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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase I: To estimate the RP2D and/or the MTD for PDR001
Phase II: To estimate the anti-tumor activity of PDR001 |
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E.2.2 | Secondary objectives of the trial |
1- To characterize the safety and tolerability of PDR001
2- To characterize the pharmacokinetic profile of PDR001
3- To further investigate the anti-tumor activity of PDR001
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent must be obtained prior to any screening procedures
2. Patient (male or female) ≥ 18 years of age
3. Phase I part: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1 (refer to Appendix 1), who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
4. Phase II part: Patients with advanced/metastatic 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, have progressed following their last prior therapy, and fit into one of the following groups:
• Group 1: NSCLC (no selection for PD-L1)
• Group 2: Melanoma (no selection for PD-L1)
• Group 3: Gastric cancer and esophageal adenocarcinoma (including tumors involving the gastro-esophageal junction) positive for PD-L1 expression.
• Group 4: CRC that is MSI-High (MSI-H), positive for PD-L1 expression
• Group 5: Anal cancer positive for PD-L1 expression
5. ECOG Performance Status ≤ 2.
6. Patients must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy. Patient must be willing to undergo a new tumor biopsy at baseline, and during therapy on this study.
Other protocol-defined inclusion criteria may apply |
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E.4 | Principal exclusion criteria |
1. History of severe hypersensitivity reactions to other mAbs
2. Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy.
3. Active infection requiring systemic antibiotic therapy.
4. Known history of HIV infection.
5. Active HBV or HCV infection.
6. Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas, 4 weeks washout period.
7. Prior PD-1- or PD-L1-directed therapy.
8. Patients receiving treatment with systemic steroid therapy, other than replacement-dose steroids in the setting of adrenal insufficiency. Topical, inhaled, nasal and ophthalmic steroids are not prohibited.
9. Patients receiving systemic treatment with any immunosuppressive medication.
10. Use of any vaccines against infectious diseases (e.g. influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment.
11. Presence of ≥ CTCAE grade 2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer therapy.
Other protocol-defined exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I:
- The exposure (AUC(0-336h)) after first dose of treatment
- The incidence of DLTs
Phase II: Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase I:
- The AUC(0-336h) : after first dose of treatment
- the incidence of DLTs: in first cycle of treatment
Phase II: Every 2 Cycles ± 1 week from Cycle 3 Day 1 up to Cycle 11 Day 1, then every 3 cycles until progression of disease per irRC or patient withdrawal.
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E.5.2 | Secondary end point(s) |
1- Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory parameters, vital signs and electrocardiograms (ECGs)
Tolerability: Dose interruptions, reductions and dose intensity
2- Serum PK parameters (e.g., AUC, Cmax, Tmax, half-life); Serum concentration vs. time profiles
3- Phase I: ORR, progression free survival (PFS), duration of response (DOR) and disease control rate (DCR)
Phase II: ORR per immune related Response Criteria (irRC), PFS, DOR, DCR |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Every week until Cycle 1 Day 15. Every two weeks from Cycle 1 Day 15 until Cycle 3 Day 1. Every cycle from Cycle 3 Day 1 onwards.
2. First half of cycle 1 and first half of cycle 3.
3. Every 2 Cycles ± 1 week from Cycle 3 Day 1 up to Cycle 11 Day 1, then every 3 cycles until progression of disease per irRC or patient withdrawal.
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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 | 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 | 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
| Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Canada |
France |
Germany |
Japan |
Netherlands |
Spain |
Taiwan |
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 per disease group in the phase II part have completed the follow-up for disease progression or discontinued the study for any reason, and all patients have completed treatment and the 30 day safety follow-up period, or if the study is terminated early. |
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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 | 4 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |