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 part - To estimate the RP2D or MTD for:
● Single agent LAG525
● Combination of LAG525 and PDR001.
Phase II part - To estimate the overall response rate per RECIST V1.1:
● Single agent LAG525
● Combination of LAG525 and PDR001 |
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E.2.2 | Secondary objectives of the trial |
Key Secondary Objectives:
1) To characterize the safety and tolerability of single agent LAG525 given alone and in combination with PDR001
2) To characterize the pharmacokinetic profile of single agent LAG525 given alone and in combination with PDR001
3) To assess emergence of anti-LAG525, and anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of single agent LAG525 given alone or in combination with PDR001
4) To evaluate the preliminary antitumor activity of single agent LAG525 given alone or in combination of PDR001
Other Secondary Objectives are defined in the protocol. |
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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 procedures
2. Age ≥ 18 years
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 had disease progression following their last prior therapy.
5. ECOG Performance Status ≤ 2.
6. 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 baseline, and during therapy on this study. |
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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 within three years prior to screening.
3. Active infection requiring systemic antibiotic therapy.
4. Known history of HIV infection.
5. Active hepatitis B virus (HBV) or hepatitis C virus (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 is indicated as washout period.
7. Phase II only: Prior PD1- or PD-L1-directed therapy with the exception of patients with renal cell cancer will have been previously treated with anti-PD-1 or anti-PD-L1 inhibitors.
8. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
9. 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 part:
- The incidence of dose limiting toxicities ( DLTs) with single agent LAG525 & for the combination treatment of LAG525 and PDR001
Phase II part: Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. of single agent LAG525 & the combination of LAG525 and PDR001.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase I:
- the incidence of DLTs continously: during the first cycle of treatment with single agent LAG525; for the combination treatment of LAG525 and PDR001, the DLT window will be 2 cycles of the treatment.
Phase II:
- Every 2 Cycles ± 1 week from Cycle 3 Day 1 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. a) Safety incidence and severity if adverse events (AEs) and serious adverse events (SAEs) including changes in laboratory parameters, vital signs and ECGs; b) Tolerability: Dose interruptions, reductions and dose intensity.
2. Serum PK parameters (e.g. AUC, Cmax, Tmax, t1/2 half-life))
3. Presence and/ or concentration of anti-LAG525 and anti-PDR001 antibodies
4. Phase I Part: ORR, progression free survival (PFS), duration of response (DOR) and disease control rate (DCR); Phase II Part: ORR per immune related Response Criteria (irRC), PFS, DOR, DCR per RECIST V1.1 and per irRC
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Assessed continuously
2. Every Cycle until Cycle 6
3. Every Cycle until Cycle 6
4. Every 2 Cycles ± 1 week from Cycle 3 Day 1 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 | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 |
Australia |
Belgium |
Canada |
France |
Germany |
Hong Kong |
Italy |
Japan |
Korea, Republic of |
Singapore |
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 | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |
E.8.9.2 | In all countries concerned by the trial days | 0 |