E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed/Refractory Multiple Myeloma (RRMM) |
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E.1.1.1 | Medical condition in easily understood language |
Recurrent Multiple Myeloma that does not respond to treatment |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Objectives:
• Assess safety and tolerability at increasing dose levels of HPN217 in successive cohorts of patients with RRMM
• Estimate the maximum tolerated dose (MTD) or select the recommended Phase 2 dose (RP2D)
• Characterize single dose and multiple dose pharmacokinetics (PK) of HPN217 following intravenous (IV) administration |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
• Evaluate preliminary efficacy of HPN217
• Evaluate immunogenicity of HPN217
Exploratory Objective:
• Characterize the impact of HPN217 on soluble serum cytokines, including but not limited to interferon gamma (IFNγ), interleukin (IL)-6, tumor necrosis factor alpha (TNFα), and peripheral and bone marrow mononuclear cells |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Major Inclusion Criteria
1.Received at least 3 prior therapies (including proteasome inhibitor, immune modulatory drug, and an anti-CD38 antibody; patients should not be a candidate for or be intolerant of all established therapies known to provide clinical benefit in multiple myeloma).
2. Measurable disease defined as at least one of the following:
a.S erum M-protein ≥0.5 g/dL
b. Urine M-protein ≥200 mg/24 hours
c. Serum free light chain (FLC) assay: Involved FLC level ≥10 mg/dL (≥100 mg/L)
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
4. Adequate hematologic status, including:
a. Absolute neutrophil count (ANC) ≥1000 cells/μL
b. Platelet count ≥50,000/μL (without transfusions)
c. Hemoglobin ≥8 g/dL
5. Adequate renal function, including:
a. Calculated creatinine clearance ≥30 mL/min using the formula of Cockcroft and Gault
6. Adequate hepatic function, including
a. Total bilirubin ≤1.5 × upper limit of normal (ULN), regardless of direct bilirubin
b. AST and ALT ≤3.0 × ULN (≤5.0× ULN if due to myeloma involvement)
c. Alkaline phosphatase ≤3× ULN (≤5.0× ULN if due to myeloma involvement)
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E.4 | Principal exclusion criteria |
Major Exclusion Criteria
1.Prior exposure to BCMA-targeting agents (Part 2 only)
2. Concurrent treatment with anti-tumor necrosis factor alpha therapies, systemic corticosteroids (prednisone dose >10 mg per day or equivalent), or other immune suppressive drugs within the 2 weeks prior to Screening
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoints:
• Frequency and severity of treatment-emergent AEs (TEAEs) graded according to NCI CTCAE version 5.0.
• Change from baseline in clinical laboratory parameters, vital signs, and ECGs.
• Number and severity of DLTs following treatment with HPN217.
• PK parameters of HPN217:
o Single dose - maximum concentration (Cmax), time to maximum concentration (Tmax), area under the single dose concentration-time curve over dosing interval τ (AUCsd, τ), area under the concentration-time curve extrapolated to infinity (AUCinf), terminal elimination half-life (t1/2), and clearance (CL) as data permit
o Multiple dose (assuming steady state is achieved) - maximum concentration (Css,max), time to maximum concentration (Tss,max), area under the steady state concentration-time curve over dosing interval τ (AUCss, τ), t1/2, minimum concentration (Css,min), CL, volume of distribution (Vss), and accumulation ratio (AUCss,τ/AUCsd, τ) as data permit |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoints of evaluation are outlined in Appendix 1 in the protocol
Response evaluation is outlined in Appendix 3 in the protocol |
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E.5.2 | Secondary end point(s) |
Secondary Endpoints:
• Overall response rate (ORR) based on IMWG response criteria
• Progression-free survival (PFS) and overall survival (OS)
• Duration of response (DOR)
• Incidence and titers of ADAs against HPN217 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints of evaluation are outlined in Appendix 1 in the protocol
Response evaluation is outlined in Appendix 3 in the protocol |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Germany |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |