E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 10048683 |
E.1.2 | Term | Advanced cancer |
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 |
Phase Ib part:
To characterize the safety and tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
Phase II part:
To estimate the anti-tumor activity of the combination of MCS110 with PDR001
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E.2.2 | Secondary objectives of the trial |
Phase Ib part:
1. To estimate the preliminary anti-tumor activity of the combination of MCS110 with PDR001
Phase II part:
2. To further characterize the safety and tolerability of MCS110 given in combination with PDR001
3. To evaluate the preliminary anti-tumor activity of the combination of MCS110 with PDR001 by additional efficacy measures
Phase Ib and Phase II parts:
4. To characterize the pharmacokinetics of MCS110 and PDR001 in combination
5. To assess immunogenicity of MCS110 and PDR001
6. To describe survival with MCS110 and PDR001 in combination |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥ 18 years.
•Phase Ib part: Patients with advanced melanoma, endometrial carcinoma, pancreatic or triple negative breast cancer, with measurable or non-measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
•Phase II part: Patients with advanced solid tumors with at least one measurable lesion as determined by RECIST version 1.1, who have received standard therapy or are intolerant of standard therapy, who have progressed following their last prior therapy, and fit into one of the following groups:
- Group 1: TNBC who did not receive prior anti-PD-1/PD-L1 treatment
- Group 2 : Pancreatic adenocarcinoma who did not receive prior anti-PD-1/PD-L1 treatment
- Group 3 : Endometrial carcinoma who did not receive prior anti-PD-1/PD-L1 treatment
- Group 4: Melanoma who progressed on prior PD-1- and PD-L1-directed therapies.
• ECOG Performance Status ≤ 2.
• Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution’s guidelines. Patient must be willing to undergo a new tumor biopsy at screening, and during therapy on this study. Exceptions for patients with sites of disease not amenable to biopsy may be considered after discussion with the sponsor.
Other inclusion criteria as per protocol may apply. |
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E.4 | Principal exclusion criteria |
• Presence of symptomatic CNS metastases, or CNS metastases thatrequire local CNS-directed therapy
• History of severe hypersensitivity reactions to other mAbs
• Impaired cardiac function or clinically significant cardiac disease
• Active autoimmune disease or a documented history of autoimmune disease within three years before screening
• Active infection requiring systemic antibiotic therapy
• Known history of HIV infection
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, or requiring antiviral treatment
Other exclusion criteria as per protocol may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1b part:
Frequency, severity and seriousness of AEs, laboratory abnormalities and other safety parameters.
Dose interruptions, reductions, and dose intensity.
Incidence rate of DLTs
Phase II part:
Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) (groups 1, 3 and 4).
Clinical benefit rate (CBR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1), which is defined as confirmed objective response or SD>4 months. (Group 2) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase 1b part:
hroughout study conduct
Incidence rate of DLTs: during the first two cycles of study treatment.
Phase II part:
at protocol-defined timepoints |
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E.5.2 | Secondary end point(s) |
Phase Ib part:
1. ORR, progression free survival (PFS), CBR,duration of response (DOR) and disease control rate (DCR) per RECIST v1.1 and per immune related Response Criteria (irRC)
Phase II part:
2. Frequency, severity and seriousness of AEs, laboratory abnormalities and other safety parameters.
3. ORR per irRC, PFS, DOR, DCR, CBR per RECIST v1.1 and per irRC (Group 1, 3 and 4)
4. ORR per irRC, PFS, DOR, DCR, ORR per RECIST v1.1 and per irRC (Group 2)
Phase Ib and Phase II parts:
4. Serum concentration of MCS110 and PDR001 and PK parameters
5. Presence and/or concentration of anti-PDR001 or anti-MCS110 antibodies
6. Overall survival (OS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at protocol-defined timepoints (PK, PD and preliminary anti-tumor activity endpoint). |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
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 | 8 |
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 |
Belgium |
Finland |
France |
Germany |
Hong Kong |
Italy |
Japan |
Korea, Republic of |
Spain |
Switzerland |
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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The end of the study will be when 80% of the patients have completed the survival follow-up period (minimum 18 months after the first dose of treatment) or discontinued the study for any reason, and all patients have completed treatment and the safety follow-up period (150 days after last PDR001 dose or 90 days for patients who stopped PDR001 and continued with MCS110 alone for more than 60 days), or the study is terminated early, or another clinical study becomes available [...]. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
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 | 7 |