Immunome to Present Promising Initial Phase 1 Clinical Results for ROR1-Targeted ADC IM-1021 in Advanced B-Cell Lymphomas at ASH 2026
Immunome, Inc., a clinical-stage targeted oncology company focused on developing first-in-class and best-in-class cancer therapies, has announced that it will present initial first-in-human clinical findings from its ongoing Phase 1 study of IM-1021, an investigational ROR1-targeted antibody-drug conjugate (ADC), at the 68th Annual Meeting of the American Society of Hematology (ASH 2026). The investigational therapy is being evaluated as a potential treatment for adults with advanced B-cell lymphomas, a group of blood cancers that includes several aggressive and difficult-to-treat non-Hodgkin lymphoma subtypes.
The upcoming presentation will highlight early clinical activity and safety findings from patients enrolled in the first-in-human Phase 1 study. The initial results indicate that IM-1021 demonstrated antitumor activity across all dose levels evaluated, including in heavily pretreated patients with B-cell non-Hodgkin lymphoma (B-NHL). The findings are particularly noteworthy given the advanced disease status of the study population and the extensive treatment histories of enrolled patients.
According to the initial dataset, 19 patients with B-NHL were evaluable for response. Among these individuals, 10 achieved an objective response, representing an objective response rate (ORR) of 53%. The responses included five complete responses (CRs) and five partial responses (PRs), suggesting that the investigational ADC demonstrated the potential to produce meaningful tumor reductions in patients with advanced disease.
A separate analysis of patients with diffuse large B-cell lymphoma (DLBCL), an aggressive subtype of B-cell non-Hodgkin lymphoma, also showed encouraging early results. Among 11 response-evaluable patients with DLBCL, seven achieved an objective response, resulting in an ORR of 64%. This included three complete responses and four partial responses.
These initial findings provide an early indication of IM-1021’s potential clinical activity across different B-cell lymphoma populations. The observation of responses across all evaluated dose levels also provides important information for the company’s ongoing dose optimization strategy.
Encouraging Clinical Activity in Heavily Pretreated Patients
One of the notable aspects of the initial Phase 1 findings is the level of prior treatment exposure among participants. Patients with B-NHL enrolled in the study had received a median of four previous lines of therapy, reflecting a population with substantial treatment experience and advanced disease.
Treatment options for patients with relapsed or refractory B-cell lymphomas can become increasingly limited following multiple unsuccessful therapies. Although several therapeutic approaches have improved outcomes in certain lymphoma populations, patients whose disease progresses after multiple treatment regimens continue to represent an important unmet medical need.
The initial activity observed with IM-1021 is therefore of interest, particularly because responses were reported among patients who had previously received T-cell redirecting therapies. These therapies, including bispecific antibodies and other immune-based treatment approaches, are designed to direct immune cells toward malignant B cells. However, not all patients respond, and some experience disease progression after initially benefiting from treatment.
The ability to observe clinical responses in this heavily pretreated population may support further investigation of IM-1021 as a potential treatment option for patients with advanced B-cell malignancies.
Commenting on the interim findings, Bob Lechleider, M.D., Chief Medical Officer of Immunome, highlighted the company’s encouragement regarding the observed clinical activity.
“At this interim read, we were encouraged to see clinical activity with IM-1021 in these heavily pretreated patients, including patients whose disease had progressed following T-cell redirecting therapies,” said Dr. Lechleider.
He added that the early findings support the company’s ongoing dose optimization efforts as it continues to advance the investigational therapy and evaluate its potential role in treating B-cell lymphomas.
Dr. Lechleider also emphasized that the Phase 1 study remains ongoing and that the company looks forward to presenting an updated dataset at ASH 2026.
Phase 1 Study Evaluates Safety and Antitumor Activity
The Phase 1 clinical trial is designed to evaluate IM-1021 in adults with advanced B-cell lymphomas, with the initial investigation focused on assessing the therapy’s safety, tolerability, and preliminary antitumor activity.
As of the June 26, 2026, abstract data cutoff, a total of 35 patients had received IM-1021. This included 25 patients with B-cell non-Hodgkin lymphoma.
