Cisplatin plus gemcitabine for adults after PD‑1 therapy failure or with certain rare advanced tumors

Multi-cohort, Single-arm, Phase II Study of the Efficacy and Side Effects of Cisplatin Plus Gemcitabine in the Treatment of PD1 Failure or Intensive Treatment of Some Rare Tumors

This study will test whether the chemotherapy combination cisplatin plus gemcitabine can shrink advanced solid tumors in adults whose cancer progressed after PD‑1 therapy or who have certain rare aggressive tumors.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 84 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: Enfortumab, Sacituzumab, Disitamab, toripalimab, vedicitumumab, chemotherapy, immunotherapy, doxorubicin
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07046650 on ClinicalTrials.gov

What this trial studies

This is a multi‑cohort, single‑arm Phase II trial giving a cisplatin plus gemcitabine regimen to adults with advanced solid tumors, including patients whose disease progressed after PD‑1 therapy and selected rare tumor types. Patients must have measurable disease and adequate organ function and receive treatment at a single center in Shanghai. The trial measures tumor response and records side effects to determine activity and tolerability of the combination in these settings. Results will clarify whether a cisplatin‑based approach retains anti‑tumor activity after prior immunotherapy or in rare cancers lacking standard options.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed advanced solid tumors who have measurable disease, ECOG 0–1, adequate organ function, and prior PD‑1 therapy failure or one of the specified rare tumor types are the intended participants.

Not a fit: Patients with poor performance status (ECOG >1), inadequate blood, liver, or kidney function, no measurable lesions, or contraindications to cisplatin are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the regimen could provide an effective chemotherapy option to shrink tumors or control disease for patients after PD‑1 failure or with rare advanced tumors.

How similar studies have performed: Cisplatin‑based chemotherapy is an established effective treatment for urothelial and germ cell cancers, but using cisplatin plus gemcitabine specifically after PD‑1 failure or across varied rare tumors is less well studied.

Eligibility criteria

Inclusion Criteria:

* 1\. Written informed consent was obtained before enrollment. 2. Age ≥18 years old; 3. Patients with corresponding cancer confirmed by histological and/or cytological examination; 4. Consent to treatment; 5. ECOG score: 0-1; 6. Previous PD-1 therapy failure; 7. At least one measurable lesion (≥10 mm on CT scan for non-nodal lesions and ≥15 mm on CT scan for nodal lesions according to RECIST criteria).

  8\. Have adequate organ function: 9. Blood routine: Absolute Neutrophil Count (ANC) 1.5×109/L, Platelet (PLT) ≥70×109/L, Hemoglobin (HGB) ≥80g/L; 10. Liver function: serum Total Bilirubin (TBIL) ≤1.5× Upper Limit of Normal Value (ULN); Alanine Aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤3×ULN; Serum albumin ≥28 g/L; Alkaline Phosphatase (ALP) ≤5×ULN; Patients who met the above criteria after conventional liver-protective therapy and could be stable for at least 1 week could be enrolled after investigator's evaluation.

  11\. Renal function: creatinine clearance ≥60 mL/mi (using the standard Cockcroft-Gault formula) : 12. Coagulation: International Normalized Ratio (INR) ≤1.5 /PT≤1.5×ULN, aPTT≤1.5×ULN; If the subject is receiving anticoagulant therapy, as long as the PT and INR are within the prescribed range of anticoagulant drugs 13. Estimated survival time ≥3 months; 14. Contraception during treatment 15. Ability to adhere to study access schedules and other protocol requirements.

Exclusion Criteria:

* 1\. Poor patient compliance; 2. Prior exposure to cisplatin and/or gemcitabine and documented progression 3. With ≥ grade 2 myocardial ischemia or myocardial infarction, arrhythmia (QTc≥470ms), and ≥ grade 2 congestive heart failure (New York Heart Association \[NYHA\] classification); 4. Severe active or uncontrolled infection (≥CTCAE grade 2 infection) requiring systemic antibacterial, antifungal, or antiviral therapy, including pulmonary tuberculosis infection.

  5\. Active hepatitis (transaminase did not meet the inclusion criteria, hepatitis B reference: HBV DNA≥2000 IU/ml or ≥104 copies /ml; Hepatitis C reference: HCV RNA≥2000 IU/ml or ≥104 copies /ml; After nucleotide antiviral therapy, those below the above criteria can be enrolled). Chronic hepatitis B virus carriers with HBV DNA \< 104 IU/ml could only be enrolled if they received antiviral therapy at the same time during the trial.

  6\. A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 7. Severe nausea, headache, insomnia, fatigue, somnolence, dry mouth, dizziness and constipation; 8. Patients with a history of active tuberculosis; 9. Patients who underwent major surgical treatment, open biopsy, or significant traumatic injury within 28 days before the initiation of study treatment; Or have a wound or fracture that has not healed for a long time; 10. Currently participating or having participated in another clinical investigator within 4 weeks before study initiation 11. Patients with a history of severe allergies 12. Is at risk for bleeding, or has coagulopathy, or is receiving thrombolytic therapy 13. People who have a history of psychotropic drug abuse and cannot quit or have mental disorders 14. Subjects who, in the investigator's judgment, had a concomitant medical condition that seriously compromised the safety of the subjects or interfered with the completion of the study, or who were deemed to be ineligible for enrollment for any other reason. "There was a clear previous history of neurological and psychiatric disorders, such as dementia, epilepsy, or seizure prone episodes.

  15\. The presence of concomitant diseases (such as severe diabetes mellitus, thyroid disease, and psychosis), or serious and/or unstable medical, psychiatric, or other conditions (including laboratory abnormalities) that, in the judgment of the investigators, seriously compromise the safety of the subjects or prevent the subjects from completing the study, or the presence of serious and/or unstable medical, psychiatric, or other conditions (including laboratory abnormalities) that affect the safety of the patients or prevent the patients from providing informed consent, "Or the presence of any psychological, family, sociological, or geographic factors that affect the study protocol and follow-up plan.

  16\. The investigator did not consider it appropriate to participate in the trial for any reason

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Cancer Center, Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Sheng Zhang, PhD

Conditions Advanced Solid Tumors