Clinical trial NCT06989671: SYS6002 Plus JMT101 and Enlonstobart Injection as First-Line Treatment for HNSCC
Official title: A Phase 2 Study of SYS6002 in Combination With JMT101 and Enlonstobart Injection as First-Line Treatment for Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Cancer (HNSCC)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Lead sponsor: CSPC Megalith Biopharmaceutical Co.,Ltd.
Sponsor class: INDUSTRY
First posted: 2025-05-25
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Randomized, open-label, factorial design
Primary purpose: TREATMENT

Brief summary: This is a Phase II study of anti-nectin-4 ADC combined with the EGFR monoclonal antibody and the PD-1 monoclonal antibody in patients with advanced head and neck squamous cell carcinoma who have not received previous systemic treatment

Detailed description: This trial is divided into two parts. Part 1 (combination therapy group) consists of Stage 1 (dose escalation) and Stage 2 (proof of conception study), in which Stage 2 adopts a randomized, controlled, open-label, multicenter design; Part 2 (monotherapy group) is SYS6002 monotherapy, divided into two cohorts with different dose groups. After completing the dose escalation of Part 1 (combination therapy group), and combining with the efficacy and safety data of SYS6002 monotherapy in Part 2 of this study and other clinical studies in participants with ≥2L HNSCC, the decision to enter Stage 2 in Part I (combination therapy group) will be made by discussion between the sponsor and the investigator.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or older, regardless of gender.
* Able to understand and voluntarily sign a written informed consent form (ICF).
* Confirmed recurrent or metastatic HNSCC that is not curable with local treatments. Primary tumor must be located in the oral cavity, oropharynx, hypopharynx, or larynx.
* Able to provide well-preserved or fresh tumor tissue.
* According to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, at least one measurable lesion confirmed by CT or MRI.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
* Expected survival time of ≥ 3 months.
* Normal major organ function within 7 days prior to treatment.

Exclusion Criteria:

* Primary tumor located in the nasopharynx, nasal cavity, paranasal sinuses, salivary glands, thyroid or parathyroid glands, skin, or squamous cell carcinoma with an unknown primary site.
* Presence of leptomeningeal metastasis, spinal cord compression, symptomatic or progressive brain metastases.
* (Only for Part 1) Prior systemic anti-tumor therapy for recurrent or metastatic HNSCC.
* Known allergy to any component of SYS6002, JMT101, or Enlonstobart injection.
* Participants who have previously received MMAE toxin ADC treatment (only for Part 2 participants).
* Adverse events related to prior anti-tumor treatment that have not resolved to ≤ Grade 1 according to NCI-CTCAE v5.0 (except for toxicities deemed low-risk by the investigator, such as Grade 2 alopecia).
* Washout period not met for anti-tumor medications or treatments.
* Any serious and/or uncontrolled comorbid conditions that may interfere with the participant's ability to participate in the study
* Pregnant or breastfeeding women; women of childbearing potential with a positive pregnancy test within 7 days before enrollment. Breastfeeding women may participate if they stop breastfeeding, but they cannot resume breastfeeding during the treatment and after the study ends.
* Any male or female participants of childbearing potential who refuse to use highly effective contraception during the study and for 6 months after the last dose of study drug.
* Unwilling or unable to comply with the study procedures and requirements, or deemed unsuitable for participation by the investigator.

Primary outcomes:
measure: Dose-limiting Toxicities (DLTs)
timeFrame: Up to 28 days
measure: Incidence of Adverse Events (AEs)
timeFrame: Up to approximately 2 years
measure: Maximum Tolerated Dose (MTD)
timeFrame: Up to approximately 2 years
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
Study officials:
References: