KEY TAKEAWAYS
- The phase 2 trial aimed to investigate the efficacy of MIRV in combination with pembrolizumab in improving the response to ICI in patients with MSS or pMMR EC.
- The primary endpoints were to determine ORR and PFS.
- Researchers noticed that the combination of MIRV and pembrolizumab shows promise in FRα-positive recurrent MSS/pMMR serous EC patients; further investigation is ongoing.
Folate receptor-alpha (FRα) expression correlates with poor prognosis in endometrial cancer (EC). Mirvetuximab soravtansine (MIRV), an antibody-drug conjugate (ADC) targeting FRα, demonstrated efficacy in Phase 1 trials in FRα-positive advanced/recurrent EC. MIRV’s mechanisms include target-mediated cytotoxicity and activation of monocytes, enhancing phagocytosis of tumor cells through Fc-FcγR interactions.
R. L. Porter and her team conducted a study by hypothesizing the MIRV’s potential to augment immune checkpoint inhibitors (ICI) response in microsatellite stable (MSS)/proficient mismatch repair (pMMR) EC, prompting a phase 2 investigation of MIRV plus pembrolizumab in recurrent/persistent EC.
They performed an inclusive analysis on patients with advanced or recurrent MSS/pMMR, FRα-positive (defined as ≥50% of tumor cells with ≥2+ staining on IHC by Ventana, Inc.) serous EC. Patients received MIRV 6 mg/kg AIBW and pembrolizumab 200 mg every 21 days until disease progression or unacceptable toxicity, with 1-3 prior lines of therapy allowed, including prior ICI therapy.
The co-primary endpoints were objective response rate (ORR) by RECIST 1.1 and the frequency of patients surviving progression-free for 6 months (PFS6). Sixteen patients were enrolled in Stage 1, with an additional 19 patients enrolled in Stage 2 if ≥2 objective responses or ≥2 PFS6 responses were observed. The combination would proceed further if 4 objective responses or 8 PFS6 events were achieved.
About 130 patient tumors were prescreened for FRα expression, revealing a median FRα of 30% (IQR: 5-55), with 43 (33.1%) classified as FRα positive (PS 2+ ≥50%). As of November 2023, 16 patients received study treatment, with a median follow-up of 4.7 months (IQR 2.9, 17.3). Among them, 6 patients (37.5%, 95% CI: 15.2-64.6%) achieved an objective response, including 1 confirmed complete response (CR) and 5 partial responses (PR) [3 confirmed (18.8%) and 2 unconfirmed (12.5%)]. Additionally, 31.3% (5/16) had stable disease, and 2 patients remained alive and PFS6.
The most common treatment-related adverse events (TRAEs) included AST elevation (50%), blurred vision (44%), fatigue (44%), and diarrhea (43%), with grade 3 TRAEs occurring in 2 patients (12.5%). Ocular toxicities of any grade were reported in 56.3% of patients. Updated efficacy and safety data and ongoing correlative studies will be presented at the meeting.
The study concluded that the combination of MIRV and pembrolizumab met the co-primary endpoint, indicating its potential for further investigation in FRα-positive recurrent MSS/pMMR serous EC. Ongoing investigations are focusing on identifying subpopulations most likely to benefit clinically from this combination therapy.
The trial was sponsored by the Dana-Farber Cancer Institute.
Source: https://www.abstractsonline.com/pp8/#!/20272/presentation/11425
Clinical Trial: https://clinicaltrials.gov/study/NCT03835819
Porter R. L., Xiong N., Tayob N., et al. (2024). “A phase 2, two-stage study of mirvetuximab soravtansine (IMGN853) in combination with pembrolizumab in patients with microsatellite stable (MSS) recurrent or persistent endometrial cancer.” Presented at AACR 2024 (Abstract CT008).
