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A Study of QL1706 Combined With OH2 Injection in Perioperative Treatment of Stage III Resectable Acral Melanoma

2026년 10월 1일 업데이트: Peking University Cancer Hospital & Institute

Efficacy and Safety of Iparomlimab and Tuvonralimab Injection(Anti-PD-1/CTLA-4 Bispecific Antibody) Combined With Recombinant Human GM-CSF Oncolytic HSV-2 (OH2) Injection (Vero Cells) for Perioperative Treatment of Stage III Resectable Acral Melanoma: A Prospective, Randomized, Controlled, Multicenter Clinical Study

This is a prospective, multicenter, open-label, 1:1 randomized phase II trial enrolling 76 patients with AJCC stage III surgically resectable acral melanoma. Arm A receives neoadjuvant combination of intratumoral OH2 oncolytic HSV2 plus IV QL1706 (Iparomlimab and Tuvonralimab Injection) for 6 q2w cycles before radical surgery, followed by stratified QL1706 adjuvant therapy. Arm B undergoes upfront radical surgery followed by single-agent QL1706 adjuvant therapy for up to 1 year. The primary endpoint is 2-year EFS rate. Secondary endpoints include pathologic response, RFS, OS, and overall safety profile. All patients receive regular imaging follow-up up to 5 years post-surgery.

연구 개요

연구 유형

중재적

등록 (추정된)

76

단계

  • 4단계

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

  1. Voluntarily sign the written informed consent form.
  2. Male or female patients aged ≥18 years and ≤75 years at the time of enrollment.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  4. Histologically and/or cytologically confirmed resectable Stage III acral melanoma (according to the AJCC 8th edition staging system for cutaneous malignant melanoma) with at least one measurable lesion.
  5. Expected survival ≥4 months.
  6. Adequate organ function: a) Hematology (without any blood component or growth factor support within 7 days before the start of study treatment): i. Absolute neutrophil count (ANC) ≥1.5×10⁹/L (1,500/mm³); ii. White blood cell count ≥3.0×10⁹/L; iii. Platelet count >100×10⁹/L (100,000/mm³); iv. Hemoglobin ≥90 g/L. b) Renal: i. Serum creatinine ≤1.5×ULN, or 24-hour creatinine clearance ≥50 mL/min (calculated according to the Cockcroft-Gault formula); ii. Urine protein <2+ or 24-hour urine protein quantification <1.0 g. c) Hepatic: i. Serum total bilirubin (TBil) ≤1.5×ULN; ii. AST and ALT ≤2.5×ULN; iii. Serum albumin (ALB) ≥28 g/L. d) Coagulation: i. International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5×ULN (if the subject is receiving anticoagulant therapy, the subject must be on a stable dose of anticoagulant, and the coagulation parameters [PT/INR and APTT] at screening should be within the expected therapeutic range for the anticoagulant used). e) Cardiac function: i. Left ventricular ejection fraction (LVEF) ≥50%.

6、Female patients of childbearing potential (including those with premature menopause, menopause <2 years, and those who have not undergone surgical sterilization), male patients, and their partners must agree to use effective contraception during the study period, including surgical sterilization, oral contraceptives, intrauterine devices, abstinence, or barrier contraception combined with spermicide. All patients must continue contraception for 6 months after the last treatment.

8、Subjects with a history of genital herpes must have a 3-month interval after the herpes has resolved.

9、Subjects must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study requirements.

Exclusion Criteria:

  1. Patients who have previously received treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 agents.
  2. Patients whose lesions do not meet the volume requirements for intratumoral injection or are unsuitable for intratumoral injection.
  3. Patients who have received anti-herpes simplex virus therapy (e.g., acyclovir, ganciclovir, valacyclovir, vidarabine) within 4 weeks prior to randomization, except for patients with hepatitis B who are receiving ongoing treatment with entecavir, tenofovir disoproxil fumarate, or adefovir dipivoxil.
  4. Receipt of a live attenuated vaccine within 4 weeks prior to randomization.
  5. Use of an investigational drug within 4 weeks prior to randomization.
  6. Lesions that cannot accommodate an intratumoral injection volume of 1 mL.
  7. Receipt of another anti-tumor monoclonal antibody (mAb) therapy within 4 weeks prior to randomization, or failure of adverse events from prior therapy (occurring more than 4 weeks earlier) to recover to ≤ Grade 1.
  8. Patients with a history of other malignancy (including unknown primary site) within 5 years prior to randomization. Note: Patients with curatively treated Stage 1 or 2 basal/squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ are excluded.
  9. Patients with known hypersensitivity to the investigational drug, its active ingredients, or excipients.
  10. Patients who are positive for hepatitis B surface antigen (HBsAg) with a hepatitis B virus DNA copy number >1×10³ copies/mL; patients who test positive for hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) antibody.
  11. Patients with any unstable systemic disease, including but not limited to: severe infection, uncontrolled diabetes, unstable angina, cerebrovascular accident or transient ischemic attack, myocardial infarction, congestive heart failure, severe arrhythmia requiring medication, liver, kidney, or metabolic disease.
  12. Patients with active central nervous system (CNS) metastases. Patients with adequately treated CNS metastases whose neurological symptoms have recovered to ≤ Grade 1 (CTCAE criteria) for at least 2 weeks prior to randomization (excluding residual signs or symptoms related to CNS treatment) may participate in the study. In addition, patients must not be using corticosteroids, or must be on a stable dose of ≤10 mg prednisone/day (or equivalent), or must have tapered to ≤10 mg prednisone/day.
  13. Patients with autoimmune disease, history of liver or other organ transplantation, active tuberculosis; or patients who have undergone major surgery, live vaccination, or immunotherapy within 4 weeks prior to randomization.
  14. Tumor invasion of major blood vessels such as iliac or femoral vessels.
  15. Patients with diseases (e.g., mental illness) or conditions (e.g., alcoholism or drug abuse) that may increase the risk of study drug administration, affect study compliance, or interfere with the interpretation of study results.
  16. Patients who have received any other investigational product or participated in another interventional clinical trial within 30 days prior to the screening period.
  17. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study; male or female patients unwilling to use effective contraception. Other conditions deemed unsuitable for enrollment by the investigator.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: Experimental:(Neoadjuvant Therapy + Radical Surgery + Postoperative Adjuvant Therapy)

