Solid tumors
Conditions
Interventions
Product Code: PDR001
Pharmaceutical Form: Lyophilisate for solution for infusion
Current Sponsor code: PDR001
Other descriptive name: PDR001
Concentration unit: mg/ml milligram(s)/millilitre
Concentra
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 105 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 56
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: To estimate the RP2D and/or the MTD for PDR001 Phase II: To estimate the anti-tumor activity of PDR001;Secondary Objective: 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 ;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.;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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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;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. | — |
Countries
Canada, France, Germany, Hungary, Italy, Japan, Netherlands, Norway, Spain, Taiwan, United States
Contacts
Public ContactInformation&CommunicationMédicales
Novartis Pharma S.A.S.
Outcome results
None listed