The safety analysis identified treatment-emergent adverse events (TEAEs) in 92% of patients with B-NHL. Grade 3 or higher treatment-emergent adverse events were reported in 52% of this patient population.
Among the higher-grade adverse events, neutropenia was the most frequently reported, occurring in 44% of patients with B-NHL. Neutropenia is characterized by a reduced number of neutrophils, a type of white blood cell that plays an important role in protecting the body against bacterial and fungal infections.
The incidence of neutropenia is an important safety consideration in oncology drug development, particularly for treatments designed to deliver potent cytotoxic agents to cancer cells. Continued monitoring will help investigators better understand the safety profile of IM-1021, including the frequency, severity, and management of treatment-related toxicities.
The reported safety and efficacy findings represent an early assessment of the investigational therapy. Additional clinical follow-up and enrollment will be important for determining the durability of responses, the consistency of antitumor activity, and the overall benefit-risk profile.
IM-1021 Uses ROR1-Targeted Antibody-Drug Conjugate Technology
IM-1021 is an investigational antibody-drug conjugate designed to target receptor tyrosine kinase-like orphan receptor 1 (ROR1), a cell-surface protein associated with several malignancies, including certain B-cell cancers.
Antibody-drug conjugates are a class of targeted cancer medicines that combine an antibody with a potent cytotoxic payload. The antibody component is designed to recognize and bind a specific protein expressed on cancer cells, while the attached drug payload delivers an anticancer agent to the targeted cells.
This approach aims to improve the selective delivery of cancer-killing agents while potentially limiting exposure to healthy tissues compared with conventional chemotherapy. However, the clinical performance and safety of individual ADCs depend on several factors, including target expression, antibody characteristics, linker stability, payload activity, and drug distribution.
IM-1021 incorporates a topoisomerase I (TOP1) inhibitor payload. TOP1 inhibitors interfere with the activity of topoisomerase I, an enzyme involved in managing DNA structure during essential cellular processes such as DNA replication and transcription.
By disrupting these processes, TOP1 inhibitors can cause DNA damage and ultimately lead to cancer cell death. Linking a TOP1 inhibitor to an antibody that recognizes ROR1 represents an approach intended to deliver the cytotoxic payload to tumor cells expressing the target.
ROR1 is being investigated as a therapeutic target because of its expression in several cancer types. Targeting this protein through an ADC platform may offer an additional strategy for treating malignancies in which ROR1 expression contributes to the identification of cancer cells.
For patients with advanced B-cell lymphomas, an investigational treatment approach that combines targeted delivery with a potent cytotoxic payload could potentially provide another therapeutic option, particularly when established treatment strategies have failed.
The ongoing clinical study will provide further information about the ability of IM-1021 to translate its targeted mechanism into meaningful clinical outcomes.
Dose Optimization Remains a Key Development Priority
Although the initial results demonstrated responses across all evaluated dose levels, Immunome continues to optimize the dosing strategy for IM-1021.
Dose optimization is an important component of early-stage ADC development because the amount of drug administered, treatment frequency, and dosing schedule can influence both antitumor activity and tolerability.
Investigators must identify a dosing regimen that provides sufficient therapeutic exposure to achieve tumor responses while maintaining an acceptable safety profile. This is particularly important for ADCs containing potent cytotoxic payloads, where exposure levels may influence the occurrence and severity of adverse events.
The company is evaluating multiple dosing regimens as part of its ongoing development program. Additional data from the study are expected to help clarify the relationship between dose levels, treatment exposure, clinical responses, and adverse events.
The preliminary findings provide a basis for continued investigation, although the relatively small number of response-evaluable patients means that further data will be necessary to establish the consistency and clinical significance of the observed response rates.
Updated results may also provide additional information about response duration, disease control, and outcomes among patients with different B-cell lymphoma subtypes.
ASH 2026 Presentation to Feature Initial Clinical Findings
Immunome will present the initial first-in-human clinical results for IM-1021 during the 68th American Society of Hematology Annual Meeting. The meeting provides an international platform for researchers, clinicians, pharmaceutical companies, and healthcare professionals to discuss advances in hematology research and the development of new treatments for blood disorders and cancers.
The poster will focus on the clinical evaluation of IM-1021, including its preliminary safety and efficacy findings in adults with advanced B-cell lymphomas.
The presentation is expected to provide additional visibility into the investigational ADC’s early development and the company’s strategy for advancing the treatment through dose optimization.
Presentation Details
- Title: Initial results from first-in-human study of IM-1021, a ROR1-targeted antibody-drug conjugate with TOP1-inhibitor payload, in adults with advanced B-cell lymphomas
- Presenter: Dr. Krish Patel, Sarah Cannon Research Institute
- Session: 629: Aggressive Lymphomas, Non-Cellular Immunotherapy including Bispecific Antibodies: Poster III
- Publication Number: 5457
- Location: MCCNO – Hall F
- Date: December 14, 2026
- Time: 6:00 p.m. – 8:00 p.m.
Advancing Immunome’s Targeted Oncology Pipeline
The IM-1021 program represents part of Immunome’s broader commitment to developing targeted cancer therapies for patients with significant unmet medical needs. The company is focused on identifying and advancing therapeutic candidates that have the potential to deliver differentiated clinical benefits across oncology indications.
The initial Phase 1 results provide an encouraging early signal for IM-1021, particularly given the observed responses in heavily pretreated patients and those who experienced disease progression following T-cell redirecting therapies.
The reported ORR of 53% among response-evaluable patients with B-NHL and 64% among those with DLBCL highlights the investigational treatment’s preliminary antitumor activity. The five complete responses observed in the broader B-NHL response-evaluable population and three complete responses in the DLBCL subgroup further support continued clinical evaluation.
Nevertheless, these findings remain preliminary and should be interpreted in the context of the study’s early stage, limited patient numbers, and ongoing dose optimization.
As the trial progresses, additional clinical evidence will be essential to determine whether the observed responses can be sustained and whether IM-1021 can establish a favorable balance between efficacy and safety.
Immunome plans to continue evaluating multiple dosing regimens and expects to share an updated dataset at ASH 2026. The forthcoming presentation will offer the hematology research community an opportunity to review the early clinical experience with this ROR1-targeted ADC.
With responses reported across evaluated dose levels and preliminary activity observed in patients with advanced and heavily pretreated B-cell lymphomas, IM-1021 remains an investigational candidate of interest in the evolving treatment landscape for B-cell malignancies.
About the IM-1021-101 Trial
The Phase 1 IM-1021-101 study (ClinicalTrials.gov Identifier: NCT06823167) is an ongoing, first-in-human, open-label, multinational, multicenter dose-escalation and expansion study evaluating IM-1021 in patients with advanced B-cell lymphomas and advanced solid tumors. The study is designed to evaluate the safety and tolerability of IM-1021 and select recommended dose(s) for further study, as well as characterize preliminary antitumor activity and pharmacokinetics.
About IM-1021
IM-1021 is an investigational ROR1-targeted ADC currently being evaluated in a Phase 1 study in patients with advanced B-cell lymphomas. ROR1 is expressed in liquid and solid tumors but is largely absent in most mature tissues. IM-1021 incorporates an antibody designed to promote internalization and Immunome’s proprietary TOP1 inhibitor payload, HC74. Immunome designed IM-1021 to optimize ADC-mediated killing of ROR1-positive tumor cells. The company initiated enrollment in the Phase 1 study in the first quarter of 2025.
About Immunome, Inc.
Immunome is a clinical-stage targeted oncology company committed to developing first-in-class and best-in-class cancer therapies. We are advancing an innovative portfolio of therapeutics, supported by a leadership team with deep experience in the design, development, and commercialization of cutting-edge therapies, including antibody-drug conjugates.
Our pipeline includes varegacestat, an investigational, oral, once-daily gamma secretase inhibitor for which an NDA has been accepted by the U.S. FDA; IM-1021, a clinical-stage ROR1 ADC; IM-1617, a clinical-stage solid tumor ADC; IM-3050, a clinical-stage FAP-targeted radiotherapy; and IM-1340, an IND-cleared solid tumor ADC. We are also advancing a broad portfolio of early-stage ADCs pursuing undisclosed solid tumor targets.