Phase 1 Study of IMC-002, a Next-Generation Anti-CD47 Antibody, in Advanced Solid Tumors

Jin Seok Ahn; Jung Yong Hong; Joon Oh Park; Sung Young Lee; SuYeon Kim; Hwi-yeol Yun; Chan-Young Ock; Woochan Hwang; Sung Ho Kim; Heung Tae Kim; Ho Yeong Lim

doi:10.4143/crt.2025.820

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Original Article Phase 1 Study of IMC-002, a Next-Generation Anti-CD47 Antibody, in Advanced Solid Tumors: Jin Seok Ahn¹, Jung Yong Hong¹, Joon Oh Park¹, Sung Young Lee², SuYeon Kim², Hwi-yeol Yun³, Chan-Young Ock⁴, Woochan Hwang⁴, Sung Ho Kim², Heung Tae Kim², Ho Yeong Lim¹; DOI: https://doi.org/10.4143/crt.2025.820
Published online: November 4, 2025

¹Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

²ImmuneOncia Therapeutics Inc., Seoul, Korea

³College of Pharmacy, Chungnam National University, Daejeon, Korea

⁴Lunit Inc., Seoul, Korea

Correspondence: Ho Yeong Lim, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
Tel: 82-2-3410-0295 E-mail: hoylim@skku.edu

• Received: August 4, 2025 • Accepted: November 3, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract

Purpose
IMC-002 is a fully human cluster of differentiation 47-targeted immunoglobulin G4 monoclonal antibody, designed to minimize off-target effects. This study (NCT05276310) assessed its safety/tolerability and preliminary anti-tumor activity in patients with advanced solid tumors who were not eligible for or had progressed on standard treatment.
Materials and Methods
We report results from the initial 3+3 design dose-escalation part of a two-part phase 1, open-label, dose-escalation/expansion study. IMC-002 was administered intravenously every 2 weeks at four doses (5, 10, 20, and 30 mg/kg). The primary objective was to assess safety/tolerability, including maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Secondary objectives included pharmacokinetics and clinical activity, including best overall response (BOR), disease control rate (DCR), and clinical benefit rate (CBR).
Results
Twelve patients were included in total, with three per dose level. Most patients (11/12) had stage IV disease; 7/12 had received three prior systemic therapies. No dose-limiting toxicities were observed and MTD was not reached. The most common treatment-related adverse events were rash (9/12), vitreous floaters (8/12), and (hemolytic) anemia (5/12). There was no treatment-related thrombocytopenia, neutropenia, or infection. IMC-002 had dose-proportional pharmacokinetics, achieving steady state levels from cycle 2. BOR was stable disease in six patients (DCR 50.0%). CBR was 33% (four patients maintaining disease control for ≥ 6 months).
Conclusion
IMC-002 demonstrated favorable safety/tolerability at doses of 5-30 mg/kg every 2 weeks. RP2D was defined as 20 mg/kg every 3 weeks. Preliminary anti-tumor activity was observed, with a CBR of 33%.
Key words: CD47, Immunotherapy, Maximum tolerated dose, Monoclonal antibody, Phase I clinical trial, Safety

Introduction

Patients with advanced solid tumors who progress after, or are ineligible for, standard treatment, have poor outcomes and limited treatment options [1-3]. Immunotherapies, such as monoclonal antibodies, have been explored to try to improve disease control in these patients [2].

CD47 is a ubiquitously expressed transmembrane protein that emits a “don’t eat me” signal when it binds to the signal regulatory protein alpha (SIRPα) on phagocytes [4]. Many malignant cells, including those comprising solid tumors, overexpress CD47, thereby inhibiting their phagocytosis. Immunotherapy blockade, as monotherapy or combination therapy, of this CD47-SIRPα interaction overcomes this inhibition and promotes anti-tumor activity in animal models [4-7].

Several CD47/SIRPα targeting agents are in development [8], including human IgG4 anti‑CD47 monoclonal antibodies. Magrolimab (Hu5F9-G4) and lemzoparlimab (TJC4) have demonstrated acceptable tolerability as monotherapies in patients with a variety of malignancies [9,10], and as combination therapy [11] in their respective phase 1 studies. However, as CD47 is widely expressed, anti-CD47 antibodies can cause off-tumor effects—notably, the induction of phagocytosis of CD47-expressing red blood cells, causing anemia and hemagglutination [9,11], which may lead to hemolysis and arterial thrombotic events [12]. Thus, novel approaches to CD47 targeting that minimize the potential for such effects should be explored.

IMC-002 is a fully human IgG4 monoclonal antibody targeting human CD47 [13], and has been optimized for therapeutic efficacy and safety through cell binding affinity-based screening. It contains a hinge-stabilizing S228P mutation to prevent Fab arm exchange [13], as this can cause adverse effects from off-target antigen binding and affect antibody pharmacokinetics and efficacy [14]. Preclinical in vitro studies demonstrated strong binding of IMC-002 to CD47-expressing solid tumors and hematologic cancer cells, but no binding to red blood cells, or hemagglutination [13]. IMC-002 stimulated in vitro phagocytosis of cancer cells by human macrophages and strongly suppressed tumor growth in a dose-dependent manner in xenograft animal models [13]. In murine models of triple-negative breast cancer and hepatocellular carcinoma, IMC-002 exhibited dose-dependent anti-tumor activity [15]. The pharmacokinetic profile was as expected for a therapeutic antibody, and acceptable tolerability was observed in cynomolgus monkeys at doses up to 100 mg/kg [13]. In a first-in-human study of IMC-002 (IMC-002-101) in 12 patients with metastatic or locally advanced solid tumors, IMC-002 was well tolerated when administered weekly or every 2 weeks, and there was no dose-limiting toxicity (DLT) at a dose of 3 mg/kg every 2 weeks (unpublished observations).

Based on these preclinical and clinical observations, the phase 1 IMC‑002-K102 study was designed to further assess the safety and tolerability of IMC-002, determine the recommended phase 2 dose (RP2D), and evaluate pharmacokinetics, preliminary efficacy, and biomarker data. The study consists of two parts: dose-escalation in patients with metastatic or locally advanced solid tumors, followed by dose-expansion, which also includes patients with relapsed or refractory lymphomas. Here, we report data from the dose-escalation part of the IMC-002-K102 study in patients with advanced solid tumors.

Materials and Methods

1. Patients

Patients were aged ≥ 19 years with histologically or cytologically proven metastatic or locally advanced solid tumors who were ineligible for standard treatment or in whom tumors had progressed following standard treatment. Patients were required to have at least one measurable lesion as evaluated by Response Evaluation Criteria in Solid Tumors ver. 1.1 (RECIST 1.1). Full inclusion/exclusion criteria are listed in the Supplementary Methods.

2. Study design and treatment

This is an ongoing phase 1, open-label, dose-escalation and expansion study of the safety, tolerability, pharmacokinetics, and clinical activity of IMC-002 in patients with advanced solid tumors ineligible for standard treatment, or whose tumors had progressed with standard treatment. The primary objective was to evaluate the safety and tolerability of IMC-002, including the maximum tolerated dose (MTD) and RP2D. Secondary objectives included evaluation of pharmacokinetics and preliminary clinical activity. The exploratory objective was to assess potential prognostic biomarkers. Patients were enrolled in the dose-escalation part of the study at a single center in the Republic of Korea (Samsung Medical Center IRB No. 2022-01-161).

The dose-escalation part of the study followed a standard 3+3 design as summarized in S1A Fig. and described in detail in the Supplementary Methods. IMC-002 was administered once every 2 weeks (14-day cycles) as an intravenous infusion over 3 hours (±30 minutes) until disease progression, unacceptable toxicity, or any other withdrawal criterion was met (criteria for study drug discontinuation and study withdrawal are described in detail in the Supplementary Methods). The four planned IMC-002 dose levels (5, 10, 20, and 30 mg/kg) were selected based on evaluation of toxicology data, in vivo efficacy in oncology animal models, and modeled human pharmacokinetic profiles. DLTs were defined as grade ≥ 3 adverse drug reactions (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] ver. 5.0) that occurred during the DLT evaluation period and were confirmed as study treatment-related by the Safety Monitoring Committee, excluding selected event types, as listed in the Supplementary Methods. MTD was considered exceeded if more than one patient in a specific dose cohort experienced DLT. RP2D was determined by the sponsor and Safety Monitoring Committee based on safety and pharmacokinetic data.

3. Safety evaluations

Safety assessments included physical examinations, vital signs, clinical safety laboratory tests, red blood cell phenotyping and direct antiglobulin tests, electrocardiograms, and retinal photographs. Infusion-related reactions were monitored during each IMC-002 infusion and for a minimum of 2 hours afterwards. Adverse events (AEs) were reported by the patients, graded according to the NCI-CTCAE ver. 5.0 and coded using the Medical Dictionary for Regulatory Activities (MedDRA ver. 27.0). AEs were monitored until the 90-day safety follow-up visit, or the start of new cancer treatment, whichever occurred first.

4. Pharmacokinetic evaluations

Blood samples for pharmacokinetic analysis were collected pre-dose and at the end of infusion for all cycles, plus various other timepoints during cycle 1. Samples were analyzed using an enzyme-linked immunosorbent assay, with a lower limit of quantification of 40 ng/mL. Pharmacokinetic parameter calculations were based on actual sampling times and non-compartmental analysis methods. Steady state during multiple dosing was determined based on individual trough serum concentration obtained from at least three time points and a statistical significance test (using an ANOVA method). Pharmacokinetic parameter calculations were performed with Phoenix WinNonlin ver. 8.4 (Certara). Population pharmacokinetic modeling and simulation was performed to identify an appropriate dose to achieve the minimum efficacious concentration (MEC), defined as 24 μg/mL (based on a prior preclinical efficacy study [unpublished observations]), as described in detail in the Supplementary Methods.

5. Efficacy evaluations

Tumor response was assessed by computed tomography scan or magnetic resonance imaging according to RECIST 1.1 and immune RECIST (iRECIST) within 28 days prior to cycle 1 day 1 and every 6 weeks during the treatment period. Best overall response (BOR) was based on tumor assessment during the treatment period. Criteria for complete response (CR), partial response (PR), and stable disease (SD) must have been met at least once after start of study treatment for ≥ 6 weeks from the first dose of study drug to be included in the BOR analysis. Clinical benefit rate was defined as a response of CR or PR, or SD lasting for ≥ 6 months. Disease control rate (DCR) was defined as the proportion of patients with a BOR of CR, PR, or SD.

Follow-up duration was defined as the interval between the date of the first dose and the date of the last available information on survival status. Time to treatment failure was defined as the interval between the date of the first dose and the date of the last dose. Overall survival (OS) was defined as the interval between the date of the first dose and the date of death due to any cause. Patients alive at the time of data analysis or study completion are censored at the date when the patient is last known to be alive.

6. Biomarker evaluations

Biomarker evaluations included assessment of tumor CD47 expression as a potential biomarker for response, using tumor biopsy tissue samples collected prior to study drug administration. Whole slide images of immunohistochemical staining were analyzed using an artificial intelligence-powered analyzer (Lunit SCOPE, Lunit), following methods previously described [16,17] (see Supplementary Methods for details). The density of CD47-positive cells (tumor cells and macrophages) was calculated as the number of positive cells per unit of cancer area, which was identified by the Lunit SCOPE under the supervision of a board-certified pathologist.

7. Statistical analyses

The sample size for the dose-escalation part of the study was not based on any statistical assumptions, as it followed the well-established 3+3 design. All analyses were conducted within the DLT analysis set, which included all patients who received at least one dose of IMC-002 and who had, during the DLT evaluation period, either experienced a DLT or had completed all required safety assessments without experiencing a DLT. Statistical analyses were carried out using SAS software ver. 9.4 or later (SAS Institute Inc.). Descriptive statistics were used for all analyses, unless described otherwise. Time-to-event data were summarized using the median time and 95% confidence intervals (CIs) on the median calculated using Kaplan-Meier estimation.

Results

1. Patients

A total of 12 patients were enrolled in the dose-escalation part of the study, with three patients at each dose level (S1B Fig.). The first patient was enrolled on June 02, 2022. The data cutoff date for the present analysis was January 10, 2025, after a median follow-up duration of 17.7 months (95% CI, 3.2 to 28.1).

Baseline demographics and characteristics are reported in Table 1. Median age was 57 years (range, 48 to 73 years). Most patients had stage IV cancer (11/12 [92%]) and distant metastases (11/12 [92%]) at multiple sites (10/12 [83%]), and the median number of prior systemic therapies was three (range, 1 to 3). Patients received a median of six cycles of study drug doses (range, 3 to 32).

2. Safety

No DLTs were observed at any IMC-002 dose levels. Treatment-emergent AEs (TEAEs) and treatment-related AEs (TRAEs) were reported in all 12 patients, with the majority (94%) occurring during the first treatment cycle. Hematologic toxicities observed in this study included hemolytic anemia (4/12 patients [33%]) and anemia (1/12 [8%]). Hemolytic anemia and anemia were mostly resolved following cycle 1. No cases of thrombocytopenia or neutropenia were observed. Among non-hematologic toxicities, the most frequently reported events were rash (9/12 [75%]) and vitreous floaters (8/12 [67%]). All of these events were considered treatment-related (Table 2). Both rash and vitreous floaters occurred on the day of the first infusion or within a few days thereafter; rash events were grade 1 or 2, and vitreous floaters were grade 1, none of which interfered with daily activities. Grade 3 TEAEs were reported in four patients (33%), including hemolytic anemia in three patients, and one case each of increased blood bilirubin, hypocalcemia, and neck pain; only the hemolytic anemia events were considered treatment-related (one patient in 20 mg/kg cohort and two patients in 30 mg/kg cohort), and no grade 4 or 5 TEAEs occurred. No patients discontinued treatment or required dose reductions due to TRAEs. Two patients experienced TRAEs that led to temporary dose interruptions: one patient had grade 2 rash, grade 1 non-cardiac chest pain, and grade 1 headache on the first dosing day, resulting in a brief interruption followed by resumption after recovery; another patient experienced grade 3 hemolytic anemia, which delayed subsequent dosing schedule, with treatment resumed thereafter.

