Combining iparomlimab and tuvonralimab with chemotherapy and radiation for cervical cancer

Phase II, Single-Arm, Multicenter Clinical Study of Iparomlimab and Tuvonralimab in Combination With Paclitaxel Plus Cisplatin/Carboplatin and Radiotherapy for the Treatment of Locally Recurrent and Oligometastatic Cervical Cancer

This study is testing if combining two new drugs with chemotherapy and radiation can help people with locally recurrent cervical cancer live longer and feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Shandong Cancer Hospital and Institute (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone, iparomlimab, tuvonralimab
• Locations: 1 site (Jinan, Shandong Recruiting)
• Trial ID: NCT06942416 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of iparomlimab and tuvonralimab in combination with paclitaxel, cisplatin/carboplatin, and radiotherapy for patients with locally recurrent and oligometastatic cervical cancer. The study aims to determine if this combination therapy improves overall response rates, progression-free survival, disease control rates, and overall survival while also identifying predictive biomarkers for treatment efficacy. Participants will receive the treatment according to a specified protocol and will be monitored for various clinical outcomes and safety throughout the trial. Additionally, they will provide samples for biomarker exploration.

Who should consider this trial

Good fit: Ideal candidates are women aged 18-75 with histologically confirmed locally recurrent or oligometastatic cervical cancer after initial treatment.

Not a fit: Patients with extensive metastatic disease or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with recurrent and oligometastatic cervical cancer.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches in treating various cancers, indicating potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

1. Signed written informed consent prior to any trial-related procedures;
2. Female, aged ≥18 and ≤75 years;
3. ECOG PS 0-1;
4. Histologically or cytologically confirmed primary cervical cancer (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma) at initial diagnosis, meeting clinical diagnostic criteria;
5. Locally recurrent or oligometastatic cervical cancer after initial treatment. Total recurrent + metastatic lesions ≤5.Oligometastasis criteria:Lymph node metastases within the same region = 1 lesion;Liver metastases ≤1 lesion;Lung metastases ≤3 lesions
6. At least one measurable lesion (including primary lesion) suitable for radiotherapy and evaluable per RECIST v1.1;
7. Available tumor tissue sample for biomarker assessment;
8. Expected survival ≥6 months;
9. Normal organ function (within 7 days pre-enrollment):

(1) Hematological criteria (no transfusion/granulocyte/platelet-stimulating drugs within 14 days):

1. Hemoglobin (Hb) ≥80 g/L
2. Absolute neutrophil count (ANC) ≥1.5×10⁹/L
3. Platelets (PLT) ≥50×10⁹/L (2) No functional organic disease:

a) ALT/AST ≤2.5×ULN, total bilirubin ≤1.5×ULN, ALP ≤3×ULN, albumin ≥30 g/L b) Serum Cr ≤1.5×ULN (if \>1.5×ULN, CrCl ≥50 mL/min by Cockcroft-Gault formula) c) PT prolongation ≤6 sec, APTT ≤1.5×ULN d) TSH ≤ULN (if abnormal, FT3/FT4 must be normal) f) LVEF \>50% 10. Prior anti-tumor treatment toxicities recovered to ≤Grade 1 (CTCAE v5.0) pre-treatment, excluding:

* Alopecia/pigmentation (any grade)
* Peripheral neuropathy (≤Grade 2)
* Other toxicities where benefit-risk favors treatment 11. Non-sterilized/childbearing-potential females must:
* Use medical contraception (IUD/oral contraceptives/condoms) during treatment + 3 months post-treatment
* Negative serum/urine HCG within 7 days pre-enrollment
* Non-lactating 12. Expected compliance with protocol follow-up following criteria:

  1. Prior immunotherapy (e.g., immune checkpoint inhibitors);
  2. Pathological diagnosis of gastric-type adenocarcinoma;
  3. Active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism). Exceptions: vitiligo; childhood asthma fully resolved without intervention in adulthood. Exclusion: asthma requiring bronchodilator therapy;
  4. Current use of immunosuppressants or systemic/absorbable topical corticosteroids (equivalent to \>10 mg/day prednisone) for immunosuppression, continued within 2 weeks before enrollment;
  5. History of Grade 3-4 immune-related adverse events (irAEs) associated with prior anti-tumor immunotherapy;
  6. Poorly controlled cardiac conditions:

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  1. NYHA Class II or higher heart failure
  2. Unstable angina
  3. Myocardial infarction within 6 months
  4. Clinically significant supraventricular/ventricular arrhythmia requiring treatment
  5. QTc \>450 ms (males) or \>470 ms (females); 7. Coagulation abnormalities (INR \>1.5 or PT \>16 s), bleeding tendency, or current thrombolytic/anticoagulant therapy; 8. Prior radiotherapy/chemotherapy/hormonal therapy/surgery/targeted therapy completed \<4 weeks before study treatment (or \<5 drug half-lives, whichever is longer); unresolved toxicities (excluding alopecia) from prior therapies \>CTCAE Grade 1; 9. Poorly controlled third-space effusion requiring drainage before first trial drug administration; 10. Significant hemoptysis (≥2.5 mL/day) within 2 months before randomization; 11. Known hereditary/acquired bleeding/thrombotic disorders (e.g., hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism); 12. Active infection or unexplained fever \>38.5°C during screening/before first dose; 13. Objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonitis, or severe pulmonary dysfunction; 14. Immunodeficiency (e.g., HIV infection) or active hepatitis:

     * HBV DNA \> upper limit of normal (ULN)
     * HCV RNA \> ULN; 15. Use of other investigational drugs within 4 weeks before first dose; radiotherapy/local therapy within 2 weeks without full recovery; 16. Concurrent/prior malignancies (except cured basal cell carcinoma/cervical carcinoma in situ); 17. Planned concurrent systemic anti-tumor therapy during the study; 18. Live vaccination within 4 weeks before treatment or planned during the study; 19. Other conditions potentially requiring study termination per investigator judgment:
     * Severe comorbidities (including psychiatric disorders) requiring treatment
     * Critical lab abnormalities
     * Social/family factors compromising safety or data/sample collection.

Where this trial is running

Jinan, Shandong Recruiting

• Shandong Cancer Hospital Affiliated to Shandong First Medical University — Jinan, Shandong Recruiting, China (Recruiting)

Study contacts

• Principal investigator: Peng Xie — Shandong Cancer Hospital and Institute
• Study coordinator: Jing liu

Conditions Cervical Cancer; Neoplasm Recurrence, Local; Oligometastatic; Immunotherapy; Paclitaxel; Cisplatin; Carboplatin; Radiation Therapy