A Study of IMC-002 in Patients With Advanced Cancer Failed to Standard Therapy

Официальное название

An Open-Label, Dose-Escalation and Expansion, Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Clinical Activity of IMC-002 in Patients With Advanced Cancer Failed to Standard Therapy

Обзор

This is an Open-Label, Dose-Escalation and Expansion, Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Clinical Activity of IMC-002 in Patients with Advanced Cancer Failed to Standard Therapy

Подробное описание

The purpose of this study is to evaluate safety and tolerability and to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of IMC-002.

Multiple-dose levels of IMC-002 will be tested in subjects with advanced cancer.

Вмешательства

• Биопрепарат IMC-002
  Part 1: Dose escalation IMC-002 5, 10, 20, and 30 mg/kg over 3 hours (±30 minutes) intravenous (IV) infusion every 2 weeks Part 2: Expansion cohort IMC-002 20 mg/kg over 3 hours (±30 minutes) IV infusion at the first cycle, if the first infusion is tolerated, then over 1 to 1.5 hours (±10 minutes) IV infusion at all following cycles every 3 weeks In hepatocellular (HCC) Cohort, Lenvatinib 8 mg once daily (body weight of \< 60 kg), or 12 mg once daily (body weight of ≥ 60 kg) In triple negative b

Первичные конечные точки

• Incidence of Dose-Limiting Toxicities (DLTs) [Срок оценки: 21 days]
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [Срок оценки: through study completion, an average of 1 year]

Вторичные конечные точки (12)

• Pharmacokinetics Endpoint : Cmax [Срок оценки: through study completion, an average of 1 year]
• Pharmacokinetics Endpoint : Ctrough [Срок оценки: through study completion, an average of 1 year]
• Pharmacokinetics Endpoint : Tmax [Срок оценки: through study completion, an average of 1 year]
• Pharmacokinetics Endpoint : AUC [Срок оценки: through study completion, an average of 1 year]
• Pharmacokinetics Endpoint : CL [Срок оценки: through study completion, an average of 1 year]
• Pharmacokinetics Endpoint : t½ [Срок оценки: through study completion, an average of 1 year]
• Efficacy endpoints based on tumor assessment (Part2) : BOR [Срок оценки: Tumor assessments will be conducted every 2 cycles by contrast-enhanced CT (solid tumor), and every 3 cycles by PET-CT/CT with contrast (B-cell lymphoma), within 5 days prior to Day 1 of the next cycle, through study completion, an average of 1 year.]
• Efficacy endpoints based on tumor assessment (Part2) : ORR [Срок оценки: Tumor assessments will be conducted every 2 cycles by contrast-enhanced CT (solid tumor), and every 3 cycles by PET-CT/CT with contrast (B-cell lymphoma), within 5 days prior to Day 1 of the next cycle, through study completion, an average of 1 year.]
• Efficacy endpoints based on tumor assessment (Part2) : DCR [Срок оценки: Tumor assessments will be conducted every 2 cycles by contrast-enhanced CT (solid tumor), and every 3 cycles by PET-CT/CT with contrast (B-cell lymphoma), within 5 days prior to Day 1 of the next cycle, through study completion, an average of 1 year.]
• Efficacy endpoints based on tumor assessment (Part2) : DOR [Срок оценки: Tumor assessments will be conducted every 2 cycles by contrast-enhanced CT (solid tumor), and every 3 cycles by PET-CT/CT with contrast (B-cell lymphoma), within 5 days prior to Day 1 of the next cycle, through study completion, an average of 1 year.]
• Efficacy endpoints based on tumor assessment (Part2) : TTP [Срок оценки: Tumor assessments will be conducted every 2 cycles by contrast-enhanced CT (solid tumor), and every 3 cycles by PET-CT/CT with contrast (B-cell lymphoma), within 5 days prior to Day 1 of the next cycle, through study completion, an average of 1 year.]
• Efficacy endpoints based on tumor assessment (Part2) : PFS [Срок оценки: Tumor assessments will be conducted every 2 cycles by contrast-enhanced CT (solid tumor), and every 3 cycles by PET-CT/CT with contrast (B-cell lymphoma), within 5 days prior to Day 1 of the next cycle, through study completion, an average of 1 year.]

Критерии участия

Критерии включения

• Signed ICF
• Adult (19 years or older)
• Diagnosis and prior therapies

3-1. Part 1: Histologically or cytologically proven metastatic or locally advanced solid tumors

3-2. Part 2, HCC Cohort:

• Histologically or cytologically proven metastatic or locally advanced of hepatocellular carcinoma (excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors)
• Received ≥1 prior systemic therapy; lenvatinib-naive and eligible for lenvatinib.
• Child Pugh classification A

3-3. Part 2, TNBC Cohort:

• Histologically or cytologically proven metastatic or locally advanced of triple negative breast cancer: negative of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2)
• Received ≥1 prior systemic regimen and eligible for paclitaxel or gemcitabine/carboplatin. Patients who have previously received the planned SOC in this study (paclitaxel or gemcitabine/carboplatin) cannot be enrolled. If at least 6 months have elapsed since the completion of a prior SOC (paclitaxel, gemcitabine, and/or carboplatin) and the patient showed a tumor response to that regimen, the same SOC can be used in this trial.
• Bisphosphonate or denosumab for bone metastases is allowed if started before Cycle 1 Day 1. Prophylactic use of bisphosphonates or denosumab in patients without bone diseases is not permitted, except for the treatment of osteoporosis.

