A Study of IMM2510 + IMM27M Combination Therapy in Patients With Advanced Solid Tumors

NCT06764836 | Recruiting Phase 1

• 1 other identifier: IMM2510-002
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label, multi-centre, single-arm, phase I clinical study, to evaluate the safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of IMM2510 (an anti-PD-L1/VEGF bispecific antibody fusion protein) + IMM27M (a humanized Fc-engineered anti-CTLA-4 antibody) combination therapy in patients with advanced solid tumors.

Conditions

Advanced Solid Tumors; HCC

Outcome Measures

Primary Outcomes (3)

• DLT/MTD (Dose Escalation Phase)

  Incidence and characteristics of Dose-Limiting Toxicity (DLT) to determine the Maximum Tolerated Dose (MTD).

  Within 8 weeks after the investigational products administration (within 56 days after first dosing of C1D1)

• RP2D (Dose Extension Phase)

  Recommended Phase II Dose (RP2D) of IMM27M and IMM2510, as the dose for efficacy study in Phase II, will be the dose with promising clinical responses observed in the patients, and well tolerated by patients.

  From the first dose until disease progresses or end of treatment for other reasons, the maximum treatment duration is not more than 48 weeks

• Incidence and characteristics of AEs and SAEs (according to NCI CTCAE 5.0)

  Incidence and characteristics of Adverse Events (AEs) and Serious Adverse Events (SAEs) throughout the study period, were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0.

  From the first dose to 30 days after the last dose [90 days for SAEs and Immune-related Adverse Event (irAEs) ], or until beginning new anti-tumor treatment

Secondary Outcomes (16)

• ORR

  From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first, assessed up to approximately 2 years

• DCR

  From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first, assessed up to approximately 2 years

• DOR

  From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first, assessed up to approximately 2 years

• PFS

  From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first, assessed up to approximately 2 years

• OS

  From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first, assessed up to approximately 2 years

Study Arms (1)

IMM2510 + IMM27M Combination Therapy

EXPERIMENTAL

Dose Escalation Phase: Participants will receive IMM27M 3.0 mg/kg single dose on day 1 (C1D1), and after a 4-week interval, will receive IMM2510 10.0 mg/kg or 20.0 mg/kg dose every 2 weeks (Q2W). Dose Expansion Phase: The dose of IMM27M and IMM2510 for the dose expansion phase is determined according to the dose escalation results. Participants will receive IMM27M single dose on day 1 (C1D1), and after a 4-week interval, will receive IMM2510 every 2 weeks (Q2W).

Drug: IMM27M; Drug: IMM2510

Interventions

IMM27M DRUG

Intravenous injection

IMM2510 + IMM27M Combination Therapy

IMM2510 DRUG

Intravenous injection

IMM2510 + IMM27M Combination Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient can understand the procedures and methods of this clinical trial. After giving full informed consent, the patient voluntarily participates in it and signs the informed consent form.
• Aged between 18 and 75 years old (including both ends), regardless of gender.
• Clinical diagnosis:
• Dose escalation phase: Patients with advanced malignant solid tumors confirmed by histology or cytology, who have failed previous standard treatments, have no standard treatment regimens or are not suitable for standard treatment at present, including but not limited to hepatocellular carcinoma, triple-negative breast cancer, soft tissue sarcoma, non-small cell lung cancer, epithelial ovarian cancer, small cell lung cancer, malignant melanoma, colorectal cancer, ovarian cancer, endometrial cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, etc.
• Dose expansion phase: The following tumor types are included: a. Patients with advanced hepatocellular carcinoma who have failed or could not tolerate at least one line of previous systemic treatment; b. Patients with locally advanced, unresectable or metastatic triple-negative breast cancer confirmed by histology or cytology, who have failed or could not tolerate at least one line of previous systemic treatment; c. Patients with other advanced malignant solid tumors (except those with triple-negative breast cancer and advanced hepatocellular carcinoma) confirmed by histology or cytology, who have failed or could not tolerate at least one line of previous systemic treatment, including but not limited to soft tissue sarcoma, non-small cell lung cancer, epithelial ovarian cancer, small cell lung cancer, malignant melanoma, colorectal cancer, ovarian cancer, endometrial cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, etc.
• Dose escalation phase: According to RECIST version 1.1, there should be at least one evaluable tumor lesion; Dose expansion phase: According to RECIST version 1.1, there should be at least one measurable tumor lesion.
• ECOG performance status score of 0 - 1.
• The expected survival time is more than 3 months.
• There should be sufficient organ function. Hematological system (without receiving blood transfusion or hematopoietic stimulating factor treatment within 14 days): Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, Platelet count (PLT) ≥ 100 × 10⁹/L, Hemoglobin (Hb) ≥ 90 g/L. For patients with HCC accompanied by liver cirrhosis, ANC ≥ 1.0 × 10⁹/L and platelet count ≥ 90 × 10⁹/L are acceptable for enrollment.
• Liver function: Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), for patients with liver metastasis or liver cancer, TBIL ≤ 3.0 × ULN; Alanine aminotransferase (ALT) ≤ 2.5 × ULN, for patients with liver metastasis or liver cancer, ALT ≤ 5.0 × ULN; Aspartate aminotransferase (AST) ≤ 2.5 × ULN, for patients with liver metastasis or liver cancer, AST ≤ 5.0 × ULN.
• Renal function: Creatinine clearance rate (Ccr) ≥ 50 ml/min (calculated according to the Cockcroft-Gault formula), Urinary protein \< 2+ or 24-hour urinary protein quantification \< 1.0 g.
• Coagulation function: Prothrombin time (PT) ≤ 1.5 × ULN, Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, International normalized ratio (INR) ≤ 1.5 × ULN.
• Cardiac function: 12-lead electrocardiogram, QTc interval ≤ 480 ms, Echocardiogram, Left ventricular ejection fraction (LVEF) ≥ 50%.
• Thyroid function: Thyroid-stimulating hormone (TSH) ≤ 1 × ULN (if abnormal, FT3 and FT4 levels should be observed simultaneously. If FT3 and FT4 levels are normal, enrollment is allowed).
• Liver function grading for HCC patients: Child-Pugh score ≤ 7 points.

You may not qualify if:

• Patients meeting any one of the following criteria will be excluded from this study:
• Previous treatment history:
• Patients who received mitomycin and nitrosourea chemotherapy within 6 weeks before the first administration.
• Patients who received the last systemic anti-tumor treatment, including chemotherapy, radiotherapy, immunotherapy, biological agents or endocrine therapy, etc., within 4 weeks before the first administration.
• Patients who received hormonal anti-tumor treatment or small molecule targeted therapy within 2 weeks before the first administration.
• Patients who received local treatment such as radiotherapy for target lesions within 4 weeks before the first administration, and those who received palliative local treatment for non-target lesions within 2 weeks before the first administration.
• Patients who received non-specific immunomodulatory treatment (such as interleukin, interferon, thymosin, tumor necrosis factor, etc., excluding IL-11 used for treating thrombocytopenia) within 2 weeks before the first administration.
• Patients who previously received the experimental drugs IMM2510 and/or IMM27M; those who could not tolerate treatment with anti-CTLA-4 or PD-1/L1 inhibitors (due to toxic and side effects); those who previously used drugs targeting three targets, namely anti-PD-1/L1, VEGF, and CTLA-4 simultaneously in the same regimen.
• Patients who received traditional Chinese medicine with anti-tumor indications within 1 week before the first administration.
• Patients who participated in other clinical trials within 4 weeks before the first administration.
• Those with a known severe allergic history to any component of the experimental drug, or those with a history of severe allergic reactions to chimeric or humanized antibodies or fusion proteins.
• Those who had any immune-related adverse events (irAE) of grade ≥ 3 in CTCAE V5.0 or that led to the termination of immunotherapy during previous treatment with any immunotherapy drugs.
• Those diagnosed with other malignant tumors within 5 years before enrollment. Exceptions: 1) Cervical carcinoma in situ and non-melanoma skin cancer that have been cured; 2) Patients who have been radically cured, unless the patients have been in complete remission for at least 2 years before enrollment and do not require other treatments or will not require other treatments during the study period.
• Those with an active second primary cancer that is known and has had no recurrence within 5 years. Exceptions: 1) The investigator believes that both primary cancers can benefit from this study; 2) The investigator has clearly excluded which primary tumor the metastatic lesions belong to.
• Patients with primary central nervous system (CNS) malignant tumors or those with active CNS metastases that failed local treatment (radiotherapy or surgical treatment). However, the following patients are allowed to enroll: a. Patients with asymptomatic brain metastases; b. Patients with clinically stable symptoms (i.e., no radiological progression was seen within 4 weeks before the first administration, and any neurological symptoms have returned to the baseline level), and who have not required corticosteroid hormones and other treatments for brain metastases for ≥ 4 weeks.

Sponsors & Collaborators

• ImmuneOnco Biopharmaceuticals (Shanghai) Inc.: lead

Study Sites (1)

ZhongShan Hospital Fudan University

Shanghai, Shanghai Municipality, China

RECRUITING

Central Study Contacts

Deqiang Jing, M.D., Ph.D

CONTACT

+86-021-38016378; deqiang.jing@immuneonco.com

Qiying Lu, M.D.

CONTACT

qiying.lu@immuneonco.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2024
• First Posted: January 8, 2025
• Study Start: July 23, 2024
• Primary Completion: January 27, 2026
• Study Completion: January 27, 2026
• Last Updated: January 8, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)