OPB-101 CAR T therapy for platinum-resistant ovarian cancer.

A Phase 1a/b Study to Evaluate the Safety and Efficacy of OPB-101, an Autologous Mesothelin (MSLN) CAR T Cell Therapy With Antigen-dependent Expression of OUTSMART™ Designed IL-2 Cytokine in Platinum-resistant Ovarian Cancer

This trial will test a one-time, personalized CAR T cell treatment (OPB-101) to see if it is safe and may help people with platinum-resistant ovarian cancer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Outpace Bio, Inc. (Industry-sponsored)
• Drugs / interventions: CAR T, chemotherapy
• Locations: 4 sites (Detroit, Michigan and 3 other locations)
• Trial ID: NCT07030907 on ClinicalTrials.gov

What this trial studies

This phase 1a/b dose-finding study gives participants their own T cells engineered to target mesothelin and to express an antigen-dependent IL-2 system (OUTSMART™), called OPB-101. After leukapheresis and manufacturing, participants receive a single hospitalized infusion and are closely monitored at the clinic frequently during the first months for safety and early signs of response. The trial uses escalating doses to identify the optimal and tolerable dose level. Key eligibility includes high-grade serous ovarian, peritoneal, or fallopian tube cancer that recurred within six months of platinum therapy, measurable disease, and adequate organ function.

Who should consider this trial

Good fit: Adults with histologically confirmed high-grade serous ovarian, peritoneal, or fallopian tube cancer that recurred within six months of platinum therapy who have had at least two prior systemic lines, measurable disease, ECOG 0–1, and adequate organ function are the intended candidates.

Not a fit: Patients with poor performance status, inadequate organ function, active infections, or tumors unlikely to express mesothelin may not benefit or be eligible for this therapy.

Why it matters

Potential benefit: If successful, OPB-101 could offer a new targeted option that controls tumors in patients whose ovarian cancer no longer responds to platinum chemotherapy.

How similar studies have performed: Mesothelin-targeted CAR T cells and engineered cytokine-expressing CARs have shown early safety and occasional tumor responses in phase 1 trials, but CAR T success in solid tumors remains limited and this specific OUTSMART™ IL-2 design is a novel approach.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years of age at the time of signing the informed consent form.
2. Histologically confirmed diagnosis of high grade serous epithelial ovarian, peritoneal, or fallopian tube cancer based on local histopathological findings.
3. Recurrent platinum-resistant disease defined as: Disease that has recurred within 6 months of the last receipt of platinum-based therapy.
4. Received at least 2 prior lines of systemic chemotherapy including a platinum-based chemotherapy.
5. Received prior therapy with a PARP inhibitor if the subject has a known germline or somatic BRCA1/2 mutation.
6. Measurable disease.
7. Consent to provide archived tumor tissue sample.
8. ECOG performance status of 0 or 1.
9. Adequate organ function.
10. Alkaline phosphatase ≤ 2.5 x ULN
11. ≤ Grade 1 dyspnea and oxygen saturation levels (SpO2) \> 92% on room air.
12. LVEF ≥ 50%
13. Life expectancy of ≥ 3 months
14. Adequate venous access.
15. Negative screen for infectious disease markers.
16. Negative serum pregnancy test.
17. Abstain from heterosexual activity or to use 2 forms of effective methods of contraception.

Note: Other protocol defined inclusion criteria could apply

Exclusion Criteria:

1. Women of child-bearing potential who are pregnant or breastfeeding.
2. Uncontrolled bacterial, fungal, or viral infections.
3. Active infection requiring systemic therapy.
4. Bleeding or thrombotic disorders or at risk for severe hemorrhage.
5. Any form of primary immunodeficiency.
6. Had an allogenic tissue/solid organ transplant.
7. Active autoimmune disease.
8. Concurrent treatment with systemic high dose corticosteroids.
9. Unresolved acute effects of any prior therapy.
10. Active invasive cancer other than the cancer under study.
11. Significant lung disease.
12. Clinically significant pericardial effusion.
13. Prior radiotherapy within 2 weeks of start of study intervention.
14. No major surgery within 28 days prior to enrollment.
15. Received investigational agents or tumor vaccines.
16. Received chemotherapy within the previous 3 weeks.
17. History of grade ≥ 3 ascites.
18. Active CNS involvement.
19. Received a live vaccine within 30 days prior to study treatment.
20. Received prior CAR T cell therapy.
21. Received prior mesothelin targeted therapy.
22. Dependent on intravenous hydration or total parenteral nutrition. Note: Other protocol defined exclusion criteria could apply

Where this trial is running

Detroit, Michigan and 3 other locations

• Karmanos Cancer Institute — Detroit, Michigan, United States (Recruiting)
• University of Minnesota — Minneapolis, Minnesota, United States (Recruiting)
• Roswell Park — Buffalo, New York, United States (Recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Study coordinator: John Ferraro, MBA

Conditions Ovarian Cancer Recurrent; Ovarian Cancer; Platinum Resistant Ovarian Cancer; Outpace; Ovarian cancer; Advanced ovarian cancer; cell therapy; CAR T