Solid tumors MedDRA version: 20.0 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864
Conditions
Interventions
Product Code: PDR001 100mg
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Spartalizumab
Current Sponsor code: PDR001
Other descriptive name: PDR001
Concentration unit: mg m
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 progressed following their last prior therapy, and fit into one of the following groups: • Group 1a and 1b: NSCLC • Patients with NSCLC must have had disease recurrence or progression during or after no more than one prior systemic chemotherapy regimen (platinum doublet-based) for advanced or metastatic disease. Prior maintenance therapy is allowed (e.g. pemetrexed, erlotinib, bevacizumab). • Only patients with EGFR mutation-negative tumor are eligible (defined as negative for exon 19 deletions and for the L858R mutation in EGFR at a minimum; however, if more extensive EGFR mutation testing has been performed, the tumor must not harbor any known activating EGFR mutations in Exons 18-21 in order to be considered EGFR mutationnegative). All patients must be tested for EGFR mutational status and, for ALK translocation status if no mutation is detected in EGFR. Patients with ALK translocation-positive NSCLC must have had disease progression following treatment with a corresponding inhibitor and no more than one systemic chemotherapy regimen (platinum doubletbased), in any sequence. • Group 2: Melanoma • All patients must have been tested for BRAF mutations. Patients with BRAF V600 mutation positive melanoma must have clinical or radiological evidence of disease progression during or after • Treatment with a BRAF inhibitor (alone or in combination with other agents) • Group 3: Triple negative breast cancer • Group 4: Anaplastic thyroid cancer • Patients are not required to have received or progressed on a prior therapy. • Patients in this indication must not be at short term risk for life threatening complications (such as airway compromise or bleeding from locoregional or metastatic disease). • Chemoradiation and/or surgery should be considered prior to study entry for those patients with locally advanced disease if those therapies are considered to be in the best interest of the patient. 5. ECOG Performance Status = 1. 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 or at molecular pre-screening if applicable, and during therapy on this study. For patients in the phase II part of the study, exceptions may be granted after documented discussion with Novartis. After a sufficient number of paired biopsies are collected, the decision may be taken to stop the collection of biopsies. 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 182 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 106
Exclusion criteria
Exclusion criteria: 1. History of severe hypersensitivity reactions to other mAbs 2. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 3. History of drug-induced pneumonitis or current pneumonitis. 4. Active infection requiring systemic antibiotic therapy. 5. HIV infection. 6. Active HBV or HCV infection. 7. Patients with ocular melanoma. 8. 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. For patients receiving anticancer immunotherapies such as CTLA-4 antagonists, 6 weeks is indicated as the washout period. 9. Prior PD-1- or PD-L1-directed therapy. 10. Patients requiring chronic 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. 11. Patients receiving systemic treatment with any immunosuppressive medication (other than steroids as described above). 12. Use of any live vaccines within 4 weeks of initiation of study treatment. 13. 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 at cycle 3 - 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 at cycle 3 - the incidence of DLTs: in first cycle of treatment Phase II: - Every 8 weeks ± 1 week from 8 weeks post Cycle 1 Day 1 up to 40 weeks, then every 12 weeks ± 1 week 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 Presence and/or concentration of anti-PDR001 antibodies. 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. Physical examination, vital signs etc: 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. Continous assessment of AEs at every visit. ECG will be assessed at screening and as clinically indicated. 2. Cycle 1 and Cycle 3. 3. Every 8 weeks ± 1 week from 8 weeks post Cycle 1 Day 1 up to 40 weeks, then every 12 weeks ± 1 week until progression of disease per irRC or patient withdrawal. | — |
Countries
Canada, France, Germany, Hungary, Italy, Lebanon, Netherlands, Norway, Poland, Spain, Taiwan, Thailand, Turkey, United States
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed