Relapsed or refractory Multiple Myeloma (r/r MM) MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Heidelberg Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible to be included in the study only if all 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 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). 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 (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, except for alopecia and Grade 2 neuropathy. 10.Adequate organ system function asdefined: •Absolute neutrophil count: =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/24hours •Total serum bilirubin: =1.5 × ULN (isolated bilirubin >1.5 and =3.0 × ULN is acceptable if bilirubin is fractionated and direct bilirubin 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 betw
Exclusion criteria
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 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, 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 oraldexamethasone >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. Pat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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;Secondary Objective: Phase 1 - Assess the safety and tolerability of HDP-101 as monotherapy - Assess the efficacy of HDP-101 monotherapy - To assess the anticancer activity of HDP-101 in terms of time-to-event (TTE) in patients with r/r MM - To evaluate the exposure of HDP-101 and its major metabolites following HDP-101 intravenous(IV) single and repeated dose administration in patients with r/r MM - Evaluate clearance of HDP-101 - To assess immunogenicity of HDP-101 after single and repeated IV dosing Phase 2a: - Assess the safety and tolerability of HDP-101 as monotherapy - To assess the efficacy of HDP-101 monotherapy - To assess the anticancer activity of HDP-101 in TTE in patients with relapsed or refractory multiple myeloma (r/r MM) - To evaluate the exposure of HDP-101 and its major metabolites following "HDP-101" (IV) single and repeated dose administration in patients with r/r MM - Evaluate clearance of HDP-101 - To assess immunogenicity of HDP-101 after single and repeated IV dosing;Primary end point(s): Phase 1: Number of patients who experience a dose-limiting toxicity (DLT) during the first cycle of treatment. Phase 2a: Objective response rate (ORR). ;Timepoint(s) of evaluation of this end point: Phase 1: End of cycle 1. Phase 2a: Beginning of each cycle. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Phase 1: - Efficacy at every cycle. - Safety, immunogenecity and pharmacokinetic at the end of patient treatment. Phase 2a: Time-to-event efficacy the end point will be assessed by the end of follow up.;Secondary end point(s): Phase 1: • Number of patients with treatment emergent adverse events (TEAEs) grouped by system organ class and preferred terms based on Common Terminology Criteria for Adverse Events (CTCAE) classification. • Number of patients with treatment emergent serious adverse events (SAEs) grouped by system organ class and preferred terms based on CTCAE classification. • Number of patients with treatment emergent changes in selected safety laboratory parameters. • Number of patients with treatment emergent, clinically significant changes in vital signs. • Number of patients with clinically significant treatment-emergent, clinically significant changes in electrocardiogram evaluations. • Number of patients with treatment emergent abnormal findings in physical examinations. • Number of patients with dose interruptions and dose reductions. • Objective response rate (ORR). • Best overall response (BOR). • Maximum percentage change of serum or urine M protein or free light chain compared with baseline concentrations. • Clinical benefit rate (CBR) at months 3, 6, 9, and 12. • Number of patients who achieve minimal residual disease (MRD) free status. • Progression-free survival (PFS). • Overall survival (OS). • Overall survival rate. • Duration of response (DOR). • Duration of CBR or better. • Time to objective response (TOR). • Pharmakokinetic parameters as data permit of HDP 101 and its major metabolites in blood samples: maximum concentration (Cmax), minimum concentration (Cmin), time to Cmax (tmax), half life (t½), area under the curve (AUC) through infinity [AUC(0-inf)], AUC through last concentration [AUC(0-last)], AUC through Day 21 [AUC(0-21 d)], area under the curve (AUC) through the dosing interval | — |
Countries
Germany, Hungary, Poland, United States
Contacts
Public ContactClinical Development
Heidelberg Pharma AG
Outcome results
None listed