The UPGRADE-A trial assessing the combination of upifitamab rilsodotin and carboplatin in patients with platinum-sensitive high-grade serous ovarian cancer has initiated the dose-expansion portion of the study.
Trial Name: Upifitamab Rilsodotin (Xmt-1536) An Open-Label, Multicenter, Dose Escalation And Expansion Study Of Upifitamab Rilsodotin In Combination With Carboplatin In Participants With High Grade Serous Ovarian Cancer (Upgrade-A)
ClinicalTrials.gov Identifier: NCT04907968
Sponsor: Mersana Therapeutics
Recruitment Contact: Cassandra Carrington, 617-715-8214, medicalinformation@mersana.com
Completion Date: March 2025
The expansion portion of the UPGRADE-A clinical trial (NCT04907968) of upifitamab rilsodotin (XMT-1536; UpRi) in combination with carboplatin in platinum-sensitive ovarian cancer has begun dosing patients, according to Mersana Therapeutics, Inc.1
UpRi is a first-in-class NaPi2b-targeting antibody drug conjugate that has a novel scaffold-linker-payload. The treatment works to enable a high drug-to-antibody ratio and controlled bystander effect.
“Interim data from a previous phase 1b study of heavily pretreated patients with high-grade serous ovarian cancer reported clinical activity, most notably in patients with NaPi2b positive tumors [tumor proportion score ≥ 75], and a tolerable safety profile, without the severe peripheral neuropathy, neutropenia and ocular toxicity often seen with other antibody drug conjugates,” Theresa L. Werner, MD, senior director of clinical research, professor of medicine, oncology division, adjunct professor of obstetrics and gynecology, Huntsman Cancer Institute, University of Utah, told Targeted OncologyTM. “UPGRADE-A is a phase 1 dose-escalation and -expansion study to evaluate UpRi and carboplatin in recurrent platinum-sensitive high-grade serous ovarian cancer followed by UpRi maintenance. The dose-escalation portion of UPGRADE-A has completed enrollment, and the expansion portion is ongoing.”
In the open-label, non-randomized, phase 1 UPGRADE-A trial, the combination of UpRi and carboplatin is being investigated in patients with platinum-sensitive high-grade serous ovarian cancer after 1-3 prior lines of treatment.2
The trial will enroll approximately 48 patients aged 18 years and older with a histological diagnosis of metastatic or recurrent high-grade serous ovarian cancer, including fallopian tube, or primary peritoneal cancer. Patients are administered the combination every 4 weeks for 6 cycles followed by UpRi as a single-agent maintenance therapy.
Once the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is achieved in the dose-escalation portion of the study, a new group of patients will be administered UpRi at this fixed-dose in addition to carboplatin.
For enrollment in the study, patients must have received 1-3 prior lines of therapy, have an ECOG performance status of 0 or 1, provide a tumor sample, have adequate organ function within 14 days prior to enrollment, and have cardiac left ventricular ejection fraction ≥50% or ≥ the institution's lower limit of normal as measured by either Echo or MUGA scan. Additionally, all patients must have recovered from their toxicities from prior therapy or surgical procedures to ≤ grade 1.
Investigators are assessing the primary end points of maximum tolerated dose and feasibility of the combination of UpRi and carboplatin. Secondary end points of the trial include to assess the safety and tolerability, pharmacokinetics, overall response rate, duration of response, disease control rate, progression-free survival, and overall survival.
In the escalation portion of the study, the combination of carboplatin and UpRi was investigated at doses up to 36 mg/m2. Findings revealed that there were no dose-limiting toxicities at this dose level. The ongoing phase 3 UP-NEXT trial (NCT05329545) is evaluating UpRi at a dose of 30mg/m2, which is also the dose chosen for the expansion portion of UPGRADE-A.
“Results from the phase 2 UPLIFT study in patients with platinum resistant ovarian cancer are expected mid 2023. Based on these emerging single-agent safety and efficacy data, it is hypothesized that UpRi in combination with carboplatin may provide additional clinical benefit and an option for patients in earlier lines of treatment. UpRi is also being evaluated in the UP-NEXT phase 3 study evaluating UpRi monotherapy as post-platinum maintenance therapy in recurrent platinum-sensitive ovarian cancer,” concluded Werner.