Patients receive 6 cycles of neoadjuvant therapy (QL1706 3 mg/kg IV Q2W + OH2 intratumoral injection up to 8 mL Q2W), followed by radical surgery within 2 weeks after the last neoadjuvant dose. Postoperatively, patients with pCR or near pCR receive observation and follow-up; patients with pPR or NR receive adjuvant QL1706 5 mg/kg IV Q3W for up to 1 year (calculated from the first neoadjuvant dose). BRAF-mutant recurrent patients receive dabrafenib + trametinib instead of QL1706 during adjuvant phase.

A PD-1/CTLA-4 combination antibody produced using MabPair® technology. It contains two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1) expressed at a fixed ratio from a single cell line. Administered intravenously. In the neoadjuvant phase: 3 mg/kg Q2W for 6 cycles. In the adjuvant phase: 5 mg/kg Q3W for up to 1 year. Manufactured by Qilu Pharmaceutical Co., Ltd. Supplied as 50 mg/2 mL vial. Store at 2-8°C, protect from light, do not freeze.

A genetically modified oncolytic type II herpes simplex virus (HSV2) strain HG52, with ICP34.5 and ICP47 genes deleted to enable selective replication in tumor cells and enhance antitumor immunity, and engineered to express human GM-CSF. Administered via intratumoral injection. Planned dose: 10^7 CCID50/mL, Q2W for up to 6 cycles. Maximum single-visit volume: 8 mL, adjusted based on lesion diameter. Dose may be reduced to 10^6 CCID50/mL in case of ≥ Grade 3 related AEs. Manufactured by Wuhan Binhui Bio-technology Co., Ltd. Supplied as 1 mL/vial. Store at -70°C or below.

활성 비교기: Active Comparator: (Radical Surgery + Postoperative Adjuvant Therapy)

Patients undergo radical surgery directly after enrollment. Postoperatively, all patients receive adjuvant QL1706 5 mg/kg IV Q3W for up to 1 year (calculated from the first adjuvant dose), unless contraindicated. BRAF-mutant recurrent patients receive dabrafenib + trametinib instead of QL1706 during adjuvant phase.

A PD-1/CTLA-4 combination antibody produced using MabPair® technology. It contains two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1) expressed at a fixed ratio from a single cell line. Administered intravenously. In the neoadjuvant phase: 3 mg/kg Q2W for 6 cycles. In the adjuvant phase: 5 mg/kg Q3W for up to 1 year. Manufactured by Qilu Pharmaceutical Co., Ltd. Supplied as 50 mg/2 mL vial. Store at 2-8°C, protect from light, do not freeze.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
2-Year Event-Free Survival Rate
기간: From randomization up to 2 years

Event-free survival (EFS) is defined as the time from randomization to the occurrence of any of the following events: disease progression leading to inoperability (development of locally unresectable disease or distant metastasis), local or distant recurrence, melanoma-related or treatment-related death. The occurrence of a new primary melanoma during treatment or follow-up will also be considered an event.

From randomization up to 2 years

2차 결과 측정

결과 측정
측정값 설명
기간
Pathologic Response Rate (pCR, Near pCR, pPR)
기간: At the time of surgery (approximately 12 weeks after enrollment)

Assessment is performed according to the International Neoadjuvant Melanoma Consortium (INMC) scoring system. Partial pathological response (pPR) is defined as viable tumor cells ≥10% and ≤50%. Near pathological complete response (near pCR) is defined as viable tumor cells >0% and <10%. Pathological complete response (pCR) is defined as the absence of viable tumor cells. The aim is to evaluate pathological response rates, including the partial pathological response rate, major pathological response/near pathological complete response rate, and pathological complete response rate.

At the time of surgery (approximately 12 weeks after enrollment)
Relapse-Free Survival (RFS)
기간: 5 years

The time from randomization to the first occurrence of any of the following events: disease recurrence (local, regional, or distant metastasis) or death from any cause, whichever occurs first.

5 years
Overall Survival (OS)
기간: 5 years

The time from randomization to death from any cause.

5 years
The incidence and severity of adverse events (AEs)
기간: 5 years

Safety

5 years

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 10월 1일

기본 완료 (추정된)

2029년 9월 1일

연구 완료 (추정된)

2030년 6월 1일

연구 등록 날짜

최초 제출

2026년 9월 28일

QC 기준을 충족하는 최초 제출

2026년 10월 1일

처음 게시됨 (실제)

2026년 10월 2일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 10월 2일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 10월 1일

마지막으로 확인됨

2026년 8월 1일

추가 정보

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