Studie IMC-002 u pacientů s pokročilou rakovinou selhala při standardní terapii
Otevřená, eskalace a expanze dávky, studie fáze I ke zkoumání bezpečnosti, snášenlivosti, farmakokinetiky a klinické aktivity IMC-002 u pacientů s pokročilou rakovinou, u kterých selhala standardní terapie
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
Přehled studie
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 1
Kontakty a umístění
Studijní kontakt
- Jméno: JIHEE KWON
- Telefonní číslo: +82 2 6283 5064
- E-mail: jhkwon@immuneoncia.com
Studijní místa
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-
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Goyang-si, Jižní Korea
- Aktivní, ne nábor
- National Cancer Center
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Seoul, Jižní Korea
- Nábor
- Samsung Medical Center
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Vrchní vyšetřovatel:
- Jung Yong Hong, MD
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Seoul, Jižní Korea
- Dokončeno
- Asan Medical Center, Republic of Korea
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
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Signed ICF
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Adult (19 years or older)
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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, PDAC Cohort:
- Histologically or cytologically proven metastatic or locally advanced of pancreatic ductal adenocarcinoma
- Must have received one or two prior anti-cancer systemic regimen and adequate for administration of lenvatinib.
3-6. Part 2, B-cell lymphoma Cohort:
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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)
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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.
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Subject must have at least 1 measurable lesion by RECIST 1.1
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Availability of tumor archival material or fresh biopsies
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ECOG performance status 0 or 1 and life expectancy ≥3 months
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Adequate hematologic function, hepatic function, and renal function
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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
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Agree to use effective contraception
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Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Exclusion Criteria:
- 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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: IMC-002
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 breast cancer (TNBC) Cohort, Paclitaxel 175 mg/m2 IV infusion on Day 1 of each cycle, or Gemcitabine 1,000 mg/m2 followed by Carboplatin AUC 2 IV infusion on Day 1 and Day 8 of each cycle In biliary tract cancer (BTC) and pancreatic ductal adenocarcinoma (PDAC) Cohort, Lenvatinib 8 mg once daily (body weight of < 60 kg), or 12 mg once daily (body weight of ≥ 60 kg) In B-cell lymphoma Cohort, Rituximab 375 mg/m2 IV infusion on Day 1 of each cycle |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Incidence of Dose-Limiting Toxicities (DLTs)
Časové okno: 21 days
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To determine maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of IMC-002 |
21 days
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Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Časové okno: through study completion, an average of 1 year
|
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through study completion, an average of 1 year
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Pharmacokinetics Endpoint : Cmax
Časové okno: through study completion, an average of 1 year
|
maximum observed serum concentration (Cmax) of IMC-002 |
through study completion, an average of 1 year
|
|
Pharmacokinetics Endpoint : Ctrough
Časové okno: through study completion, an average of 1 year
|
minimum observed serum concentration immediately before dosing (Ctrough) of IMC-002 |
through study completion, an average of 1 year
|
|
Pharmacokinetics Endpoint : Tmax
Časové okno: through study completion, an average of 1 year
|
time of the maximum observed serum concentration (Tmax) of IMC-002 |
through study completion, an average of 1 year
|
|
Pharmacokinetics Endpoint : AUC
Časové okno: through study completion, an average of 1 year
|
Area Under the Serum Concentration-Time Curve (AUC) of IMC-002 |
through study completion, an average of 1 year
|
|
Pharmacokinetics Endpoint : CL
Časové okno: through study completion, an average of 1 year
|
total body clearance (CL) of IMC-002 |
through study completion, an average of 1 year
|
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Pharmacokinetics Endpoint : t½
Časové okno: through study completion, an average of 1 year
|
terminal half-life (t½) of IMC-002 |
through study completion, an average of 1 year
|
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Efficacy endpoints based on tumor assessment (Part2) : BOR
Časové okno: 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.
|
best overall response (BOR) To evaluate efficacy of IMC-002 in combination with standard of care (SOC) anti-cancer therapy, as assessed by RECIST 1.1 (for solid tumors) or Lugano criteria (for B-cell lymphoma). |
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
Časové okno: 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.
|
objective response rate (ORR) To evaluate efficacy of IMC-002 in combination with standard of care (SOC) anti-cancer therapy, as assessed by RECIST 1.1 (for solid tumors) or Lugano criteria (for B-cell lymphoma). |
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
Časové okno: 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.
|
disease control rate (DCR) To evaluate efficacy of IMC-002 in combination with standard of care (SOC) anti-cancer therapy, as assessed by RECIST 1.1 (for solid tumors) or Lugano criteria (for B-cell lymphoma). |
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
Časové okno: 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.
|
duration of response (DOR) To evaluate efficacy of IMC-002 in combination with standard of care (SOC) anti-cancer therapy, as assessed by RECIST 1.1 (for solid tumors) or Lugano criteria (for B-cell lymphoma). |
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.
|
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Efficacy endpoints based on tumor assessment (Part2) : TTP
Časové okno: 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.
|
time-to-progression (TTP) To evaluate efficacy of IMC-002 in combination with standard of care (SOC) anti-cancer therapy, as assessed by RECIST 1.1 (for solid tumors) or Lugano criteria (for B-cell lymphoma). |
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
Časové okno: 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.
|
progression-free survival (PFS) To evaluate efficacy of IMC-002 in combination with standard of care (SOC) anti-cancer therapy, as assessed by RECIST 1.1 (for solid tumors) or Lugano criteria (for B-cell lymphoma). |
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) : iBOR
Časové okno: 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.
|
Immune best overall response(iBOR) To evaluate efficacy of IMC-002 in combination with standard of care (SOC) anti-cancer therapy, as assessed by iRECIST(Solid tumor) or Lugano criteria with LYRIC modification(B-cell Lymphoma). |
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) : iORR
Časové okno: 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.
|
Immune objective response rate(iORR) To evaluate efficacy of IMC-002 in combination with standard of care (SOC) anti-cancer therapy, as assessed by iRECIST(Solid tumor) or Lugano criteria with LYRIC modification(B-cell Lymphoma). |
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) : iDCR
Časové okno: 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.
|
Immune disease control rate(iDCR) To evaluate efficacy of IMC-002 in combination with standard of care (SOC) anti-cancer therapy, as assessed by iRECIST(Solid tumor) or Lugano criteria with LYRIC modification(B-cell Lymphoma). |
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) : iDOR
Časové okno: 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.
|
Immune duration of response(iDOR) To evaluate efficacy of IMC-002 in combination with standard of care (SOC) anti-cancer therapy, as assessed by iRECIST(Solid tumor) or Lugano criteria with LYRIC modification(B-cell Lymphoma). |
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) : iTTP
Časové okno: 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.
|
Immune time-to-progression(iTTP) To evaluate efficacy of IMC-002 in combination with standard of care (SOC) anti-cancer therapy, as assessed by iRECIST(Solid tumor) or Lugano criteria with LYRIC modification(B-cell Lymphoma). |
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) : iPFS
Časové okno: 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.
|
Immune progression-free survival(iPFS) To evaluate efficacy of IMC-002 in combination with standard of care (SOC) anti-cancer therapy, as assessed by iRECIST(Solid tumor) or Lugano criteria with LYRIC modification(B-cell Lymphoma). |
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) : overall survival (OS)
Časové okno: through study completion, an average of 1 year
|
overall survival (OS) |
through study completion, an average of 1 year
|
Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Ředitel studie: HEUNG TAE KIM, MD, ImmuneOncia Therapeutics Inc.
Publikace a užitečné odkazy
Obecné publikace
- 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.
- 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.
- 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.
- 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.
- J.H. Hong, et al. Phase 1b dose-expansion study of IMC-002, a anti-CD47 monoclonal antibody, in patients with advanced triple negative breast cancer (TNBC). ASCO; 2026; Chicago, IL, USA, Abstract 2524.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
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