HONOLULU – The novel antibody-drug conjugate tisotumab vedotin (TV) shows encouraging activity and tolerability in heavily pretreated recurrent or metastatic cervical cancer, according to findings from the phase 1/2a .
The investigator-assessed overall response rate (ORR) among 55 patients enrolled in the cervical cancer expansion portion of the study was 35%, and the confirmed response rate was 22%, including one complete response lasting 46 weeks,, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
The median duration of response in confirmed responders was 6 months, median progression-free survival (PFS) was 4.1 months, and 6-month PFS was 40%, said Dr. Hong, deputy chair, department of investigational cancer therapeutics, division of cancer medicine, the University of Texas MD Anderson Cancer Center, Houston.
“Overall, the independent review and investigator review were highly correlated,” he noted.
Study participants had recurrent or metastatic cervical cancer that progressed on standard therapy, and Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1. Most had received at least two prior therapies.
As established in the phase 1 dose-escalation portion of the study, TV in the expansion phase was given at a dose of 2 mg/kg every 3 weeks until disease progression, toxicity, or withdrawal.
Median follow-up was 3.5 months and the median number of doses received was four; the treatment had acceptable tolerability, Dr. Hong said, noting that no treatment-related deaths occurred, and only 13% of patients had a dose reduction caused by an adverse event (AE).
The most common AE occurring in more than 20% of patients was epistaxis; most cases were grade 1. AEs of special interest and possibly related to the TV mechanism of action included neuropathy, bleeding-related events, and ocular events.
While there were a few cases of vaginal bleeding, they were believed to be caused by underlying disease, he noted.
The ocular events noted early in phase 1 of the study included mainly dry eyes and conjunctivitis, but a plan to mitigate these events, which involved the use of steroid eye drops, cooling eye masks, and dose reductions, reduced their incidence.
There were no grade 4 or 5 adverse events related to the agent, he said, noting that most patients came off study because of disease progression.
The prognosis for recurrent or metastatic cervical cancer is very poor, with a 5-year survival rate of only about 17%, Dr. Hong said, adding that data on the overall response and survival after the first line of therapy are somewhat limited.
Pembrolizumab () received Food and Drug Administration approval based on second-line setting data from the showing a median ORR of just 14% and median PFS of just 2.1 months in programmed death-ligand 1–positive cervical cancer, he noted.
“Tissue factor (TF) is a protein expressed in cervical cancer, as well as ... a broad range of solid tumors. It is associated with high tumor stage, metastasis, and poor prognosis,” he explained. “TV is a first-in-class antibody-drug conjugate that’s a fully human monoclonal antibody targeting tissue factor.”
The drug, which has multiple mechanisms of action, is conjugated to the microtubule disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. Findings regarding its safety and tolerability in cervical cancer and a number of other tumors were published recently in.
Dr. Hong’s presentation focused on the cervical cancer cohort.
The median PFS in innovaTV 201 compares favorably with that for pembrolizumab and supports continued investigation of TV, he said, noting that phase 2 studies of TV alone and in combination with other agents for recurrent or metastatic cervical cancer, as well as for platinum-resistant ovarian cancer, are ongoing.
The innovaTV 201 trial is sponsored by Genmab A/S. Dr. Hong reported having no disclosures.
SOURCE: Hong DS et al. SGO 2019, .