Four serious TEAEs were reported in three patients (25%): liver function test increased in one patient (30 mg/kg cohort), pyrexia in one patient (20 mg/kg cohort), and spinal cord compression and postoperative wound infection in one patient (30 mg/kg cohort). Only one serious TEAE considered treatment-related, liver function test increased, was observed in a patient with hepatocellular carcinoma involving multiple organs including the lungs and spleen. Clinically significant abnormalities associated with this event included elevations in alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin. This event was most likely attributable to the patient’s underlying disease and medical history of hepatitis B virus infection. Notably, the patient had received only a single dose of the study drug before the onset of the event, and no recurrence of the event was observed after treatment was resumed, continuing through cycle 10.

At all doses, there was a decrease in hemoglobin levels after initial exposure, which generally subsequently recovered (Fig. 1A). Recovery in hemoglobin levels was delayed for patients who received the 30 mg/kg dose compared with the other dose levels, with mean hemoglobin levels decreasing to a grade 2 anemia level before recovering. In all dose cohorts, mean neutrophil and platelet counts were maintained throughout the study, with no decreases to the level of grade 1 or worse neutropenia or thrombocytopenia after the first treatment cycle (Fig. 1B and C).

3. Pharmacokinetics

A dose-dependent increase in serum exposure was observed for IMC-002 (Fig. 2A). For all doses, the serum concentration decreased over time following the initial dose (Fig. 2A, S2 Fig.). Steady state during multiple dosing was observed from cycle 2 onwards (Fig. 2B, S3 Table).

The final model adopted for pharmacokinetic modeling and simulation was a target-mediated drug disposition model, including neonatal Fc receptor recycling of IgG, as it adequately described the pharmacokinetics of IMC-002 (S4 Fig.). No covariates were identified that had a clinically relevant effect on IMC-002 pharmacokinetics. In the final simulation model, predicted trough concentrations of IMC-002 at steady state exceeded the MEC (24 μg/mL) when administered as 20 mg/kg or 30 mg/kg intravenous infusions every 3 weeks (Fig. 2B, S2 Fig., S5 Table).

4. Efficacy

Among the 12 patients (all of whom were evaluable for efficacy), BOR was SD in six patients (DCR, 50.0%). Clinical benefit rate was 33% (four patients) (Fig. 3A). Analysis of best percentage change from baseline in target lesion size is presented in Fig. 3B.

The median time to treatment failure was 3 months (95% CI, 2 to 18). At the time of analysis, eight patients had died after a median OS of 17.6 months (95% CI, 5.23 to 19.01). One- and 2-year survival rates were 66.7% (8/12 patients) and 33.3% (4/12 patients), respectively (S6 Fig.).

The most common subsequent therapy was the programmed cell death protein 1 (PD-1)–targeting antibody nivolumab, received by 5/12 patients (42%) (S7 Table).

5. Biomarkers

The mean density of CD47-positive macrophages was numerically higher in patients who experienced clinical benefit compared with those who did not (71.0 vs. 44.3 cells/mm², respectively) (S8 Table). The mean density of CD47-positive tumor cells was similar in patients with and without a clinical benefit (3,289.3 vs. 4,098.4 cells/mm², respectively) (S8 Table). Representative CD47 immunohistochemistry images in clinical benefit and non-clinical benefit cases are shown in S9 Fig.

Discussion

This phase 1 dose-escalation study evaluated the fully human IgG4 antibody IMC-002 in patients with locally advanced or metastatic solid tumors who were not eligible for standard treatment, or whose tumors progressed following standard treatment. IMC-002 demonstrated an acceptable safety and tolerability profile when administered intravenously at doses of up to 30 mg/kg every 2 weeks. No DLTs were recorded during the 21-day evaluation period; MTD was therefore not reached. RP2D, based on the available safety and pharmacokinetic results, was determined as 20 mg/kg IMC-002 administered every 3 weeks.

Preliminary analyses from this study highlight promising anti-tumor activity of IMC-002, with one-third of patients maintaining disease control for over 6 months. These data are indicative of a potentially durable anti-tumor effect, despite most patients having received third-line therapy and one-third receiving prior PD-1 or programmed death ligand 1 (PD-L1) inhibitor therapy.

Immunotherapy helps to overcome the unfavorable safety profiles and off-target toxicity often associated with cytotoxic therapies [2]. The safety profile of IMC-002 in the current study was favorable and as expected for the patient population, many of whom had heavily pretreated stage IV advanced tumors and multiple distant metastases. Most TEAEs and TRAEs in this study were grade 1 or 2. The observed safety and tolerability results were also favorable and as expected, in comparison with other anti-CD47 antibodies, with respect to off-target-associated AEs, such as anemia. In the first-in-human phase 1 study of magrolimab (monotherapy), anemia was observed in 57% of patients, despite the use of priming doses intended to mitigate it [9]. Magrolimab combination therapy, with rituximab or azacitidine, resulted in 34%-41% anemia incidence [11,18,19]. Anemia was grade 3 in approximately half of cases in the rituximab combination study; all anemia events were grade 3 or 4 in the azacitidine study [11,18,19]. In contrast, in the present study, hemolytic anemia or anemia occurred in 42% of patients and was grade 3 in only 25% of patients, despite no priming dose being administered. Similarly, no priming dose was used in the first-in-human study of lemzoparlimab, another fully human CD47-targeted IgG4 antibody, in which anemia was reported in 30% of patients [10].

IMC-002 displayed dose-proportional pharmacokinetics, with steady-state levels observed from cycle 2 onwards. In the body, IgG has a longer half-life than other immunoglobulins due to the recycling function of the neonatal fragment crystallizable receptor (FcRN), which salvages monomeric IgG and protects it from intracellular degradation [20]. Thus, a mechanism-based target-mediated drug disposition model was selected as the final model in the current analysis. It is unsurprising that no statistically significant covariates were identified in this study because IMC-002 was administered at a weight-based dose and the tested covariates (e.g., age and sex) may correlate with weight. Based on the simulation results from the final model, IMC-002 administered at either 20 mg/kg or 30 mg/kg every 3 weeks resulted in predicted trough levels exceeding the MEC. Furthermore, the half-life of IMC‑002 should provide consistent systemic exposure levels over a 3-weekly cycle, without drug accumulation. The 20 mg/kg every-3-weeks dosing regimen of IMC-002 was selected as the RP2D for subsequent studies, including the dose-expansion part of this study, as it may allow alignment with commonly used chemotherapy regimens.

Preliminary biomarker analyses revealed a numerically higher mean density of CD47-positive macrophages in patients with clinical response to IMC-002. However, the heterogeneity of tissue sample sites (primary vs. metastatic) and timing of sampling could have impacted these results, as seen previously for PD-L1 expression [21]. This result should therefore be interpreted with caution, highlighting the need to standardize spatiotemporal factors in future analyses exploring CD47-positivity as a biomarker for response to IMC-002.

Progression following standard treatment for advanced or metastatic solid tumors is associated with poor outcomes [3], and second-line standard-of-care treatments are particularly lacking for patients with hepatocellular carcinoma, biliary tract cancer, and triple-negative breast cancer [1,22]. IMC-002 demonstrated preliminary anti-tumor activity in heavily pretreated patients with related malignancies, as 50% of patients achieved a BOR of SD and 33% achieved clinical benefit. Phase 1 dose-escalation studies of other anti-CD47 antibodies as monotherapy have demonstrated anti-tumor activity in patients with relapsed/refractory or advanced solid tumors [9,10]. In a phase 1 study of magrolimab as monotherapy, two patients (3%) achieved PR, and one (with diffuse large B-cell lymphoma) achieved a mixed response to therapy [9]. Additionally, in phase 1b/2 combination therapy studies of magrolimab in hematologic malignancies, objective response rates of 47%-52% have been achieved, with CR rates of 30%-36% [11,18,19]. These higher response rates are expected for combination treatment approaches in heterogeneous groups of patients, some of whom had received no previous systemic treatment. However, despite these encouraging results, several magrolimab trials have been discontinued due to safety and efficacy concerns [23].

Other monotherapy and combination approaches to targeting CD47 are also being explored. Fusion proteins targeting the CD47/SIRPα pathway, a key pathway in phagocytosis, have shown promising anti-tumor activity as monotherapy [24,25] or combination therapy (e.g., NCT03013218, NCT04675294, NCT04675333). Further investigation of fusion protein/PD-1 inhibitor combination therapy is planned [26]. However, safety concerns have been raised for some of these compounds, and several phase 1 and 2 studies such as NCT04485065, NCT04485052, and NCT04511975 have been discontinued accordingly [23,27].

Due to its promising anti-tumor activity and tolerability, IMC-002 has potential to be combined with other anticancer treatments, such as chemotherapy or other immunotherapies, to enhance current standard-of-care for patients with solid tumors, without adding to the hematologic toxicity burden, and may also have synergistic effects. CD47 and PD-L1 act as important innate and adaptive checkpoints, which work together to help cancer cells evade the immune response [4]. Preclinical studies have shown that dual blockade of these checkpoints improves tumor targeting and enhances efficacy, compared with either agent alone [4,7]. It is noteworthy that the most common subsequent therapy in the present study was nivolumab, which targets PD-1. Subsequent therapy with nivolumab, anti–cytotoxic T lymphocyte antigen-4 antibodies, vascular endothelial growth factor receptor 2–targeting antibodies, tyrosine kinase inhibitors, and chemotherapy drugs, extended the median OS to 17.6 months after a median time to treatment failure of 3 months with IMC-002. Further studies are warranted into the most beneficial sequencing and combination of these drugs with differing mechanisms of action.

There are some constraints to the current study. Similar to other phase 1 studies, patients with various tumor types and treatment histories were eligible to broadly assess safety and preliminary activity. Although enrollment was not restricted to any tumor types, most patients (about 75%) had advanced HCC, reflecting site-specific patient availability rather than pre-specified selection. This predominance of HCC may limit the generalization of the findings across tumor types. The ongoing dose-expansion part of the study includes a dedicated HCC cohort, which will allow for a more robust evaluation in this population, along with additional cohorts in other solid tumors and lymphomas to address broader applicability.

In conclusion, IMC-002 demonstrated an acceptable safety profile and dose-proportional pharmacokinetics when administered intravenously every 2 weeks at doses up to 30 mg/kg in patients with locally advanced or metastatic solid tumors who had progressed after standard therapy. Preliminary anti-tumor activity was observed, with 33% of patients achieving durable disease control. Based on the safety data and pharmacokinetic analysis, a dose of 20 mg/kg every 3 weeks was selected as the RP2D for further clinical development.

Electronic Supplementary Material

Supplementary materials are available at Cancer Research and Treatment website (https://www.e-crt.org).

crt-2025-820_S1_Fig.pdf

crt-2025-820_S2_Fig.pdf

crt-2025-820_S3_Table.pdf

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crt-2025-820_S5_Table.pdf

crt-2025-820_S6_Fig.pdf

crt-2025-820_S7_Table.pdf

crt-2025-820_S8_Table.pdf

crt-2025-820_S9_Fig.pdf

crt-2025-820_Supplementary_Methods.pdf

NOTES

Ethical Statement

The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines and is registered at ClinicalTrials.gov (NCT05276310), and was approved by the institutional review board at the participating institution (Samsung Medical Center IRB No. 2022-01-161). Informed consent was obtained from all individual participants in the study.

Author Contributions

Conceived and designed the analysis: Ahn JS, Hong JY, Park JO, Lee SY, Kim S, Yun H, Ock CY, Hwang W, Kim SH, Kim HT, Lim HY.

Collected the data: Ahn JS, Hong JY, Park JO, Lim HY.

Contributed data or analysis tools: Ahn JS, Hong JY, Park JO, Lee SY, Kim S, Yun H, Ock CY, Hwang W, Kim SH, Kim HT, Lim HY.

Performed the analysis: Ahn JS, Hong JY, Park JO, Lee SY, Kim S, Yun H, Ock CY, Hwang W, Kim SH, Kim HT, Lim HY.

Wrote the paper: Ahn JS, Hong JY, Park JO, Lee SY, Kim S, Yun H, Ock CY, Hwang W, Kim SH, Kim HT, Lim HY.

Conflicts of Interest

J.S. Ahn reports payment or honoraria for lectures, presentations, speaker bureau, manuscript writing, or educational events from Nokwon Medical, Boryung, Yuhan, Takeda Pharmaceuticals, Samyang Biopharm, Pfizer, Boehringer Ingelheim, Bayer Korea, Menarini Korea, BC World Pharmaceuticals, Roche Korea, AstraZeneca Korea, Novartis Korea, Amgen Korea, Lilly Korea, Kyowa Kirin, LG Chem, and Daiichi Sankyo Korea. J.S. Ahn also reports participation on a Data Safety Monitoring Board or Advisory Board for Daiichi Sankyo Korea, ImmuneOncia Therapeutics, Inc., Therapex, Pfizer, Pharmbio Korea, Roche Korea, Yuhan, and Guardant Health. CY. Ock reports stock and stock options from Lunit. HY. Yun reports no conflicts of interest. J.Y. Hong reports payment or honoraria for presentations from Roche, AstraZeneca, and Eisai; participation on a Data Safety Monitoring Board or Advisory Board for MedPacto and ImmuneOncia Therapeutics Inc.; and stock/stock options from Moderna, Guardant Health, and GRAIL. S.Y. Lee, S.H. Kim, and H.T. Kim report stock options from and being an employee of ImmuneOncia Therapeutics, Inc. S.Y. Kim reports being an employee of ImmuneOncia Therapeutics, Inc. W. Hwang reports being an employee of Lunit. H.Y. Lim reports an Advisory Board role for Eisai, Roche, AstraZeneca, Bayer, Bristol Myers Squibb, Ono, and MSD; and participation on a Data Safety Monitoring Board or Advisory Board for ImmuneOncia Therapeutics, Inc., J.O. Park contributed patients to the study and reports provision of study materials and medical writing support in relation to the present manuscript; and grants from Servier, BMS (Celgene), ABL Bio, Eutilex and MedPacto; consulting fees from ImmuneOncia, Intocell, AstraZeneca and Merck Serono; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Minnemarita; support for attending advisory boards from Arcus Biosciences, Adecet Bio, and MediRama; and participation on a Data Safety Monitoring Board or Advisory Board for ImmuneOncia Therapeutics, Inc., all unrelated to the present manuscript.

