HDP-101 for Multiple Myeloma

Recruiting at 16 trial locations

Overseen By András Strassz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Heidelberg Pharma AG

Must be taking: Immunomodulatory, Proteasome inhibitors, Anti-CD38

Must not be taking: BCMA-targeting modalities

Disqualifiers: CNS involvement, Plasma cell leukemia, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

78 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called HDP-101, an antibody-drug conjugate, for individuals with multiple myeloma, a type of blood cancer. The main goal is to determine if HDP-101 is safe, how effectively it works in the body, and its potential to treat multiple myeloma. The trial will evaluate different doses to identify the optimal one. Candidates may qualify if they have active multiple myeloma, have previously tried other treatments, and still have measurable disease. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that HDP-101 is likely to be safe for humans?

Research has shown that HDP-101 demonstrates promising safety results in studies with patients who have relapsed or hard-to-treat multiple myeloma. Early findings suggest that patients generally tolerate this treatment well, even those who have tried many other treatments. Some side effects have been reported, but they remain manageable.

HDP-101 targets cancer cells specifically, which may help reduce unwanted effects on healthy cells. This targeted approach is a key reason for its apparent safety. Its FDA Fast Track designation further suggests that early safety data is encouraging. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Unlike the standard treatments for multiple myeloma, such as chemotherapy, immunomodulatory drugs, and proteasome inhibitors, HDP-101 introduces a novel approach by using an antibody-drug conjugate (ADC). This treatment combines a targeted monoclonal antibody with a powerful anti-cancer drug, allowing it to specifically seek out and destroy cancer cells while minimizing damage to healthy cells. Researchers are excited about HDP-101 because it targets B-cell maturation antigen (BCMA), which is highly expressed on multiple myeloma cells, offering the potential for more precise and effective treatment outcomes with fewer side effects.

What evidence suggests that HDP-101 might be an effective treatment for multiple myeloma?

Research has shown that HDP-101, a treatment combining an antibody with a drug, shows promise for patients with multiple myeloma that has returned or not responded to other treatments. HDP-101 targets a protein on myeloma cells and delivers a powerful toxin called amanitin directly to them. This approach has proven very effective in lab tests, especially in cells with certain genetic changes. Early human trials have also shown encouraging results, suggesting that HDP-101 could be a viable option for patients who have tried several other treatments. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed or refractory multiple myeloma who have tried other treatments including immunomodulatory drugs, proteasome inhibitors, and anti-CD38 therapy. They should not be eligible for a stem cell transplant or must have already had one. Participants need to be in relatively stable health (ECOG PS 0-2) and cannot join if they've recently received certain cancer therapies, have active infections like hepatitis B/C or HIV, heart failure, or any other active cancers.

Inclusion Criteria

My organs are functioning well.

I've been treated with specific myeloma drugs and either didn't respond or couldn't tolerate standard treatments.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I have not had radiotherapy in the last 21 days.

I have a history of heart failure.

I have tested positive for hepatitis C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive HDP-101 intravenously in a 21-day cycle to evaluate tolerability and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)

21-day cycles

Dose Expansion

Participants receive HDP-101 at the RP2D to collect preliminary evidence of antitumor activity and confirm safety

21-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HDP-101

Trial Overview The study is testing HDP-101's safety and effectiveness in patients with multiple myeloma. It will look at how the body processes the drug (pharmacokinetics), its tolerability at different doses, and its potential as a treatment option compared to current standards.

How Is the Trial Designed?

Group I: HDP-101 Experimental Treatment 1 Intervention

Participants will receive HDP-101 intravenously in a 21 day cycle until disease progression, intolerable toxicity, Investigator's discretion or patient withdrawal. During the phase 1 tolerability of different dose levels will be evaluated. During the phase 2a dose expansion part the recommended phase 2 dose (RP2D) of HDP-101 will be administered.

Who Is Running the Clinical Trial?

Heidelberg Pharma AG

Lead Sponsor

Trials

10

Recruited

1,500+

Published Research Related to This Trial

Researchers developed monoclonal antibodies (MAbs) targeting unique surface markers of the U266 multiple myeloma cell line, with the best fusion efficiency achieved at an immunogen concentration of 10 microg.

Out of 147 screened supernatants, seven MAbs were identified as specific to myeloma cells, suggesting potential for use in imaging, phenotyping, and targeted therapy for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of monoclonal antibodies to surface proteins of human multiple myeloma employing membrane extracts for murine in vivo immunizations. Ravi, M., Balaji, S., Srinivasan, L., et al.[2009]

The humanized anti-HM1.24 monoclonal antibody (MoAb) shows promising antitumor activity against multiple myeloma by effectively mediating antibody-dependent cellular cytotoxicity (ADCC) with human immune cells, including those from myeloma patients.

ADCC activity can be significantly improved in patients with reduced immune response by using immunomodulating cytokines like IL-2, IL-12, or IL-15, suggesting a potential strategy to enhance the efficacy of the anti-HM1.24 MoAb in treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Humanized anti-HM1.24 antibody mediates myeloma cell cytotoxicity that is enhanced by cytokine stimulation of effector cells. Ozaki, S., Kosaka, M., Wakahara, Y., et al.[2021]

CD26 is expressed on plasma cells in multiple myeloma (MM) patients and its expression increases when MM cells are co-cultured with osteoclasts, making it a potential target for therapy.

The humanized IgG1 monoclonal antibody targeting CD26 (huCD26mAb) enhances antibody-dependent cytotoxicity (ADCC) against CD26+ MM cells and significantly reduces tumor burden and osteoclast formation in vivo, indicating its therapeutic potential in treating MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD26 is a potential therapeutic target by humanized monoclonal antibody for the treatment of multiple myeloma. Nishida, H., Hayashi, M., Morimoto, C., et al.[2019]

Belantamab mafodotin is a newly approved treatment for relapsed or refractory multiple myeloma, showing an overall response rate of 31% and a median progression-free survival of 2.9 months in patients who have undergone at least four prior therapies.

While the treatment is generally well tolerated, it is associated with notable ocular toxicities, which require careful management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Ocular Toxicity in Patients Receiving Belantamab Mafodotin. Lu, R., Morphey, A., Diaz, F., et al.[2023]

Two promising antibody-based therapies for multiple myeloma, IMGN901 and BT062, are currently in clinical development, targeting specific proteins on myeloma cells and linked to potent cytotoxic agents.

IMGN901 targets CD56, found on most myeloma cells, while BT062 targets CD138, a key diagnostic marker, suggesting these therapies could improve treatment outcomes by combining specificity with powerful anti-tumor effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-maytansinoid conjugates for the treatment of myeloma. Lutz, RJ., Whiteman, KR.[2021]

The study presents a scalable method for synthesizing (2S,3R,4R)-4,5-dihydroxyisoleucine (DHIle), a crucial amino acid in α-amanitin, which is important for further research.

This synthesis allows for the creation of an equipotent analogue, Asn(N-ethylazide)-S,6'-dideoxy-α-amanitin, which can be used in therapeutic antibody-drug conjugate studies, enhancing the potential for targeted cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scaling Amatoxin Synthesis with an Improved Route to (2S,3R,4R)-Dihydroxyisoleucine Exemplified by a Toxic, Clickable α-Amanitin Analogue. Hambira, CM., Matinkhoo, K., Pryyma, A., et al.[2021]

SAR442085, a next-generation anti-CD38 monoclonal antibody, demonstrated superior binding affinity and enhanced antibody-dependent cellular cytotoxicity (ADCC) compared to first-generation antibodies like daratumumab and isatuximab in preclinical studies involving multiple myeloma cells.

In vivo studies using transgenic mice showed that SAR442085 resulted in better natural killer (NK) cell activation and improved antitumor efficacy, leading to increased survival rates compared to existing anti-CD38 therapies, supporting its potential for clinical evaluation in patients with relapsed/refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAR442085, a novel anti-CD38 antibody with enhanced antitumor activity against multiple myeloma. Kassem, S., Diallo, BK., El-Murr, N., et al.[2022]

Amanitin-based antibody-drug conjugates (ADCs) utilize a unique mechanism by inhibiting RNA Polymerase II, which represents a novel approach in cancer therapy.

The ADC HDP-101, targeting BCMA, is set to enter clinical trials in 2019, showcasing the potential of amanitin-based ADCs to provide effective treatment with a favorable therapeutic index.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amanitins and their development as a payload for antibody-drug conjugates. Pahl, A., Lutz, C., Hechler, T.[2019]

HDP-101, an antibody-drug conjugate targeting BCMA, effectively inhibits both active and dormant multiple myeloma cells while sparing non-target cells, showing promise in overcoming drug resistance.

