Recurrent or Metastatic Nasopharyngeal Cancer, Patients Who Have Experienced Treatment Failure at Least Second-line Chemotherapy
Conditions
Brief summary
This study is a randomized, open-label, multicenter Phase II clinical study, with the objective to assess the efficacy and safety of JMT101 Injection combined with Mitoxantrone Hydrochloride Liposome Injection in patients with recurrent/metastatic nasopharyngeal cancer who have failed at least two prior lines of treatment.
Detailed description
Participants will be screened within 28 days prior to treatment, and those who meet the inclusion criteria and do not meet any of the exclusion criteria will be enrolled in this study. Enrolled participants will be randomly assigned in a 1:1:1 ratio to the following treatment groups, with each group planned to include 30-50 participants: Mitoxantrone hydrochloride liposome will be administered for up to 6-8 cycles. After 6 cycles of administration, the investigator will decide whether to continue administration up to 8 cycles based on the patient's benefit-risk situation. JMT101 and the investigator-selected single-agent chemotherapy regimen will continue to be administered until progressive disease (PD) as assessed by the investigator according to RECIST v1.1 criteria, intolerable toxicity, withdrawal of informed consent by the subject, initiation of new anti-tumor treatment, loss to follow-up, death, or the end of the study, whichever occurs first.
Interventions
DRUGMitoxantrone Hydrochloride Liposome
Mitoxantrone Hydrochloride Liposome Injection 20mg/m2, or 16mg/m2, intravenous drip, Q4W.
DRUGJMT101 injection
JMT101 Injection 6 mg/kg, intravenous drip,
DRUGCapecitabine
The dosage of capecitabine is 1000 mg/m2, taken orally twice daily, administered on D1-14 (Days 1-14) of each cycle, with every 3 weeks as one cycle (Q3W);
DRUGDocetaxel injection
The dosage of docetaxel is 75 mg/m2, administered via intravenous drip on D1 of each cycle, Q3W.
DRUGGemcitabine hydrochloride for injection
The dosage of gemcitabine is 1000 mg/m2, administered via intravenous drip on D1 and D8 (Day 1 and Day 8) of each cycle, Q3W;
Sponsors
Shanghai JMT-Bio Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized, open-label, positive-controlled Phase II
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Able to understand and voluntarily sign the written ICF; 2. Aged 18-75 years old (inclusive), male or female; 3. Patients with nasopharyngeal cancer who have experienced treatment failure after prior PD-(L)-1 inhibitor therapy and at least second-line chemotherapy (including at least one line containing platinum); 4. According to RECIST v1.1, there is at least one measurable lesion, and the lesion has not previously undergone radiotherapy or has shown definite progression after radiotherapy; 5. ECOG PS score of 0-1; 6. Estimated lifespan of at least 3 months; 7. Have adequate organ function, laboratory test meets the following criteria (has not received transfusion or hematopoietic stimulating factor treatment within 14 days):(1)Hematology: a. Absolute neutrophil count ≥1.5×109/L; b. Platelet count ≥100×109/L; c. Hemoglobin ≥90 g/L.(2)Liver function: a. Total bilirubin ≤1.0×ULN; for participants with metastases to liver, total bilirubin ≤1.5×ULN; b. Alanine aminotransferase and aspartate aminotransferase ≤1.5×ULN, for participants with metastases to liver, alanine aminotransferase and aspartate aminotransferase ≤2.5×ULN. (3)Renal function: Creatinine ≤1.5×ULN; or creatinine clearance ≥50 mL/min (calculated according to the Cockcroft-Gault formula).(4)Coagulation function: International normalized ratio (INR) ≤ 1.5×ULN; activated partial thromboplastin time (APTT) ≤ 1.5×ULN; 8. Women of childbearing potential must use highly effective contraception.
Exclusion criteria
1. Previously received EGFR monoclonal antibody therapy for recurrent/metastatic nasopharyngeal cancer; 2. Have previously received treatment with doxorubicin or other anthracyclines, and the cumulative dose of doxorubicin exceeds 350 mg/m2 (Equivalent dose calculation for anthracyclines: 1 mg doxorubicin = 2 mg epirubicin = 2 mg daunorubicin = 0.5 mg idarubicin = 0.45 mg mitoxantrone); 3. History of drug allergy to the active or inactive excipients of any study drug, or to drugs with similar chemical structure or class as these two drugs; 4. Have received anti-tumor treatments within 2 weeks prior to the first dose of study drug, including hormone therapy, biological therapy, immunization therapy, local perfusion of anti-tumor drugs, or traditional Chinese medicines and/or Chinese patent drugs indicated for the treatment of nasopharyngeal cancer; 5. Have received local radiotherapy (including radionuclide therapy such as strontium-89) within 2 weeks prior to the first dose of study drug; have received irradiation of more than 30% of bone marrow or have received wide-field radiotherapy within 4 weeks prior to randomization; 6. Uncontrolled serous cavity effusions requiring frequent drainage or medical intervention within 14 days prior to the first dose; 7. Have undergone major surgery or had severe traumatic injury within 4 weeks prior to the first dose of study drug, or it is expected to undergo major surgery during the study period. Some clinical procedures such as vascular access placement and aspiration biopsy are allowed; 8. Currently receiving long-term immunosuppression therapy (e.g., cyclosporine) or have other diseases requiring treatment with systemic corticosteroids (i.e., prednisone over 10 mg/day or other corticosteroids at equivalent physiological doses), excluding those receiving local glucocorticoid therapy via nasal spray, inhalation, or other routes; 9. Participants with metastases to meninges or spinal cord compression; participants with symptomatic and/or unstable brain metastasis, unless the participant has completed definitive treatment and has been stable for at least 2 weeks prior to randomization without the need for steroid therapy. Participants with asymptomatic brain metastases may be enrolled if the investigator assesses that there is no indication for immediate curative treatment; 10. Subjects who have taken strong CYP3A4 inducers or inhibitors within 2 weeks prior to the first dose of study drug, or who cannot suspend the use of strong CYP3A4 inducers and inhibitors during the study; 11. Participants with a history of autoimmune diseases, a history of immunodeficiency, including positive for HIV, or other acquired or immunodeficiency congenital diseases, or a history of organ transplant; 12. Presence of active infection (e.g., the subject is receiving anti-infection therapy), including uncontrolled active hepatitis b, active hepatitis c, active syphilis, active tuberculosis, etc.; Patients with a history of human hepatitis B virus (HBV) infection may be considered for enrollment if they meet all of the following criteria: a. Have no co-infection with hepatitis C virus (HCV) and no history of HCV infection; b. Participants with active HBV infection may also be enrolled if they can receive at least 2 weeks of antiviral therapy before starting study treatment, and after treatment their HBV DNA is less than 100 IU/mL and transaminases are less than 1×ULN. 13. Severe or uncontrolled cardiovascular disorder requiring treatment, including but not limited to 14. Refractory nausea, vomiting, chronic gastrointestinal disease, inability to swallow drugs orally, or previous subtotal small bowel resection, etc., and have conditions that seriously affect gastrointestinal absorption as judged by the investigator. 15. Prior to initiating treatment, have not yet adequately recovered (i.e., to ≤ Grade 1, excluding hypodynamia or alopecia) from toxicities and/or complications caused by any interventions; 16. Participants with other malignant tumors currently or with a history of other active malignant tumors within 5 years prior to the first study treatment (except for clinically cured localized tumors; 17. History of interstitial lung disease (ILD), history of drug-induced ILD, history of radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD; 18. Women who are pregnant or breastfeeding; 19. The researchers believe that the subjects are not suitable to participate in this clinical study due to other reasons.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) per RECIST v1.1 | Up to approximately 30 months after the first participant is enrolled |
Secondary
| Measure | Time frame |
|---|---|
| Duration of response (DoR) per RECIST 1.1 | Up to approximately 30 months after the first participant is enrolled |
| Progression free survival (PFS) per RECIST 1.1 | Up to approximately 30 months after the first participant is enrolled |
| Overall survival(OS) | Up to approximately 30 months after the first participant is enrolled |
| Disease control rate (DCR) per RECIST 1.1 | Up to approximately 30 months after the first participant is enrolled |
| The plasma concentrations of JMT101, total mitoxantrone, and free mitoxantrone | Up to approximately 15 months after the first participant is enrolled |
| The incidence of JMT101 anti-drug antibodies (ADAs), titers, and neutralizing antibodies (NAbs, if applicable) | Up to approximately 15 months after the first participant is enrolled |
| The correlation between EGFR expression level and efficacy | Up to approximately 15 months after the first participant is enrolled |
| Frequency and severity of AEs (NCI CTCAE 5.0) | Up to approximately 30 months after the first participant is enrolled |
Contacts
Primary ContactClinical Trials Information Group officer
Outcome results
None listed