Funding

This study was funded by ImmuneOncia Therapeutics Inc. (Seoul; Korea), who played a role in the study design, data collection and analysis, decision to publish, and preparation of the manuscript.

Acknowledgments

We thank all patients and investigators involved in the study. Medical writing support, including development of a draft outline and subsequent drafts in consultation with the authors, collating author comments, copyediting, fact checking, and referencing, was provided by Caroline Greenwood and Dawn Batty at Aspire Scientific Limited (Bollington, UK). Funding for this study and medical writing support for this article was provided by ImmuneOncia Therapeutics Inc. (Seoul, Korea). Preliminary results of this study were presented in a poster at the 2023 meeting of the European Society of Medical Oncology (HY Lim, et al. Phase 1 dose-escalation study of IMC-002, a novel anti-CD47 monoclonal antibody, in patients with advanced solid tumors; poster #1035P) and the 2024 meeting of the American Society of Clinical Oncology (HY 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; poster #2642).

Fig. 1.

Hemoglobin (A), neutrophil (B), and platelet (C) levels across IMC-002 dose cohorts and visits. C, cycle; D, day.

Fig. 2.

Mean serum concentrations of IMC-002 following initial dose (A) and simulated serum concentrations of IMC-002 over time with intravenous infusion every 3 weeks (B).

Fig. 3.

Tumor response over time (A) and best percentage change from baseline in target lesion size (B). iCPD, immune confirmed progressive disease; iUPD, immune unconfirmed progressive disease; PR, partial response; Q2W, every 2 weeks; SD, stable disease. Symbols in (A) indicate start time of indicated tumor response category.

Table 1.

Baseline demographics and characteristics by IMC-002 dose

	5 mg/kg (n=3)	10 mg/kg (n=3)	20 mg/kg (n=3)	30 mg/kg (n=3)	Total (n=12)
Age (yr), median (range)	56 (54-57)	62 (53-73)	53 (52-73)	60 (48-64)	57 (48-73)
Sex
Female	0	2	1	1	4
Male	3	1	2	2	8
Race Asian	3	3	3	3	12
ECOG PS
0	2	3	3	3	11
1	1	0	0	0	1
Primary disease
Hepatocellular carcinoma	3	2	2	2	9
Breast cancer	0	1	0	1	2
Gallbladder cancer	0	0	1	0	1
Tumor stage
III	0	0	1	0	1
IV	3	3	2	3	11
Prior surgery	3	3	2	3	11
Prior radiotherapy	3	1	1	3	8
No. of prior systemic therapies
1	0	2	0	0	2
2	0	1	1	1	3
3	3	0	2	2	7
Prior anti–PD-(L)1 treatment	2	0	1	1	4
Time from prior therapy to start of study drug dose (mo), median (range)	1.0 (0.7-1.0)	1.0 (1.0-1.6)	1.0 (1.0-3.9)	1.5 (1.3-1.5)	1.0 (0.7-3.9)

Unless otherwise specified, values represent number of patients. ECOG PS, Eastern Cooperative Oncology Group performance status; PD-(L)1, programmed cell death-(ligand) 1.

Table 2.

TRAEs by MedDRA preferred term across IMC-002 dose cohorts

Category TRAEs	5 mg/kg (n=3)	10 mg/kg (n=3)	20 mg/kg (n=3)	30 mg/kg (n=3)	Total (n=12), n (%)
Category TRAEs	5 mg/kg (n=3)	10 mg/kg (n=3)	20 mg/kg (n=3)	30 mg/kg (n=3)	All grades^a)	Grade 3
Hematologic toxicity
Hemolytic anemia	0	0	2	2	4 (33.3)	3 (25.0)
Anemia	0	0	0	1	1 (8.3)	0
Non-hematologic toxicity
Rash	2	3	2	2	9 (75.0)	0
Vitreous floaters	3	3	0	2	8 (66.7)	0
Headache	1	1	0	0	2 (16.7)	0
Myalgia	0	0	2	0	2 (16.7)	0
Nausea	1	0	1	0	2 (16.7)	0
Decreased appetite	0	1	0	0	1 (8.3)	0
Diarrhea	0	0	0	1	1 (8.3)	0
Fatigue	0	0	0	1	1 (8.3)	0
LFT increased	0	0	0	1	1 (8.3)	0
Non-cardiac chest pain	1	0	0	0	1 (8.3)	0
Pruritus	0	1	0	0	1 (8.3)	0
Pyrexia	0	0	0	1	1 (8.3)	0
Vomiting	0	0	1	0	1 (8.3)	0

Unless otherwise specified, values represent number of patients. LFT, liver function test; MedDRA, Medical Dictionary for Regulatory Activities; TRAE, treatment-related adverse event.

