Upifitamab Rilsodotin Fails to Meet ORR End Point in NaPi2b+ Platinum-Resistant Ovarian Cancer

The phase 1/2 UPLIFT trial (NCT03319628) evaluating the antibody-drug conjugate (ADC) upifitamab rilsodotin (XMT-1536) in patients with platinum-resistant ovarian cancer failed to meet its primary end point of investigator-assessed overall response rate (ORR) in the NaPi2b-positive population, according to an announcement from Mersana Therapeutics.¹

At the data cutoff of May 31, 2023, topline data showed that among the NaPi2b-positive population (n = 141), the investigator-assessed ORR was 15.6% (95% CI, 10.0%-22.7%), including a complete response (CR) rate of 1.4%. The median duration of response (DOR) was 7.4 months. The ORR per independent radiology review (IRR) assessment in this population was 16.3% (95% CI, 10.6%-23.5%) with a CR rate of 5.0% and a median DOR that was not reached.

In the total population (n = 268), the investigator- and IRR-assessed ORRs were both 13.1%. The CR rate was 1.1% per investigator assessment and 4.1% per IRR assessment. The median DOR was 7.4 months and 10.7 months per investigator and IRR assessments, respectively.

“We are deeply disappointed that UPLIFT’s efficacy failed to replicate previous data from approximately 100 patients in the dose-expansion portion of our phase 1b clinical trial,” Arvin Yang, MD, PhD, senior vice president and chief medical officer of Mersana Therapeutics, stated in a news release. “While the DOR was longer than that from the dose-expansion portion of upifitamab rilsodotin phase 1b clinical trial, the lower bound of the confidence interval for the primary end point did not meet our goal of excluding a 12% ORR seen with standard-of-care single-agent chemotherapy.”

Detailed efficacy and safety data will be presented in the future in an appropriate forum, according to Mersana.

“We are in the process of conducting an in-depth analysis of various factors to better understand the results as well as the characteristics of patients who responded to upifitamab rilsodotin therapy, particularly those whose responses were deep and durable,” Yang added. “We extend our deepest gratitude to all of the patients, family members, caregivers, and investigators who contributed to UPLIFT.”

UPLIFT was a single-arm trial that enrolled patients at least 18 years of age with a histological diagnosis of metastatic or recurrent high-grade serous ovarian cancer, including fallopian tube or primary peritoneal cancer, that was resistant to platinum-based chemotherapy.² One to 4 prior lines of systemic therapy were required, and prior treatment with bevacizumab (Avastin) was needed for patients who received 1 or 2 previous lines of therapy.

Key exclusion criteria included low-grade, clear cell, endometrioid, mucinous, carcinosarcoma, germ-cell, mixed histology, or stromal tumors; prior treatment with mirvetuximab soravtansine-gynx (Elahere) or another ADC containing an antitubulin payload; and primary platinum-resistant disease defined by a lack of response or progression within 3 months after completing frontline platinum-containing chemotherapy.

Enrolled patients received upifitamab rilsodotin once every 28 days until disease progression, unacceptable toxicity, or discontinuation based on the decision of the patient or physician.

NaPi2b positivity was defined as a tumor proportion score of at least 75%.1 Secondary end points included investigator-assessed ORR in the overall population, DOR, and safety/tolerability.

In the overall population, patients received a median of 3 prior lines of therapy, and 31% of patients received 4 prior lines of treatment. Specifically, 84% of patients received prior bevacizumab, and 69% of patients were previously given a PARP inhibitor.

Regarding safety, data from UPLIFT were generally consistent with prior findings for upifitamab rilsodotin.

References

1. Mersana Therapeutics announces topline data from UPLIFT clinical trial in patients with platinum-resistant ovarian cancer and strategic reprioritization. News release. Mersana Therapeutics. July 27, 2023. Accessed July 27, 2023. https://ir.mersana.com/news-releases/news-release-details/mersana-therapeutics-announces-topline-data-uplift-clinical
2. First-in-human study of XMT-1536 in cancers likely to express NaPi2b. ClinicalTrials.gov. Updated January 25, 2023. Accessed July 27, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03319628