A Phase 3 Study of Manganese-primed Immunochemotherapy in Patients With Advanced Ovarian Cancer

NCT07822646 | Recruiting Phase 3 DMC

• 1 other identifier: CHN-PLAGH-BT-101
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 6

Brief Summary

Epithelial ovarian cancer is the most lethal gynecologic malignancy, and most patients eventually relapse and develop resistance to available therapies. Immune checkpoint inhibitors have shown limited overall efficacy in recurrent ovarian cancer, partly because of its immunosuppressive tumor microenvironment. Manganese (Mn2+) can activate the cGAS-STING pathway and may enhance antitumor immunity and the therapeutic effects of PD-1 blockade combined with chemotherapy. Following encouraging findings from an early-phase study, a randomized, single-blind, placebo-controlled phase II trial showed that the addition of manganese chloride to anti-PD-1 antibody, nab-paclitaxel, and cisplatin improved clinical outcomes compared with placebo, with an overall manageable safety profile. Based on these findings, this phase III trial is designed to confirm the efficacy and further evaluate the safety of Mn2+-primed immunochemotherapy in patients with advanced ovarian cancer.

Conditions

Ovarian Cancer

Keywords

Relapsed; Refractory; anti-PD-1 antibody; Manganese; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS time was measured from study entry to the first documentation of disease progression or death. Disease progression was determined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  12 months

Secondary Outcomes (3)

• Overall survival (OS)

  24 months

• Object response rate (ORR)

  24 months

• Number of Subjects with treatment-related adverse events (AEs)

  12 months

Other Outcomes (1)

• Number of participants with laboratory test abnormalities

  12 months

Study Arms (2)

Manganese primed anti-PD-1 plus nPP chemotherapy

EXPERIMENTAL

Subject received Manganese primed anti-PD-1 antibody, nab-paclitaxel and platinum chemotherapy every 3 weeks until achieving a second assessable complete response or progressive disease, development of unacceptable toxicity, or withdrawal of consent.

Drug: Manganese Chloride; Drug: Nab-paclitaxel; Drug: Platinum chemotherapy; Drug: Anti-PD-1 antibody

anti-PD-1 plus nPP chemotherapy

PLACEBO COMPARATOR

Subject received placebo, anti-PD-1 antibody, nab-paclitaxel and platinum chemotherapy every 3 weeks until achieving a second assessable complete response or progressive disease, development of unacceptable toxicity, or withdrawal of consent.

Drug: Nab-paclitaxel; Drug: Platinum chemotherapy; Drug: Anti-PD-1 antibody; Drug: Placebo

Interventions

Manganese Chloride DRUG

Administered by inhalation at 0.4mg/kg twice per week in the first 3-week cycle, and then inhaled 0.4mg/kg twice in the first week of each 3-week cycle thereafter

Manganese primed anti-PD-1 plus nPP chemotherapy

Nab-paclitaxel DRUG

Administered intravenously, 180-220mg/m2 on day 2 in a 3-week cycle (day 1 without Manganese priming)

Manganese primed anti-PD-1 plus nPP chemotherapy; anti-PD-1 plus nPP chemotherapy

Platinum chemotherapy DRUG

Administered intravenously, Cisplatin (60-80mg/m2) or Carboplatin (area under the curve \[AUC\] 4-6 mg/ mL per min) on day 2 in a 3-week cycle (day 1 without Manganese priming)

Manganese primed anti-PD-1 plus nPP chemotherapy; anti-PD-1 plus nPP chemotherapy

Anti-PD-1 antibody DRUG

Administered intravenously, 200mg on day 3 in a 3-week cycle (day 2 without Manganese priming)

Manganese primed anti-PD-1 plus nPP chemotherapy; anti-PD-1 plus nPP chemotherapy

Placebo DRUG

Administered by inhalation twice per week in the first 3-week cycle, and then inhaled twice in the first week of each 3-week cycle thereafter

anti-PD-1 plus nPP chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically or cytologically confirmed epithelial ovarian cancer, primary fallopian tube cancer, or peritoneal cancer.
• Patients who have received at least two prior lines of systemic therapy, including at least one platinum-based regimen.
• Patients who experienced disease progression during or within 6 months after completion of the most recent line of systemic therapy.
• Note: This most recent therapy is not required to be platinum-based and may be any systemic treatment (chemotherapy, targeted therapy, or other anticancer therapy).
• Patients with at least one measurable lesion.
• Patients who have received immunotherapy (anti-PD-1 antibodies, anti-PD-L1 antibodies), or bevacizumab, are not restricted from enrollment.
• Expected survival of more than 6 months.
• Age over 18 years.
• Patient weight \> 40 kg.
• ECOG performance status ≤ 2.
• Peripheral blood white blood cell count \> 3.5×10 /L.
• Bone marrow reserve and liver and kidney function (the following laboratory tests should be performed before initial treatment to prove):
• Absolute neutrophil count (ANC) ≥ 1,000/mm ;
• Hemoglobin \> 80 g/dL;
• Platelet count \> 80,000/mm ;

You may not qualify if:

• Absolute neutrophil count (ANC) \< 1×10 /L or platelets \< 80×10 /L or hemoglobin \< 80 g/dL (according to the normal values of the clinical trial center）.
• Serum total bilirubin levels higher than 3 times the upper limit of the reference range.
• ALT, AST, or ALP levels higher than 3 times the upper limit of the reference range when there are no liver metastases; ALT, AST, or ALP levels higher than 5 times the upper limit of the reference range when there are liver metastases.
• Patients receiving known strong inhibitors (e.g., ketoconazole) or inducers (e.g., rifampicin or St. John's Wort) of CYP3A4, or strong inhibitors (e.g., gemfibrozil) or inducers of CYP2C8; patients receiving treatment with potent P-gp inhibitors or inducers, or patients who cannot stop treatment with these agents for 2 weeks before the start of the study.
• Subjects' bowel obstruction or requirement for bowel obstruction-related interventions within 3 weeks prior to first study drug administration; subjects with incomplete bowel obstruction who have returned to normal within 1 month before the first dose of the experimental drug can be included in the study after discussion by the researchers.
• Patients with severe or uncontrolled ascites, defined as either of the following: a) symptomatic ascites corresponding to CTCAE ≥ Grade 2; b) history of therapeutic paracentesis for ascites within 3 weeks prior to enrollment.
• Organ failure:
• Heart: Grade III or IV.
• Liver: Grade C according to Child-Pugh B liver function classification.
• Kidney: Renal failure and uremia.
• Lung: Severe respiratory failure symptoms.
• Brain: Consciousness disorders.
• T-cell tumors such as T-cell lymphoma or T-cell leukemia.
• Major surgery within 4 weeks before enrollment, or planned major surgery during the study (excluding diagnostic surgery).
• HIV antibody positive, or other acquired, congenital immunodeficiency diseases, or patients with a history of organ transplantation.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (6)

Department of Obstetrics and Gynecology, Seventh Medical Center, Chinese PLA General Hospital

Beijing, Beijing Municipality, 100007, China

RECRUITING

Department of Bio-therapeutic, First Medical Center, Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

Department of Obstetrics and Gynecology, First Medical Center, Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

Peking University International Hospital

Beijing, Beijing Municipality, 102206, China

NOT YET RECRUITING

Department of Obstetrics and Gynecology, North China University of Science and Technology Affiliated Hospital

Tangshan, Hebei, 063000, China

NOT YET RECRUITING

Department of Gynecologic Oncology, Shanxi Province Cancer Hospital

Taiyuan, Shanxi, 030013, China

NOT YET RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Recurrence

Interventions

manganese chloride; 130-nm albumin-bound paclitaxel; spartalizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Weidong Han

CONTACT

+86-01066937463; hanwdrsw@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 11, 2026
• First Posted: September 16, 2026
• Study Start (Estimated): October 12, 2026
• Primary Completion (Estimated): April 12, 2029
• Study Completion (Estimated): December 20, 2030
• Last Updated: September 16, 2026

Record last verified: 2026-09

Locations

CN (6)