HDP-101 Receives FDA Fast Track Designation in Multiple Myeloma

The FDA has granted fast track designation to pamlectabart tismanitin (HDP-101), an investigational antibody drug conjugate (ADC), as a therapy for patients with multiple myeloma, according to a press release from the developer, Heidelberg Pharma.¹

Supporting data for the fast track designation came from nonclinical findings and clinical data from an ongoing phase 1/2a study (NCT04879043). Investigators are currently evaluating the antitumor activity and safety of HDP-101 among patients with relapsed/refractory multiple myeloma as part of this study. Prior findings from this trial were shared at the 2025 European Hematology Association Congress (EHA).²

In cohort 3, in which patients received HDP-101 at 60 µg/kg, stable disease occurred in 1 patient over 17 treatment cycles. Additionally, investigators noted partial responses (PRs) in 2 of 6 patients who received the agent at 100 µg/kg every 3 weeks in cohort 5, with a third patient showing a stringent complete remission (sCR) following 15 months of therapy. Findings from cohort 6, in which investigators administered treatment at 90 µg/kg per cycle in various settings, showed disease progression in 6 of 10 patients. At the time of analysis, 4 patients were still receiving treatment; 2 showed PRs, while an additional 2 had stable disease.

Safety data showed that treatment with HDP-101 appeared to be well-tolerated across different dosing schedules. Most patients in cohort 5 experienced transient grade 2 to 4 thrombocytopenia with a nadir on day 5, which resolved quickly and spontaneously without any clinical symptoms. No patients in cohort 6 experienced grade 4 thrombocytopenia or dose-limiting toxicities.

A safety review committee advised the continuation of dosing in arm B—in which HDP-101 was given at 30 µg/kg on days 1, 8, and 15—as well as arm C—where dosing occurred at 45 µg/kg on days 1 and 8 followed by 90 µg/kg on day 15—with premedication recommended for the first dose in arm C only. Additionally, investigators observed no ocular toxicity associated with HDP-101 at the time of analysis.

“The novel BCMA-targeting ADC HDP-101 shows promising results in heavily pretreated [patients with relapsed/refractory multiple myeloma]. These results support the continuation and further optimization of dosing strategies during the phase 1/2a clinical trial,” lead study author Shambavi Richard, MD, associate professor of Medicine (Hematology and Medical Oncology) with the Center of Excellence for Multiple Myeloma at Mount Sinai, wrote in the abstract with coauthors.²

Developers engineered HDP-101 as a novel ADC that uses a synthetic amanitin payload to target BCMA.

As of February 26, 2025, the first-in-human, open-label, phase 1/2a trial enrolled 34 patients across 7 consecutive dose cohorts. The median patient age was 69 years (range, 43-82), and the median number of prior treatment lines was 5 (range, 2-15).

The trial’s primary end points were dose-limiting toxicities in part 1 of the study, as well as objective response rate.³ Secondary end points included safety and tolerability, and clinical efficacy based on progression-free survival and overall survival.

Patients 18 years and older with a confirmed diagnosis of multiple myeloma based on International Myeloma Working Group guidelines, a life expectancy of more than 12 weeks, an ECOG performance status of 0 to 2, and prior stem cell transplant or transplant ineligibility were eligible for enrollment on the trial. Those with known central nervous system involvement, plasma cell leukemia, or a history of congestive heart failure were ineligible for study entry.

“The FDA’s granting of fast track designation is fantastic news for Heidelberg Pharma and underscores the potential of HDP-101 for the treatment of [patients who are] severely ill and heavily pretreated,” Professor Andreas Pahl, chief executive officer at Heidelberg Pharma, stated in the press release.¹ “This designation will support our efforts to advance our lead ADC candidate efficiently toward patients with multiple myeloma who continue to [have] significant unmet medical needs.”

References

1. PR: Heidelberg Pharma’s lead ADC candidate HDP-101 granted fast track designation by US FDA for the treatment of multiple myeloma. News release. Heidelberg Pharma AG. October 23, 2025. Accessed October 23, 2025. https://tinyurl.com/3fajrb4n
2. Richard S, Orlowski RZ, Kaufman J, et al. The anti-BCMA antibody-drug conjugate HDP-101 with a novel amanitin payload shows promising data in relapsed/refractory multiple myeloma in a phase 1/2a clinical trial as it advances into cohort 7. Presented at the 2025 European Hematology Association Congress (EHA); June 12-15, 2025; Milan, Italy. Abstract PF749.
3. Study to assess safety of HDP-101 in patients with relapsed refractory multiple myeloma. ClinicalTrials.gov. Updated July 24, 2024. Accessed October 23, 2025. https://tinyurl.com/3chzmacm