Ovarian clear cell carcinoma (OCCC), a rare and notoriously chemoresistant form of ovarian cancer, continues to confound clinicians with limited treatment options and poor outcomes. However, emerging research suggests a new combination immunotherapy strategy could offer hope—even for patients whose tumors lack molecular features known to predict immunotherapy benefit.
A late-breaking presentation at the annual meeting of the Society of Gynecological Cancer (SGO), held April 10-13, 2026, in San Juan, Puerto Rico, reported interim results from an open-label, single-arm phase 1b/2 trial (NCT06065462) investigating the combination of LB-100, a protein phosphatase 2A (PP2A) enzyme inhibitor, in combination with the anti-PD-1 checkpoint inhibitor dostarlimab (Jemperli®; GSK) in patients with platinum-resistant OCCC, specifically those with wild-type (non-mutated) PPP2R1A and proficient mismatch repair (pMMR).
Study Highlights:
- 21 patients enrolled; median age 60.5 (range 32–74), most with multiple prior therapies.
- At a 12-month median follow-up (range 1.4-22), the objective response rate (ORR) was 30%, and the disease control rate (DCR) was 40% (8/20, 95% CI 19.1-63.9%), with a median duration of response of 11.7 months.
- The median overall survival has not been reached, but the 6- and 12-month OS probabilities were promising: 84% (95% CI 0.64-0.94) at 6 months and 69% (95% CI 0.44-0.84) at 12 months.
- Safety profile was acceptable: 20% experienced grade 3+ side effects, most commonly liver enzyme elevation.
“This is the first trial to show a clinical efficacy signal in a pure ovarian, all pMMR population, expanding the potential benefit of immunotherapy beyond patients with known favorable tumor mutations,” said Helen Clark, MD, a fellow at the University of Texas MD Anderson Cancer Center in Houston, and co-author of the study.
The rationale for this approach builds on prior findings that OCCC tumors with PPP2R1A mutations respond better to immune checkpoint blockade, but these mutations are rare. By pharmacologically inhibiting PP2A with LB-100, researchers hope to extend immunotherapy benefits to the majority of OCCC patients with wild-type PPP2R1A.
Specifically, prior investigation reported markedly prolonged overall survival (OS) with ICB in patients with PPP2R1A-mutant OCCC (66.9 months versus 9.2 months for patients with wild-type tumors). This suggested that pharmacological PP2A inhibition with LB-100 may enhance the anti-tumor effect of the PD-1-blocking monoclonal antibody dostarlimab in patients with OCCC who lack genetic PP2A deficiency.
Based on promising results, a second cohort is enrolling to increase LB-100 exposure mid-cycle, potentially enhancing drug efficacy and better mimicking the biology observed in PPP2R1A-mutant cancers. If further benefit is confirmed, this would pave the way for a future randomized trial.
“OCCC is intrinsically platinum-resistant, making recurrent disease challenging to treat. Our findings suggest that combining LB-100 with dostarlimab may improve the sensitivity of checkpoint inhibition and offer a new, rational strategy for a population with limited options,” concluded Clark.
The trial, conducted by LIXTE Biotechnology, is part of ongoing efforts to identify effective, biomarker-driven therapies for difficult gynecologic cancers.
“The findings […] provide new hope for patients with ovarian cancer, a disease that thus far has limited therapeutic options,” said Bas van der Baan, LIXTE’s Chief Scientific Officer.
“[Our …] proprietary compound, LB-100, combined with GSK’s anti-PD1 drug dostarlimab, has shown an acceptable safety profile. All 21 planned participants in the trial have been enrolled, and 20 were evaluated for efficacy in this interim analysis. Based on those favorable results, an additional cohort of 21 patients with a higher exposure to LB-100 is in the process of enrolling,” van der Baan concluded.
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Clinical trial
Safety and Efficacy of Targeting PP2A in Ovarian Clear Cell Carcinoma Using Dostarlimab and LB-100 – ClinicalTrials.gov ID NCT06065462
Highlight of Prescribing Information
Dostarlimab (Jemperli®; GSK)[Prescribing Information]
Reference
[1] Clark H, Hinchcliff E, Al Anssari H, Dai Y, Fix S, Knisely A, Hong Leung C, Yuan Y, Wilke R, Westin S, Sood A, Jazaeri A. Combination PP2A inhibition and PD-1 blockade with LB-100 and dostarlimab in ovarian clear cell carcinoma. Gynecologic Oncology; Volume 208, Supplement, May 2026, Page S456. DOI: 10.1016/j.ygyno.2026.02.029
Featured image: Helen Clark, MD, a fellow at the University of Texas MD Anderson Cancer Center in Houston, and co-author of the study, presents the study results during the SGO 2026 Annual Meeting on Women’s Cancer. © 2026 SGO. Used with permission.
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