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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Heidelberg Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Oct 2021 → ongoing

Decision date (initial)

2024-08-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515273-10-00

EudraCT number

2020-003414-12

ClinicalTrials.gov

NCT04879043

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Dose response, Pharmacodynamic, Efficacy

Phase 1:
Determine the maximum tolerable dose (MTD) for each treatment arm and/or select a recommended Phase 2 dose for HDP-101 as monotherapy in patients with relapsed or refractory multiple myeloma (r/r MM).

Phase 2a:
Assess efficacy of HDP-101

Conditions and MedDRA coding

Relapsed or refractory Multiple Myeloma (r/r MM)

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

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 yrs at the time of informed consent.
3. Life expectancy >12 weeks, as determined by the Investigator.
4. ECOG Performance Status (PS) of 0 to 2 (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. a) Phase 1 part only: patients with non-secretory or oligo-secretory myeloma (NSMM) not meeting the measurability criteria described in 8.b) are eligible (all other eligibility criteria must apply). b) Phase 2a part only - 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 CrCl (using 24-hour urine), if a measured CrCl is not available, the calculated creatinine clearance using the Cockcroft-GaultFormula 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 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 >40 MIU/mL and estradiol <40 pg/mL [<147 pmol/L] is confirmatory). Women on hormone replacement therapy 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 confirmation of their postmenopausal status, they can resume use of HRT during the study without use of a contraceptive method. •Women of childbearing potential must have a negative urine pregnancy test 7 days before the first administration of the study treatment and on Day 1 before first dose of study treatment and commit to either abstain continuously from heterosexual intercourse or to use 2 methods of reliable birth control simultaneously, during the study and for 4 months following the last dose of the study treatment. This includes 1 highly effective form of contraception (tubal ligation, intrauterine device, hormonal [birth control pills, injections, hormonal patches, vaginal rings, or implants] or partner's vasectomy) and 1 additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap).
12. Male patients must have had a prior vasectomy or commit to use an effective contraception (complete abstinence from sexual intercourse, latex or synthetic condom and during sexual intercourse with a female a double-barrier method including a condom and occlusive cap [diaphragm or cervical/vault caps] plus spermicidal agent [foam/gel/film/cream/suppository]) from the time of first study treatment infusion until 3 months following the last study treatment infusion to allow for clearance of any altered sperm.

Exclusion criteria 25

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 prior BCMA directed treatment providing they fulfilled all other I/E 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 classified as Class ≥ III based on the NYHA Classification or Grade 3/4 unstable angina pectoris within 6 months of enrollment, presence of unstable atrial fibrillation, electrocardiogram (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. Malignancies which are adequately treated and requiring hormonal therapies only to prevent the recurrence of the malignancy other than multiple myeloma may be permitted after discussion with and agreement of the Sponsor's Medical Monitor (eg, breast cancer treated with hormonal therapies).
16. For sites in Germany: HIV infection at the time of the screening. For all other sites: Known human immunodeficiency virus infection.
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 positive for hepatitis B surface antigen or Hepatitis B core antigen.
19. Patients positive for hepatitis C virus (HCV) infection are excluded regardless of viral load. If the hepatitis C antibody test is positive, a confirmatory PCR or recombinant immunoblot assay (RIBA) test should be performed. If the RIBA test is negative, patient is eligible for study.
20. Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones), liver metastases, or other stable chronic liver disease per the Investigator's assessment.
21. Pregnancy or breast feeding.
22. Refusal to use effective methods of contraception.
23. Legal incapacity/limited legal capacity for providing informed consent.
24. Any serious and/or unstable preexisting medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with patient's safety, obtaining informed consent, or compliance to the study procedures.
25. Pneumonia or symptomatic pneumonitis (symptoms include but not limited to shortness of breath, wheezing, dyspnea, decrease oxygen saturation).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Phase 1: Number of patients who experience a dose-limiting toxicity (DLT) during the first cycle of treatment. Phase 2a: Objective response rate (ORR).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Heidelberg Pharma AG

Sponsor organisation

Heidelberg Pharma AG

Address

Gregor-Mendel-Strasse 22

City

Ladenburg

Postcode

68526

Country

Germany

Scientific contact point

Organisation

Heidelberg Pharma AG

Contact name

Clinical Development

Public contact point

Organisation

Heidelberg Pharma AG

Contact name

Clinical Development

Third parties 13

Locations

5 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 40 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications