Following safety reports of bleeding events after treatment with upifitamab rilsodotin among patients with platinum-sensitive ovarian cancer, the FDA places a partial clinical hold on enrollment for the UP-NEXT and UPGRADE-A trials.
This article was originally published by Cancer Network®.
The FDA has placed a partial clinical hold on patient enrollment for the phase 3 UP-NEXT trial (NCT05329545) and the phase 1 UPGRADE-A trial (NCT04907968), both of which are evaluating upifitamab rilsodotin (XMT-1536) in patients with platinum-sensitive ovarian cancer, according to a press release from Mersana Therapeutics.
The regulatory agency paused enrollment after investigators submitted an aggregate safety report on bleeding events in patients receiving upifitamab rilsodotin. Across approximately 560 patients receiving treatment, the assessment highlighted 5 grade 5 bleeding events, the causes of which are under evaluation.
Developers anticipate receiving written correspondence from the FDA requesting a comprehensive evaluation of upifitamab rilsodotin safety data including the bleeding events. Additionally, the study investigators look to convene with the regulatory agency to lift the partial clinical hold and progress with patient enrollment in the UP-NEXT and UPGRADE-A trials.
The company also announced that it completed patient enrollment for the phase 1b/2 UPLIFT trial (NCT03319628) investigating upifitamab rilsodotin among patients with platinum-resistant ovarian cancer. Investigators expect to share topline data from this trial by early August and intend to submit these findings to the FDA once available.
“Patient safety is always at the forefront for us, and work is now underway to compile further analyses that may inform FDA,” Anna Protopapas, president and chief executive officer at Mersana Therapeutics, said in the press release. “Additionally, with UPLIFT top-line data on the near-term horizon, we will soon have a much more complete assessment of both the efficacy and safety profile for upifitamab rilsodotin in platinum-resistant ovarian cancer.”
Investigators of the multi-center phase 3 UP-NEXT trial are evaluating upifitamab rilsodotin as a treatment for patients with recurrent, platinum-sensitive high-grade serous ovarian cancer, including those with fallopian tube and primary peritoneal cancer, expressing high levels of NaPi2b. Patients will be randomly assigned to receive upifitamab rilsodotin or saline placebo once every 4 weeks until completion, disease progression, unacceptable toxicity, voluntary discontinuation, or death.
The primary end point is progression-free survival per RECIST v1.1 criteria. Secondary end points include overall survival, adverse effects, changes in ECOG performance status, objective response rate, and number of patients receiving concomitant treatments.
Patients 18 years and older with a histological diagnosis of high-grade serous ovarian cancer and platinum-sensitive recurrent disease are eligible to enroll on the UP-NEXT trial. Additional inclusion criteria include receiving 4 to 8 cycles of platinum-based chemotherapy and available tumor tissue block or slides for evaluating NaPi2b expression.
In the open-label, multi-center phase 1 UPGRADE-A trial, investigators are assessing upifitamab rilsodotin plus carboplatin among patients with high-grade serous ovarian cancer. In the dose escalation and dose expansion cohorts, patients will receive upifitamab rilsodotin on day 1 of each 28-day cycle in combination with carboplatin until disease progression or unacceptable toxicity.
The primary end points are the maximum tolerated dose (MTD) of upifitamab rilsodotin plus carboplatin and the feasibility of administering the regimen at MTD or the recommend phase 2 dose. Secondary end points include safety and tolerability, anti-neoplastic effects, and the association of NaPi2b tumor expression with objective tumor response.
Patients 18 years and older with a histological diagnosis of metastatic or recurrent high-grade serous ovarian cancer, including fallopian tube or primary peritoneal cancer, are eligible for enrollment on the UPGRADE-A trial. Additional eligibility criteria include receiving 1 to 3 prior lines of therapy, an ECOG performance status of 0 or 1, and measurable disease per RECIST v1.1 criteria.
Mersana Therapeutics announces partial clinical hold on UP-NEXT and UPGRADE-A clinical trials. News release. Mersana Therapeutics. June 15, 2023. Accessed June 16, 2023.