Camrelizumab With Famitinib for Patients With Rare Head and Neck Malignancies

A Prospective, Multi-Cohort Study of Camrelizumab in Combination With Famitinib for the Treatment of Patients With Rare Head and Neck Malignancies

This is a prospective, multicenter, multi-cohort, Phase II clinical trial enrolling patients with unresectable, recurrent, or metastatic soft tissue sarcoma, malignant melanoma, adenoid cystic carcinoma, or salivary gland malignancies (excluding adenoid cystic carcinoma) who have not previously received PD-1 inhibitor therapy. The planned sample size is 10 subjects per cohort, for a total of 40 subjects. Investigators may adjust the cohort sample sizes based on actual enrollment. Potentially eligible subjects will be screened within 4 weeks prior to the first dose to assess their eligibility for study entry. Subjects confirmed by the investigator to meet all inclusion criteria and none of the exclusion criteria will receive the investigational medicinal products as per the study design and undergo efficacy and safety assessments. This trial will consist of three periods: Screening/Baseline Period, Treatment Period, and Follow-up Period. The study procedures include: Screening Period: From the signing of the informed consent form up to 28 days prior to the first dose; Treatment Period: Treatment discontinuation is defined as the cessation of treatment for any reason, such as disease progression or intolerance, or premature withdrawal for any reason; Follow-up Period: Following the subject's last dose, safety follow-up will be initiated to monitor the resolution of adverse events. The first safety follow-up visit will occur 30 ± 7 days after the last study dose (calculated based on the later date of 30 days post the last dose of either camrelizumab or famitinib). Subjects are required to return to the study center for this safety follow-up, regardless of whether they have initiated new antineoplastic therapy. The subsequent two safety visits (60 ± 7 days and 90 ± 7 days after the last dose) may be conducted via telephone. After study discontinuation, survival follow-up will be conducted every 3 months to monitor survival status and subsequent antineoplastic treatments. The dosing regimen is as follows: camrelizumab 200 mg, IV, on Day 1, Q3W; famitinib 10 mg, PO, QD, Q3W, with 21 days constituting one treatment cycle. Study drugs should be administered at approximately the same time each day. If a patient vomits or misses a dose, no replacement dose should be taken on that day, and the next scheduled dose should be taken as usual. Subjects will continue treatment with camrelizumab and famitinib until discontinuation criteria are met. Clinical tumor imaging assessments will be performed every 2 cycles according to RECIST v1.1 (Appendix IV). Additionally, on Day 1 of each treatment cycle, clinically required assessments must be completed, including vital signs, physical examination, complete blood count, urinalysis, fecal occult blood test, hepatic and renal function tests, serum electrolytes, serum proteins, coagulation profile, serum tumor markers, thyroid function, electrocardiogram (ECG), and ECOG performance status score (specific assessments for each visit are detailed in the Schedule of Assessments). Hepatitis virus carriers will also require viral load monitoring every 2 to 4 treatment cycles.

Inclusion Criteria:

• Age ≥18 years; Histologically or cytologically confirmed unresectable or recurrent/metastatic soft tissue sarcoma, malignant melanoma, adenoid cystic carcinoma, or salivary gland carcinoma (non-adenoid cystic carcinoma) with no indication for curative treatment; Salivary gland tumors must be negative for both HER2 and AR, as determined by IHC; ECOG PS of 0-1; At least one measurable lesion according to RECIST v1.1 criteria; No prior PD-1 inhibitor therapy; Received ≤1 prior systemic therapy regimen; Adequate organ function, as defined by the following laboratory values: Organ Laboratory Value Hematology Absolute neutrophil count ≥1500/μL (1.5×10^9/L) Platelets ≥100,000/μL (100×10^9/L) Hemoglobin ≥9 g/dL (90 g/L) or ≥5.6 mmol/L Renal Creatinine or Creatinine clearance Creatinine ≤1.5×ULN; if creatinine >1.5×ULN, then creatinine clearance ≥60 mL/min Hepatic Total bilirubin ≤1.5×ULN AST and ALT ≤2.5×ULN, or ≤5×ULN in the presence of liver metastases Coagulation INR or PT ≤1.5×ULN; for patients receiving anticoagulants, PT or PTT must be within the therapeutic range of the anticoagulant being used Female subjects must have a negative pregnancy test within 2 weeks prior to the start of study treatment and must not be breastfeeding. Female subjects must agree to use highly effective contraceptive measures during the study and for 6 months after the last dose of study drug. Male subjects must agree to use highly effective contraceptive measures during the study and for 6 months after the last dose of study drug; Subject voluntarily agrees to participate in the study, provides written informed consent, and is able to comply with the protocol-specified visits and related procedures.

Exclusion Criteria:

• Radiotherapy or other local therapy (e.g., surgery) within 2 weeks prior to enrollment, or failure to recover from adverse events of prior therapy (i.e., to ≤Grade 1 or baseline); Participation in a clinical trial within 4 weeks prior to enrollment; Poorly controlled cardiac symptoms or diseases, including: (1) NYHA Class II or higher heart failure or LVEF <50% on echocardiography; (2) unstable angina; (3) myocardial infarction within 1 year prior to study treatment; (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; (5) QTc >450 ms (males) or QTc >470 ms (females) (QTc interval calculated using the Fridericia formula; if QTc is abnormal, three consecutive measurements at 2-minute intervals may be taken and averaged).

Hypertension that cannot be controlled to within the normal range with antihypertensive medication (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, based on the average of ≥2 BP readings); use of antihypertensive therapy to achieve these parameters is permitted. History of hypertensive crisis or hypertensive encephalopathy.

Presence of multiple factors affecting oral drug absorption (e.g., inability to swallow, nausea and vomiting, chronic diarrhea, intestinal obstruction, etc.).

Thrombotic or embolic events within 6 months prior to study treatment, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc.

Current interstitial pneumonitis or interstitial lung disease, or a history of interstitial pneumonitis or interstitial lung disease requiring corticosteroid therapy, or other conditions such as pulmonary fibrosis, organizing pneumonia, pneumoconiosis, drug-induced pneumonitis, or idiopathic pneumonitis that may interfere with the assessment and management of immune-related pulmonary toxicity, or evidence of active pneumonitis or severely impaired pulmonary function on chest CT at screening. Prior radiation pneumonitis in the radiation field is permitted; active tuberculosis.

Investigator-assessed life expectancy of less than 3 months, or rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain, etc.); Abnormal coagulation function (INR >1.5×ULN, APTT >1.5×ULN) or bleeding tendency; Diagnosis of immunodeficiency within 7 days prior to enrollment, or receiving systemic corticosteroid therapy or other forms of immunosuppressive therapy.

Diagnosis of other malignancies within 5 years prior to enrollment, except for cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, or other cured tumors that the investigator considers acceptable for exclusion.

Known active central nervous system metastases; Tumor invasion of major blood vessels or tumor ulceration with bleeding, as judged by the investigator; Active autoimmune disease requiring systemic therapy within 2 years prior to enrollment; History of allogeneic tissue transplantation or solid organ transplantation; Active infection requiring systemic therapy; Psychiatric illness or substance abuse that would interfere with trial compliance or cooperation; Positive serology for HIV or a history of HIV infection; Active HBV or HCV infection; Receipt of a live vaccine within 30 days prior to the start of the trial. Other factors, such as medical history, that in the investigator's assessment could compromise subject safety or affect trial evaluations.