activity was noted during the first 2 cycles of treatment.
“Once recurrent or metastatic cervical cancer progresses, more options are needed for these patients,” said Robert L. Coleman, MD, scientific director, US Oncology Research and principal investigator of the trial. innovaTV 204 clinic, said in a press release. “This is an important development for patients with recurrent or metastatic cervical cancer. “
The innova TV 204 single-arm, multicenter, phase 2 trial included a total of 101 previously treated patients with recurrent and / or metastatic cervical cancer who received intravenous tisotumab vedotin at a dose of 2.0 mg / kg every 3 weeks until disease progression or unacceptable toxicity.
To be eligible for enrollment, patients must have recurrent or extrapelvic metastatic disease, have experienced disease progression during or after doublet chemotherapy with bevacizumab (if eligible), have received 2 or less prior systemic treatments, and have an index of ECOG performance from 0 to 1.
The primary endpoint of the trial was ORR according to RECIST v1.1 and the Independent Imaging Review Committee (IRC) assessment. Secondary endpoints included ORR by investigator assessment and RECIST criteria, overall survival (OS), and safety.
DOR, TTR, and progression-free survival (PFS) by CRI and investigator served as additional endpoints. The researchers also assessed the biomarkers and health-related quality of life with the treatment.
The median age of study participants was 50 years, 95% were Caucasian, and 58% had an ECOG performance index of 0. Additionally, 68% of patients had squamous cell carcinoma, 27% had adenocarcinoma, and 5% adenosquamous carcinoma. Almost all of the patients, 94%, had extrapelvic metastatic disease at baseline.
Fifty-four percent of participants had previously received cisplatin plus radiation therapy and 70% had received 1 prior line of systemic treatment for recurrent or metastatic disease. In addition, 63% of patients had previously received bevacizumab and dual chemotherapy as first-line therapy and 56% did not respond to their last received systemic therapy.
Patients received treatment for a median of 4.2 months with a median of 6 doses; a high dose intensity of 95.9% has been reported with the agent. Four patients continued to receive treatment; 65% of patients discontinued due to radiographic progression. Thirteen percent of patients discontinued treatment due to toxicities, 8% due to clinical progression, 5% due to withdrawal of consent, 4% due to death, and 1% by investigator decision.
Additional data presented at the ESMO 2020 Virtual Congress demonstrated that 4% of those who received ADC achieved disease stability while 24% experienced disease progression by CRF. Seventy-nine percent of the participants also experienced a reduction in target lesions.
In particular, clinically significant responses were observed regardless of tumor histology, previous treatment lines, responses to prior systemic treatment and whether or not first-line chemotherapy was administered to bevacizumab / doublet. Responses were also observed regardless of the level of membrane TF expression.
The median reported PFS with ADC was 4.2 months, while OS was 12.1 months. The 6-month PFS rate was 30%, while the OS rate at this stage was 79%.
The ADC had a manageable security profile. The agent’s prescribing information includes a boxed warning for ocular toxicity, as well as a warning for peripheral neuropathy, hemorrhage, pneumonitis, and embryo-fetal toxicity.
The most common side effects reported with tisotumab vedotin included decreased hemoglobin (52%), fatigue (50%), decreased lymphocytes (42%), nausea (41%), peripheral neuropathy ( 39%), alopecia (39%), epistaxis (39%), conjunctival adverse effects (37%), hemorrhage (32%), decrease in leukocytes (30%), increase in creatinine (29%), dryness ocular (29%), increase in international normalized prothrombin ratio (26%), prolongation of activated partial thromboplastin time (26%), diarrhea (25%) and rash (25%).
“[Tisotumab vedotin’s] approval for monotherapy in the United States is an important step for women with recurrent or metastatic cervical cancer with disease progression during or after chemotherapy, as they need a new option process and we look forward to making it available to them, ”Jan van de Winkel, PhD, CEO of Genmab, said in a press release. “The journey towards the approval of [tisotumab vedotin] started almost 20 years ago with innovative research by scientists at Genmab and Seagen and reflects on our goal to make an impact on the lives of cancer patients and their families. Today’s announcement marks Genmab’s evolution into a fully integrated biotechnology company and we would like to thank patients, caregivers, researchers and our collaborators for their participation in our clinical studies.
1. Seagen and Genmab announce fast-track FDA approval for TIVDAK (tisotumab vedotin-tftv) for the treatment of previously treated recurrent or metastatic cervical cancer. Press release. Seagen Inc. and Genmab A / S. September 20, 2021. Accessed September 20, 2021. https://bit.ly/3lJOwAI
2. Coleman RL, Lorusso D, Gennigens C, et al. Tisotumab vedotin in previously treated recurrent or metastatic cervical cancer: results of the innovaTV 204 / GOG-3023 / ENGOT-cx6 phase 2 study. Ann Oncol. 2020; 31 (suppl 4): S1162-S1163. doi: 10.1016 / j.annonc.2020.08.2262