A Phase 1/2a, First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of HDP-101 in Patients with Plasma Cell Disorders Including Multiple Myeloma

Phase 1

• Conditions: Relapsed or refractory Multiple Myeloma (r/r MM); MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-003414-12-HU
• Lead Sponsor: Heidelberg Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-09-13
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

Patients are eligible to be included in the study only if all of the following criteria apply:
1. Patients who have signed an informed consent and are willing to comply with the requirements and restrictions listed in the study protocol.

2. Male or female aged =18 years at the time of informed consent.

3. Life expectancy >12 weeks, as determined by the Investigator.

4. Eastern Cooperative Oncology Group Performance Status (PS) of 0 to 1 (tumor related performance).

5. A confirmed diagnosis of active MM according to the diagnostic criteria established by the International Myeloma Working Group (IMWG).

6. Must have undergone SCT or is considered transplant ineligible.

7. Must have undergone prior treatments with antimyeloma therapy which must have included an immunomodulatory drug, proteasome inhibitor, and antiCD38 treatment, alone or in combination. Patients who are intolerant to these therapies or have contraindications are eligible if other eligibility criteria are fulfilled. Patient must have failed last line of treatment (refractory to or relapsed after last line of treatment) or had to permanently discontinue the last line of therapy due to toxicity (toxicity and reason for permanent discontinuation has to be documented in the electronic case report form [eCRF]). In addition, the patient should either refractory or intolerant to any established standard of care therapy providing a meaningful clinical benefit for the patient assessed by the Investigator.

8. Measurable disease defined as:
•Serum M-protein =0.5 g/dL, or
•Urine M-protein =200 mg/24 hours, or
•Serum-free light chains (FLC) assay: involved FLC level =10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal (<0.26 or >1.65).

9. Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolved to Grade 0 or 1 as per the NCI-CTCAE version 5.0, except for alopecia and Grade 2 neuropathy.

10. Adequate organ system function as defined:
•Absolute neutrophil counta: =1.0 × 10^9/L
•Platelet count: =75 × 10^9/L and absent platelet transfusion for =7 days
•Hemoglobin: >8.0 g/dL and absent RBC transfusion for =7 days
•Activated partial thromboplastin time/partial thromboplastin time: =1.5 × ULN
•Measured creatinine clearance (using 24-hour urine), if a measured Cr-Cl is not available, the calculated creatinine clearance using the Cockcroft-Gault-Formula can be used: =60 mL/min
•Albuminuria: =500 mg/24 hours
•Total serum bilirubin: =1.5 × ULN (isolated bilirubin >1.5 and =3.0 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
•Aspartate and alanine transaminases: =1.5 × ULN

11. A female patient is eligible to participate if she is of
•Nonchildbearing potential (ie, physiologically incapable of becoming pregnant) defined as premenopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle-stimulating hormone [FSH] >40 MIU/mL and estradiol <40 pg/mL [<147 pmol/L] is confirmatory). Women on hormone replacement therapy (HRT) and whose menopausal status is in doubt are treated like women of childbearing potential unless they discontinue their HRT to allow confirmation of postmenopausal status prior to study enrollment. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmati

Exclusion Criteria

Patients are excluded from the study if any of the following criteria apply:

1. For patient entering the Phase 2a part only: Prior treatment with any approved or experimental BCMA-targeting modalities are not allowed including but not limited to chimeric antigen receptor T or NK cell treatment, mono or bispecific antibodies and other BCMA-ADCs. (Note that patients in the Phase 1 part could have had any type of prior BCMA directed treatment providing they fulfilled all other inclusion and exclusion criteria).

2. History of allergic reactions to any component of the study treatment.

3. Known central nervous system involvement.
4. Plasma cell leukemia (total plasma cell count of at least 2 × 10^9/L) at Screening.

5. History of congestive heart failure New York Heart Association Grade 3/4 unstable angina pectoris, unstable atrial fibrillation, ECG with QTc =480 ms, cardiac arrhythmia, or uncontrolled hypertension.

6. Treatment with systemic anticancer therapy within 4 weeks or 5 t½s of the agent if t½ is known (whichever is shorter) before first dose of the study treatment. Anticancer therapies include cytotoxic chemotherapy, targeted inhibitors, and immunotherapies, but do not include radiotherapy or corticosteroids.

7. Higher dose of systemic corticosteroids, defined as oral dexamethasone >40 mg/day (for patients aged >75 years reduced to >20 mg/day) or equivalent, within 3 days prior to the first study treatment infusion.

8. Currently participating in a study and receiving study therapy or participated in a study of an investigational agent and received study therapy or used an investigational device within 2 weeks of the first dose of study treatment.

9. Autologous or allogenic SCT within 12 weeks before the first infusion or is planning for autologous SCT.

10. Symptomatic graft versus host disease post allogenic hemopoietic cell transplant within 12 months prior to the first study treatment infusion.

11. Significant surgical intervention within 21 days prior to the first study treatment infusion or ongoing post-operative complications.

12.Patients who have a history of being nonresponsive to platelet and/or RBC transfusions and expected lack of adequate support with blood products on demand.

13. Radiotherapy within 21 days prior to the first study treatment infusion, or localized palliative radiotherapy within 7 days prior to the first study treatment infusion, therapy with radio immuno-conjugates performed less than 3 months prior to the first dose of study treatment.

14. Herbal remedies interfering or stimulating the metabolic pathways (eg, mistletoe extract) or known to potentially interfere with major organ function (eg, hypericin) within 21 days prior to the first study treatment infusion.

15. History of any other malignancy known to be active, with the exception of completely removed in situ cervical intraepithelial neoplasia, nonmelanoma skin cancer, ductal carcinoma in situ, early stage prostate cancer that has been adequately treated.

16. Human immunodeficiency virus infection at the time of the screening.

17. Patients with active infection requiring systemic anti-infective (eg, antibiotic or antiviral) therapy. Patients who are successfully treated with systemic anti-infective treatment and have no clinical signs of infection for at least 2 days may be enrolled as per the discretion of the Investigator.

18. Patients with positive test results for hepatitis B surface antigen or Hepatitis B core antigen.

19.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified