E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
- Prostate cancer - Non-small cell lung cancer |
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E.1.1.1 | Medical condition in easily understood language |
- Prostate cancer - Non-small cell lung cancer |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | Prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
-To characterize the safety and tolerability of isatuximab in combination with REGN2810 in patients with metastatic, castration-resistant prostate cancer (mCRPC) who are naïve to anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PDL-1)-containing therapy, or non-small cell lung cancer (NSCLC) who progressed on anti-PD-1/PDL-1-containing therapy, and to confirm the recommended Phase 2 dose (RP2D). - To assess the response rate of isatuximab in combination with REGN2810 in patients with either mCRPC who are anti-PD-1/PDL-1 therapy naive, or NSCLC who progressed on anti-PD-1/PDL-1 therapy, or of isatuximab as single agent in patients with mCRPC |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the safety of the combination of isatuximab with REGN2810 or isatuximab monotherapy. -To evaluate the immunogenicity of isatuximab and REGN2810. -To characterize the pharmacokinetic (PK) profile of isatuximab single agent or in combination with REGN2810, and to characterize the PK of REGN2810 in combination with isatuximab. -To assess overall efficacy of isatuximab in combination with REGN2810 or as a single agent. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients must have a known diagnosis of either metastatic castration-resistant prostate cancer (mCRPC) or non-small cell lung cancer (NSCLC) with evidence of measurable disease. - Failure of, inability to, or refusal to receive standard of care. - ≥18 years of age. |
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E.4 | Principal exclusion criteria |
- Prior exposure to isatuximab or participation in clinical studies with isatuximab. - For patients with mCRPC, prior exposure to any agent (approved or investigational) that blocks the PD-1/PD-L1 pathway. - Evidence of other immune related disease /conditions. - History of non-infectious pneumonitis requiring steroids or current pneumonitis; history of the thoracic radiation. - Has received a live-virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted. - Prior solid organ or hematologic transplant. - Eastern Cooperative Oncology Group performance status (PS) ≥2. - Poor bone marrow reserve. - Poor organ function. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Dose Limiting Toxicities (DLTs): DLTs are following adverse events (AEs) in Cycle 1 unless due to disease progression or an obviously unrelated cause: Grade (G) 4 neutropenia >7 days; G 3 to 4 neutropenia with fever or documented infection; G 3 to 4 thrombocytopenia with bleeding requiring intervention; G 4 nonhematological AE; G ≥2 uveitis; G 3 non-hematological AE >3 days despite supportive care (with defined exceptions); Delay in initiation of the 2nd cycle >14 days for related laboratory abnormalities/AEs. 2) AEs: Number of patients with AEs based on standard and systematic assessment including changes in laboratory tests and vital signs, according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 Grade scaling 3) Response Rate: In non-small cell lung cancer (NSCLC): assessed and objective responses by RECIST 1.1; In metastatic castration-resistant prostate cancer (mCRPC): response will be defined per Prostate Cancer Working Group 3 (PCWG3) criteria |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) Up to 3 weeks after first study treatment administration 2) Up to 30 days after last study treatment administration (Up to approximately 25 months after first study treatment administration) 3) Up to 12 months from last patient in |
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E.5.2 | Secondary end point(s) |
1) Immunogenicity: isatuximab - Levels of anti-drug antibody against isatuximab 2) Pharmacokinetic (PK) parameters: area under the curve (AUC) : AUC is area under the drug concentration versus time curve 3) Tumor burden change: The best percent-change from baseline in a sum of the diameters for all target lesions 4) Duration of response: Defined as the time from the date of the first response that is subsequently confirmed to the date of first confirmed disease progression or death, whichever occurs first. 5) Progress-free survival: Defined as time from the first study treatment administration to the date of first documentation of progressive disease that is subsequently confirmed or the date of death from any cause 6) Assessment of PK parameter: Cmax - Cmax is maximum drug concentration observed 7) Immunogenicity: REGN2810 - Levels of anti-drug antibody against REGN2810 8) Disease control rate: Defined as the proportion of patients with confirmed complete response or partial response or stable disease, as assessed by Investigator relative to the total number of patients in the analysis population |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) and 7) Up to 90 days following the last administration of study treatment or until the sample is negative (Up to approximately 27 months after first study treatment administration) 2) and 6) Up to 3 weeks after first study treatment administration 3), 4), 5) and 8) Up to 12 months from last patient in |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
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 | Yes |
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 | Yes |
E.8.1.6 | Cross over | Yes |
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 | 6 |
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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | No |
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 |
Italy |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 | 9 |