3-4. Part 2, BTC Cohort:

• Histologically or cytologically proven metastatic or locally advanced of biliary tract cancer (gallbladder cancer, cholangiocarcinoma)
• Received ≥1 prior systemic therapy; lenvatinib-naive and eligible for lenvatinib

3-5. Part 2, B-cell lymphoma Cohort:

• Histologically or cytologically proven CD20+ mature B-cell lymphoma according to 2016 WHO classification including:

• diffuse large B-cell lymphoma (de novo or transformed)
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma (nodal, extranodal or mucosa associated)
• Received ≥2 prior systemic therapies and eligible for rituximab treatment

• For all cancer type, neo-adjuvant and/or adjuvant chemotherapy is not regarded as chemotherapeutic regimen for metastatic or recurrent cancer unless recurrence within 6 months after the last dose of anti-cancer drugs as neo-adjuvant and/or adjuvant therapy.
• Subject must have at least 1 measurable lesion by RECIST 1.1
• Availability of tumor archival material or fresh biopsies
• ECOG performance status 0 or 1 and life expectancy ≥3 months
• Adequate hematologic function, hepatic function, and renal function
• Prior RT permitted if measurable disease exists outside the RT field or if disease progressed post-RT. RT must be completed ≥4 weeks before Cycle 1 Day 1
• Agree to use effective contraception
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Критерии исключения

• Treatment with nonpermitted drugs
• Prior treatment with a CD47 or SIRPα targeting agent
• Concurrent anticancer treatments
• Major surgery or significant traumatic injury prior to Screening or planned major surgery during the study period
• Previous malignant disease other than the target malignancy for this study
• Active infection requiring systemic therapy before Day 1
• Any active autoimmune disease, or history of autoimmune disease
• Any psychiatric or cognitive condition
• Known severe hypersensitivity reaction
• Pregnant or lactating
• Currently enrolled in another clinical study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

South Korea · 3 центра

• National Cancer Center — Goyang-si
• Asan Medical Center, Republic of Korea — Seoul
• Samsung Medical Center — Seoul

Публикации

• J.S.Ahn, et al. Enhanced Safety Profile of IMC-002, an Affinity-Optimized Anti-CD47 Antibody: Preclinical and Phase 1a/1b Findings. ESMO; 2025; Berlin, Germany. Abstract 1554P.
• J.Y.Hong, et al. Phase 1b Dose Extension Study of a Next-Generation Anti-CD47 Monoclonal Antibody IMC-002 Combined with Lenvatinib in Patients with Advanced Hepatocellular Carcinoma (HCC). ASCO; 2025; Chicago, IL, USA. Abstract 2526.
• Jiyea Choi, et al. Development of IMC-002, a next-generation anti-CD47 mAb: An affinity optimized antibody with enhanced safety and therapeutic efficacy in preclinical models. AACR; 2025; Chicago, IL, USA.. Abstract 4789.
• Jeong S, Lee SY, Kim SH, Kim HT, Yun HY, Chae JW, Lee S. Model-Informed Optimal Dosing of Anti-CD47 Antibody Using Target-Mediated Drug Disposition Model. Clin Transl Sci. 2025 Aug;18(8):e70321. doi: 10.1111/cts.70321. PMID 40841178
• H.Y.Lim, et al. Updated Safety, Efficacy, Pharmacokinetics, and Biomarkers from The Phase 1 Study of IMC-002, a Novel Anti-CD47 Monoclonal Antibody, in Patients with Advanced Solid Tumors. ASCO; 2024; Chicago, IL, USA. Abstract 2642.
• H.Y.Lim, et al. Phase 1 dose escalation study of IMC-002, a novel anti-CD47 monoclonal antibody, in patients with advanced solid tumors. ESMO; 2023; Madrid, Spain. Abstract 1035P.
• Ahn JS, Hong JY, Park JO, Lee SY, Kim S, Yun HY, Ock CY, Hwang W, Kim SH, Kim HT, Lim HY. Phase 1 Study of IMC-002, a Next-Generation Anti-CD47 Antibody, in Advanced Solid Tumors. Cancer Res Treat. 2025 Nov 4. doi: 10.4143/crt.2025.820. Online ahead of print. PMID 41197525

Идентификаторы

NCT: NCT05276310 · IMC-002-K102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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