HDP-101 for Multiple Myeloma

Recruiting at14 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

This trial is testing HDP-101, a new treatment for patients with plasma cell disorders like multiple myeloma who haven't responded to other treatments. HDP-101 works by targeting a protein on cancer cells to help the immune system destroy them.

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.

What data supports the effectiveness of the drug HDP-101 for multiple myeloma?

Research shows that HDP-101, which targets a protein on myeloma cells, effectively kills both active and resting cancer cells in lab tests and animal studies. It was well tolerated in monkeys and led to tumor shrinkage, suggesting it could be a promising new treatment for multiple myeloma. ^{1 2 3 4 5}

Is HDP-101 safe for humans?

HDP-101, an antibody-drug conjugate, was well tolerated in animal studies, showing promise for safety in humans. It specifically targets myeloma cells, reducing the risk of affecting healthy cells. ^{1 6 7 8 9}

What makes the drug HDP-101 unique for treating multiple myeloma?

HDP-101 is unique because it combines an antibody that targets a specific protein on myeloma cells with a toxin called amanitin, which can kill both active and resting cancer cells. This approach helps overcome drug resistance and is delivered safely to the cancer cells, minimizing harm to healthy cells. ^{1 2 10 11 12}

Research Team

Eligibility Criteria

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 tested positive for hepatitis C.

My cancer has spread to my brain or spinal cord.

Trial Timeline

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

Treatment Details

Interventions

• HDP-101 (Other)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Antibody-maytansinoid conjugates for the treatment of myeloma. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Current antibody-based therapies for the treatment of multiple myeloma. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

SAR442085, a novel anti-CD38 antibody with enhanced antitumor activity against multiple myeloma. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Amanitins and their development as a payload for antibody-drug conjugates. [2019]

7. United States 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. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Total Synthesis of α- and β-Amanitin. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Management of Ocular Toxicity in Patients Receiving Belantamab Mafodotin. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Humanized anti-HM1.24 antibody mediates myeloma cell cytotoxicity that is enhanced by cytokine stimulation of effector cells. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Generation of monoclonal antibodies to surface proteins of human multiple myeloma employing membrane extracts for murine in vivo immunizations. [2009]

12. United States pubmed.ncbi.nlm.nih.gov

CD26 is a potential therapeutic target by humanized monoclonal antibody for the treatment of multiple myeloma. [2019]