^a) Grades 1-3 (there were no grade 4 or 5 TRAEs).

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Phase 1 Study of IMC-002, a Next-Generation Anti-CD47 Antibody, in Advanced Solid Tumors

DOI: https://doi.org/10.4143/crt.2025.820

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Phase 1/2a Study of Rivoceranib, a Selective VEGFR-2 Angiogenesis Inhibitor, in Patients with Advanced Solid Tumors

Phase 1 Study of IMC-002, a Next-Generation Anti-CD47 Antibody, in Advanced Solid Tumors

Fig. 1. Hemoglobin (A), neutrophil (B), and platelet (C) levels across IMC-002 dose cohorts and visits. C, cycle; D, day.

Fig. 2. Mean serum concentrations of IMC-002 following initial dose (A) and simulated serum concentrations of IMC-002 over time with intravenous infusion every 3 weeks (B).

Fig. 3. Tumor response over time (A) and best percentage change from baseline in target lesion size (B). iCPD, immune confirmed progressive disease; iUPD, immune unconfirmed progressive disease; PR, partial response; Q2W, every 2 weeks; SD, stable disease. Symbols in (A) indicate start time of indicated tumor response category.

Fig. 1.

Fig. 2.

Fig. 3.

Phase 1 Study of IMC-002, a Next-Generation Anti-CD47 Antibody, in Advanced Solid Tumors

	5 mg/kg (n=3)	10 mg/kg (n=3)	20 mg/kg (n=3)	30 mg/kg (n=3)	Total (n=12)
Age (yr), median (range)	56 (54-57)	62 (53-73)	53 (52-73)	60 (48-64)	57 (48-73)
Sex
Female	0	2	1	1	4
Male	3	1	2	2	8
Race Asian	3	3	3	3	12
ECOG PS
0	2	3	3	3	11
1	1	0	0	0	1
Primary disease
Hepatocellular carcinoma	3	2	2	2	9
Breast cancer	0	1	0	1	2
Gallbladder cancer	0	0	1	0	1
Tumor stage
III	0	0	1	0	1
IV	3	3	2	3	11
Prior surgery	3	3	2	3	11
Prior radiotherapy	3	1	1	3	8
No. of prior systemic therapies
1	0	2	0	0	2
2	0	1	1	1	3
3	3	0	2	2	7
Prior anti–PD-(L)1 treatment	2	0	1	1	4
Time from prior therapy to start of study drug dose (mo), median (range)	1.0 (0.7-1.0)	1.0 (1.0-1.6)	1.0 (1.0-3.9)	1.5 (1.3-1.5)	1.0 (0.7-3.9)

Category TRAEs	5 mg/kg (n=3)	10 mg/kg (n=3)	20 mg/kg (n=3)	30 mg/kg (n=3)	Total (n=12), n (%)
Category TRAEs	5 mg/kg (n=3)	10 mg/kg (n=3)	20 mg/kg (n=3)	30 mg/kg (n=3)	All grades^a)	Grade 3
Hematologic toxicity
Hemolytic anemia	0	0	2	2	4 (33.3)	3 (25.0)
Anemia	0	0	0	1	1 (8.3)	0
Non-hematologic toxicity
Rash	2	3	2	2	9 (75.0)	0
Vitreous floaters	3	3	0	2	8 (66.7)	0
Headache	1	1	0	0	2 (16.7)	0
Myalgia	0	0	2	0	2 (16.7)	0
Nausea	1	0	1	0	2 (16.7)	0
Decreased appetite	0	1	0	0	1 (8.3)	0
Diarrhea	0	0	0	1	1 (8.3)	0
Fatigue	0	0	0	1	1 (8.3)	0
LFT increased	0	0	0	1	1 (8.3)	0
Non-cardiac chest pain	1	0	0	0	1 (8.3)	0
Pruritus	0	1	0	0	1 (8.3)	0
Pyrexia	0	0	0	1	1 (8.3)	0
Vomiting	0	0	1	0	1 (8.3)	0

Table 1. Baseline demographics and characteristics by IMC-002 dose

Unless otherwise specified, values represent number of patients. ECOG PS, Eastern Cooperative Oncology Group performance status; PD-(L)1, programmed cell death-(ligand) 1.

Table 2. TRAEs by MedDRA preferred term across IMC-002 dose cohorts

Unless otherwise specified, values represent number of patients. LFT, liver function test; MedDRA, Medical Dictionary for Regulatory Activities; TRAE, treatment-related adverse event.

Grades 1-3 (there were no grade 4 or 5 TRAEs).