In animal models, HDP-101 induced significant tumor regression and durable remissions at low doses, and it was well tolerated in cynomolgus monkeys, indicating a favorable safety profile for potential clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HDP-101, an Anti-BCMA Antibody-Drug Conjugate, Safely Delivers Amanitin to Induce Cell Death in Proliferating and Resting Multiple Myeloma Cells. Figueroa-Vazquez, V., Ko, J., Breunig, C., et al.[2021]

In a study of 102 patients with relapsed and refractory multiple myeloma treated with daratumumab, higher pretreatment levels of CD38 on cancer cells were linked to better treatment responses, indicating that CD38 expression is a key factor in the drug's efficacy.

Changes in the expression of complement-inhibitory proteins (CIPs) like CD55 and CD59 were associated with disease progression, suggesting that therapies aimed at modifying CD38 and CIP levels could enhance the effectiveness of daratumumab and overcome resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Nijhof, IS., Casneuf, T., van Velzen, J., et al.[2022]

α-Amanitin, a potent inhibitor of RNA polymerase II, can induce cell death by disrupting transcription processes, making it a promising candidate for targeted cancer therapies through antibody-drug conjugates (ADCs).

Recent advancements in synthetic methods have made it possible to produce α-amanitin and its derivatives at scale, enabling the development of new ADCs that can effectively deliver this toxin to tumor sites, potentially eliminating malignant cells with very small doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total Synthesis of α- and β-Amanitin. Lutz, C., Simon, W., Werner-Simon, S., et al.[2021]

Monoclonal antibodies, such as daratumumab and elotuzumab, have significantly improved treatment outcomes for multiple myeloma (MM), particularly in patients who are double-refractory, and are becoming essential in the initial treatment of newly diagnosed MM.

The recent approval of belantamab mafodotin, which targets B-cell maturation antigen (BCMA), marks a significant advancement in antibody therapies for advanced MM, demonstrating promising efficacy and manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current antibody-based therapies for the treatment of multiple myeloma. Varga, C., Waldschmidt, JM., Gandolfi, S., et al.[2021]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3381/532944/The-Anti-BCMA-Antibody-Drug-Conjugate-Hdp-101-with

The Anti-BCMA Antibody-Drug Conjugate Hdp-101 with a ... The anti-BCMA antibody-drug conjugate Hdp-101 with a novel amanitin payload shows promising initial first in human results in relapsed multiple myeloma.

2. myeloma.org myeloma.org/sparkcures/trial/1177/NCT04879043/resources

HDP-101 The Anti-BCMA Antibody-Drug Conjugate Hdp-101 with a Novel Amanitin Payload Shows Promising Initial First in Human Results in Relapsed Multiple Myeloma.

3. cancernetwork.com cancernetwork.com/view/hdp-101-receives-fda-fast-track-designation-in-multiple-myeloma

HDP-101 Receives FDA Fast Track Designation in ... “The novel BCMA-targeting ADC HDP-101 shows promising results in heavily pretreated [patients with relapsed/refractory multiple myeloma]. These ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10802748/

Novel Anti-B-cell Maturation Antigen Alpha-Amanitin ... HDP-101 showed potent anti-myeloma activity against all tested cell lines, and exerted enhanced efficacy against POLR2A KD and dual TP53 KO/POLR2A KD cells.

5. library.ehaweb.org library.ehaweb.org/eha/2025/eha2025-congress/4160156/shambavi.richard.the.anti-bcma.antibody-drug.conjugate.hdp-101.with.a.novel.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2882%2Aot_id%3D31552%2Amarker%3D5844%2Afeatured%3D19595

THE ANTI-BCMA ANTIBODY-DRUG CONJUGATE HDP-101 ... THE ANTI-BCMA ANTIBODY-DRUG CONJUGATE HDP-101 WITH A NOVEL AMANITIN PAYLOAD SHOWS PROMISING DATA IN RELAPSED/ REFRACTORY MULTIPLE MYELOMA IN ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04879043

Study to Assess Safety of HDP-101 in Patients With ... This study will assess the safety, tolerability, pharmacokinetics (PK) and the therapeutic potential of HDP-101 in patients with plasma cell disorders ...

7. heidelberg-pharma.com heidelberg-pharma.com/en/press-investors/announcements/press-releases-and-ad-hoc-announcements/pr-heidelberg-pharma-announces-new-clinical-data-on-lead-atac-candidate-hdp-101-to-be-presented-at-international-myeloma-society-annual-meeting-2025

Heidelberg Pharma Announces New Clinical Data on Lead ... HDP-101 is an Anti-BCMA antibody-Amanitin drug conjugate for the treatment of relapsed or refractory multiple myeloma, a bone marrow cancer with ...