Patients with advanced malignancies : melanoma, NSCLC, TNBC and anaplastic thyroid cancer NSCLC
Conditions
Interventions
Biological: PDR001
anti-PD1 antibody
ICF, medical history, demography, radiology, vital signs, IMP administration
Sponsors
Novartis Pharma Services Inc.
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: •Written informed consent must be obtained prior to any screening procedures •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. •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 mutation-negative). 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 doublet-based), in any sequence. •Group 2: Melanoma: All patients must have been tested for BRAF mutations. Patients with 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 negatice breast cancer. •Group 4: Anaplastic thyroid cancer •Patients are not required to have received or progressed on a prior therapy. •Patients 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. ?ECOG Performance Status = 1. ?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.
Exclusion criteria
Exclusion criteria: •History of severe hypersensitivity reactions to other mAbs •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. •Active infection requiring systemic antibiotic therapy. •HIV infection. •Active HBV or HCV infection. •Patients with ocular melanoma. •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. •Prior PD-1- or PD-L1-directed therapy. •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. •Patients receiving systemic treatment with any immunosuppressive medication (other than steroids as described above). •Use of any vaccines against infectious diseases (e.g. influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment. •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 Inclusion/Exclusion may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: Overall response Rate (ORR);Timepoints: 6 cycles ;Measure: all patients have completed at least 6 cycles of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: •Safety and Tolerability as assessed by incidence and severity of adverse events, dose interruptions, reductions and dose intensity ;Timepoints: Continuously;Measure: Continuously;Name: •Overall Response Rate (ORR);Timepoints: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression ;Measure: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression ;Name: •Progression Free Survival (PFS);Timepoints: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression ;Measure: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression | — |
Countries
Canada, France, Germany, Hungary, Italy, Lebanon, Netherlands, Norway, Poland, Spain, Taiwan, Turkey, United States of America
Contacts
Public ContactJoseph Kattan
Hotel Dieu De France
Outcome results
None listed