A Clinical Trial to Evaluate Effect of IAE0972 Combined with Chemotherapy for R/M HNSCC or NPC(Note: It is Currently Phase II.).

Phase 2

Not yet recruiting

• Conditions: NPC; HNSCC; Recurrence; Metastasis
• Interventions: Biological: IAE0972+Docetaxel; Biological: IAE0972+ Methotrexate; Biological: IAE0972+Gemcitabine; Biological: IAE0972+Taxanes; Biological: IAE0972+Capecitabine

• Registration Number: NCT06719479
• Lead Sponsor: SUNHO（China）BioPharmaceutical CO., Ltd.

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.

Study Timeline

• Study First Submitted: 2024-11-27
• Status Verified: 2024-12
• Study First Submitted QC: 2024-12-02
• Last Update Submitted: 2024-12-02
• Study First Posted: 2024-12-05
• Last Update Posted: 2024-12-05
• Study Start: 2025-01-01
• Primary Completion: 2028-01-01
• Study Completion: 2028-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. The age is 18~75 years old (including the critical value), regardless of gender.

2. 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.

3. 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.

4. According to the researcher's judgment, the chemotherapy in this experiment is applicable.

5. 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).

6. The score of physical condition of the ECOG is 0~1.

7. The estimated survival time is ≥3 months.

8. 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);

       • Coagulation function: INR≤1.5 times ULN, APTT≤1.5 times ULN, and INR and APTT≤2.5 times ULN for patients with liver metastasis or liver cancer.

9. Qualified fertile subjects (male and female) must agree to use reliable contraceptive methods (hormone or barrier method or abstinence) with their partners during the trial and at least 6 months after the last medication; The blood pregnancy test of female subjects of childbearing age must be negative within 7 days before the first use of the study drug.

10. Subjects must give informed consent to this study before the experiment, and voluntarily sign a written informed consent form.

Exclusion Criteria

1. 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.

2. Received other unlisted clinical research drugs or treatments within 4 weeks before using the research drugs.

3. 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.).

4. 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.

5. 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.

6. 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).

7. Treatment with other immunosuppressants within 28 days or 5 half-lives (whichever is longer) before the first use of the study drug.

8. Have used immunomodulatory drugs within 14 days before the first use of the study drug (Appendix 5).

9. Have been vaccinated with any live vaccine within 4 weeks before the first use of the study drug.

10. Received allogeneic hematopoietic stem cell transplantation or organ transplantation in the past.

11. Brain parenchymal metastasis or meningeal metastasis with clinical symptoms.

12. It has active infection and needs intravenous anti-infection treatment at present.

13. Have a history of immunodeficiency disease, including positive detection of HIV antibody.

14. Active hepatitis B (HBsAg positive and HBV-DNA positive or above the upper limit of normal value) and active hepatitis C (HCV antibody positive and HCV RNA positive or above the upper limit of normal value).

15. Having serious and uncontrollable lung diseases (severe infectious pneumonia, interstitial lung disease, etc.).

16. Have a serious history of cardiovascular and cerebrovascular diseases, including but not limited to:

    ① Severe cardiac rhythm or conduction abnormality, such as ventricular arrhythmia requiring clinical intervention and II-III degree atrioventricular block;

    ② The mean QT interval (QTcF) corrected by Fridericia method was≥470 ms；

    ③ Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other cardiovascular and cerebrovascular events of grade 3 or above occurred within 6 months before the first administration; (4) There is heart failure or LVEF less than 50% with the NYHA cardiac function classification ≥II or structural heart disease with high risk judged by other researchers;

    ⑤ Clinically uncontrollable hypertension.

17. Suffering from active autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), with the exception of clinically stable autoimmune thyroiditis, type I diabetes, vitiligo, cured atopic dermatitis in children, psoriasis that does not require systemic treatment (within the past 2 years), etc.

18. Suffering from other malignant tumors within 5 years before the start of study administration, except for the following cases: malignant tumors that can be expected to be cured after treatment (including but not limited to thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer or breast ductal carcinoma in situ treated by radical surgery).

19. There is clinically uncontrollable effusion in the third space, which is judged by the researcher to be unsuitable for the group.

20. Known alcohol or drug dependence.

21. Have mental disorder or poor compliance.

22. Pregnant or lactating women.

23. The researcher thinks that the subject has other serious history of systemic diseases, or is not suitable to participate in this clinical study for other reasons.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 2	IAE0972+Docetaxel	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.
Cohort 1	IAE0972+ Methotrexate	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.
Cohort 3	IAE0972+Gemcitabine	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.
Cohort 4	IAE0972+Taxanes	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.
Cohort 5	IAE0972+Capecitabine	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.

Primary Outcome Measures

Name	Time	Method
Number of participants with treatment-related adverse events assessed by CTCAE v5.0.	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 Outcome Measures

Name	Time	Method
Overall survival (OS)	up to 2 years	OS is defined as the time from the date of first dosing to death from any cause
Objective response rate (ORR)	up to 2 years	ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1
Disease control rate (DCR)	up to 2 years	DCR is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1
Progression-free survival (PFS)	up to 2 years	PFS is defined as the time from the date of first dosing till the first documentation of disease progression (per RECIST v1.1 criteria) or death from any cause (whichever occurs first)