A Phase II/III Trial to Evaluate the Efficacy and Safety of QL1706 in Patients With Nasopharyngeal Carcinoma

• Status: Recruiting
• Trial end date: 2024-12-30
• Target enrollment: 0
• Participant gender: All

Summary

This is a randomized, open, multicenter phase II/III trial to compare the efficacy and safety of QL1706 and carrilizumab combined with gemcitabine and cisplatin in first-line treatment of recurrent or metastatic nasopharyngeal carcinoma.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Qilu Pharmaceutical Co., Ltd.
• Treatments: Cisplatin; Gemcitabine

Criteria

Inclusion Criteria:

1. The subject will participate voluntarily and sign the informed consent form.

2. Age ≥ 18 years when signing the informed consent form, male or female.

3. The Eastern Collaborative Oncology Group (ECOG) physical status score was 0 or 1.

4. Expected survival ≥ 3 months.

5. Patients with pathologically confirmed nasopharyngeal carcinoma.

6. Patients with primary diagnosis of metastatic nasopharyngeal carcinoma [stage IVb according to the American Joint Committee on Cancer AJCC staging system (8th edition)] or patients with recurrent (including recurrent or metastatic) nasopharyngeal carcinoma who are not candidates for radical surgery or radiotherapy or other local treatment; and for recurrent or metastatic lesions must be untreated systemically: previously treated with neoadjuvant chemotherapy with curative intent, Patients with adjuvant chemotherapy, radiotherapy or radiotherapy must have had ≥ 6 months between the last chemotherapy and or radiotherapy and the time of disease recurrence and/or development of metastases.

7. Patients have at least one imaging measurable lesion according to RECISTv1.1 evaluation criteria; for lesions that have received prior radiotherapy or other local treatment there must be evidence of definite progression of the lesion after the end of local treatment in order to be selected as a measurable lesion.

8. Subjects may provide eligible archived (within 2 years, up to a maximum of 5 years if approved) or freshly obtained tumor tissue, approximately ≥ 15 unstained FFPE pathology sections (minimum of ≥ 10 if approved).

9. Adequate organ function prior to first use of the experimental drug (no blood components, leukocyte-raising drugs, or platelet-raising drugs are allowed within 7 days prior to obtaining laboratory tests)

1. Absolute neutrophil count ≥ 1.5 x 109/L.

2. Platelet count ≥ 100×109/L.

3. Hemoglobin ≥ 90 g/L.

4. Serum albumin ≥ 28 g/L.

5. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (CLcr) calculated by Cockcroft-Gault formula ≥ 50 mL/min.

6. Total bilirubin ≤ 1.5 × ULN (<3 × ULN in patients with Gilbert syndrome)

7. AST and ALT ≤ 2.5×ULN (≤ 5×ULN allowed in the presence of liver metastases)

8. International normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤ 1.5 x ULN (screening is allowed for patients on stable doses of anticoagulant therapy such as low molecular heparin or warfarin and with an INR within the expected therapeutic range of anticoagulants.

9. Cardiac left ventricular ejection fraction (LVEF) >50%.

10. Subjects (both female and male) agree to use effective contraception from the time they sign the informed consent until 180 days after the last use of the trial drug. Women who are not pregnant or breastfeeding from the time they sign informed consent until 180 days after the last use of the trial drug.

Exclusion Criteria:

1. Presence of symptomatic central nervous system (CNS) metastases, soft meningeal metastases, or spinal cord compression due to metastases.

2. Prior systemic anticancer treatment with approved drugs or trial drugs.

3. End date of palliative radiotherapy targeting bone metastases or soft tissue, etc. ≤ 7 days from imaging of baseline tumor lesions

4. Presence of carcinomatous meningitis prior to first study treatment

5. Active autoimmune disease present within 2 years prior to the first administration of the investigational drug and requiring systemic systemic therapy. Subjects with relevant alternative therapy who are stable are allowed to be included.

6. Disease requiring systemic treatment with corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive drugs present within 2 weeks prior to first study treatment.

7. At the investigator's discretion, have a serious concomitant condition that jeopardizes patient safety, or interferes with patient completion of the study, such as hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg) not controlled by two or more antihypertensive medications, or severe diabetes mellitus.

8. Exclude subjects with any of the following cardiovascular diseases

1. Acute myocardial infarction, with New York Heart Association class III or IV heart failure that occurred within 6 months prior to the first study treatment.

2. Poorly controlled cardiovascular disease, including angina pectoris, pulmonary hypertension, or severe cardiac rhythm or conduction abnormalities, prior to first study treatment.

3. Mean 12-lead ECG showing a QT interval (QTcF) >450ms (men) or >470ms (women) prior to first study treatment.

9. Persons with previous or current interstitial lung disease, pneumoconiosis, radiation pneumonia, or severely impaired lung function that in the judgment of the investigator may interfere with the monitoring and management of suspected drug-related pulmonary toxicity.

10. Prior to first study treatment with clinically uncontrollable third interstitial fluid, such as pleural effusion, peritoneal effusion, or pericardial effusion that cannot be controlled by drainage or other means and who, in the judgment of the investigator, cannot be enrolled.

11. Prior immunotherapy, including immune checkpoint inhibitory antibodies (e.g., anti-PD-1, PD-L1, CTLA-4 antibodies, etc.), immune checkpoint agonist antibodies (e.g., anti-ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), and immune cell therapy, etc.

12. Underwent surgery within 4 weeks prior to first study treatment and did not recover

13. History of allogeneic hematopoietic stem cell transplantation or history of organ transplantation (except corneal transplantation)

14. Presence of systemic infection or other serious infection requiring intravenous antibiotics for >7 days within 14 days prior to the first study treatment.

15. HIV positive patients; syphilis spiral antibody positive individuals; hepatitis B surface antigen (HBsAg) positive individuals with hepatitis B virus deoxyribonucleic acid (HBVDNA) ≥ 2000 IU/ml or 104 copies/ml; HCV antibody positive individuals with HCV RNA positive individuals.

16. Those who are known to have received antituberculosis treatment within one year prior to their first study treatment.

17. Have received a live vaccine within 4 weeks prior to first study treatment, except that inactivated vaccine is allowed to be planned for use during study treatment.

18. Patients with a known history of psychotropic substance abuse, alcohol or drug abuse; a clear previous history of neurological or psychiatric disorders, including epilepsy or dementia

19. Patients with a history of other malignancies (except cured basal cell skin cancer, cervical carcinoma in situ, papillary thyroid cancer, etc.) within 5 years prior to first study treatment.

20. Patients with known prior hypersensitivity to macromolecular protein agents, or to QL1706 and Carrilizumab monoclonal antibody and any component thereof, or to gemcitabine or cisplatin and any component of their excipients.

21. Those who have participated in other clinical studies and used other clinical trial drugs within 4 weeks prior to first study treatment.

22. Have received a proprietary Chinese medicine with an antitumor indication within 2 weeks prior to first study treatment.

23. Patients who, in the judgment of the investigator, may increase the risk associated with the study, may interfere with the interpretation of the study results, or who, in the opinion of the investigator and/or sponsor, are not suitable for enrollment.