A Phase II/III Clinical Trial to Evaluate the Effect of IAE0972 Combined with Chemotherapy Selected by Doctors for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma/Nasopharyngeal Carcinoma.
Overview
- Phase
- Phase 2
- Intervention
- IAE0972+ Methotrexate
- Conditions
- NPC
- Sponsor
- SUNHO（China）BioPharmaceutical CO., Ltd.
- Enrollment
- 60
- Primary Endpoint
- Number of participants with treatment-related adverse events assessed by CTCAE v5.0.
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
Phase II: To evaluate the safety and tolerability of IAE0972 combined with chemotherapy selected by doctors for R/M HNSCC/NPC after failure or progress of ≤2-line system therapy, and to determine the MTD of combined therapy.
Phase III: According to the RECIST 1.1, the effectiveness of IAE0972 combined with chemotherapy regimen chosen by doctors compared with placebo plus chemotherapy regimen chosen by doctors was evaluated through OS in patients with R/M NPC who failed or progressed after treatment with ≤2-line system.
Detailed Description
The Phase II is the dose escalation study of IAE0972 combined with the chemotherapy chosen by doctors, aiming at evaluating the safety, tolerance and preliminary effectiveness for patients with R/M HNSCC/NPC;Phase III aims to evaluate the effectiveness and safety of IAE0972+ doctors' chemotherapy compared with doctors' chemotherapy in patients with R/M NPC who have failed or progressed after treatment with ≤2-line system through OS.In the study, the adverse events and reactions were evaluated by clinical observation, vital signs monitoring and laboratory examination, and related samples such as PK and ADA were collected. Taking RECIST 1.1 as the tumor evaluation standard, after the first infusion of the study drug, every two cycles (±7 days, before the next cycle of administration, and the day of administration in this cycle is defined as D1 of the current cycle), the subjects were evaluated for tumor until the disease progressed, new anti-tumor treatment was started, the researchers judged that it was not suitable to continue to participate (such as intolerable adverse reactions), lost the visit, and voluntarily withdrew.When the subject withdraws from or terminates the treatment (+7 days), the subject should be visited before starting the new anti-tumor treatment (except death and lost visit), and relevant laboratory tests and ADA sample collection should be carried out; After that, their OS was followed up by telephone every 12 weeks (±7 days) until they were lost or died.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The age is 18\~75 years old (including the critical value), regardless of gender.
- •Phase II cohort 1, cohort 2: locally advanced squamous cell carcinoma of the head and neck which only occurred in the oral cavity, oropharynx, hypopharynx and larynx after histological diagnosis or had no indication of radical local treatment; In the past, I only received ≤2 line therapy for recurrent and metastatic head and neck squamous cell carcinoma.
- •Phase II cohort 3, cohort 4, cohort 5: Histologically confirmed nasopharyngeal carcinoma, stage IVb or recurrent nasopharyngeal carcinoma that is not suitable for local treatment according to the TNM of AJCC nasopharyngeal carcinoma in the 8th edition of 2017; In the past, they only received ≤2 line therapy for recurrent and metastatic nasopharyngeal carcinoma.
- •According to the researcher's judgment, the chemotherapy in this experiment is applicable.
- •According to the RECIST 1.1 standard, there is at least one measurable lesion (tumor lesions located in previous radiotherapy areas or other local regional treatment sites are generally not regarded as measurable lesions, unless the lesions make clear progress or persist after radiotherapy for three months).
- •The score of physical condition of the ECOG is 0\~
- •The estimated survival time is ≥3 months.
- •Have sufficient organ functions:
- •Blood system (no blood transfusion or hematopoietic stimulating factor treatment within 14 days): ANC≥1.5×109/L, PLT≥90×109/L, HGB≥ 90 g/L; ② Liver function: TBIL≤1.5 times the ULN, except Gilbert syndrome; AST and ALT are ≤3.0 times ULN, while subjects with liver metastasis or liver cancer need AST and ALT≤3.0 times ULN and total bilirubin ≤ 3.0 times ULN;
- •Renal function: Cr≤1.5 times ULN; If the creatinine is more than 1.5 times ULN, the CCR should be ≥ 50 ml/min (calculated according to Cockcroft-Gault formula);
Exclusion Criteria
- •Having received chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy and other anti-tumor treatments within 4 weeks before the first use of the investigating drug, the following drugs should be excluded according to the following criteria:
- •① Nitrosourea or mitomycin C was used within 6 weeks before the first use of the study drug;
- •② Oral administration of fluorouracil and small molecule targeted drugs 2 weeks before the first use of the study drug or within 5 half-lives of the drug (whichever is longer);
- •③ Chinese patent drugs with anti-tumor indications were used within 2 weeks before the first use of the study drugs.
- •Received other unlisted clinical research drugs or treatments within 4 weeks before using the research drugs.
- •The adverse reactions of previous anti-tumor treatments have not recovered to NCI CTCAE 5.0 grade evaluation ≤1 grade or the relevant provisions of the selection criteria (except for the toxicity that the researchers judged to have no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, hypothyroidism stabilized by hormone replacement therapy, etc.).
- •It is known that it has hypersensitivity to any antibody drugs (NCI CTCAE 5.0 rating is ≥3), or it has hypersensitivity to research drugs, active ingredients or inactive excipients of chemotherapy schemes.
- •Have received major surgery (excluding puncture biopsy), major trauma or need to undergo elective surgery during the trial within 4 weeks before the first use of the study drug.
- •Having received systemic corticosteroids (prednisone \> 10 mg/day or similar drugs with the same dose) within 14 days before the first use of the study drug, except for the following cases: using topical, ophthalmic, intra-articular and intranasal corticosteroids; Short-term use of glucocorticoids for preventive treatment (for example, prevention of contrast agent allergy).
- •Treatment with other immunosuppressants within 28 days or 5 half-lives (whichever is longer) before the first use of the study drug.
Arms & Interventions
Cohort 1
In Phase II，the patients will receive the combined treatment of IAE0972（7.5 mg/kg、10 mg/kg、15 mg/kg、20 mg/kg）+ Methotrexate（Chemotherapy chosen by doctors）. Every 21 days is defined as a treatment cycle.
Intervention: IAE0972+ Methotrexate
Cohort 2
In Phase II，the patients will receive the combined treatment of IAE0972（7.5 mg/kg、10 mg/kg、15 mg/kg、20 mg/kg）+ Docetaxel（Chemotherapy chosen by doctors）. Every 21 days is defined as a treatment cycle.
Intervention: IAE0972+Docetaxel
Cohort 3
In Phase II，the patients will receive the combined treatment of IAE0972（7.5 mg/kg、10 mg/kg、15 mg/kg、20 mg/kg）+ Gemcitabine（Chemotherapy chosen by doctors）. Every 21 days is defined as a treatment cycle.
Intervention: IAE0972+Gemcitabine
Cohort 4
In Phase II，the patients will receive the combined treatment of IAE0972（7.5 mg/kg、10 mg/kg、15 mg/kg、20 mg/kg）+ Taxanes （Chemotherapy chosen by doctors）. Every 21 days is defined as a treatment cycle.
Intervention: IAE0972+Taxanes
Cohort 5
In Phase II，the patients will receive the combined treatment of IAE0972（7.5 mg/kg、10 mg/kg、15 mg/kg、20 mg/kg）+ Capecitabine（Chemotherapy chosen by doctors）. Every 21 days is defined as a treatment cycle.
Intervention: IAE0972+Capecitabine
Outcomes
Primary Outcomes
Number of participants with treatment-related adverse events assessed by CTCAE v5.0.
Time Frame: up to 2 years
AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.
Secondary Outcomes
- Overall survival (OS)(up to 2 years)
- Objective response rate (ORR)(up to 2 years)
- Disease control rate (DCR)(up to 2 years)
- Progression-free survival (PFS)(up to 2 years)