The purpose of this "first-in-human" study of PDR001 is to characterize the safety,
tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001
administered i.v. as a single agent to adult patients with solid tumors.
By blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, PDR001 inhibits
the PD-1 immune checkpoint, resulting in activation of an antitumor immune response by
activating effector T-cells and inhibiting regulatory T-cells.
This study has been designed as a phase I/II, multi-center, open-label study starting with a
phase I dose escalation part followed by a phase II part.
PDR001 will be administered every 2 weeks until patient experiences unacceptable toxicity,
progressive disease per immune related Response Criteria (irRC) and/or treatment is
discontinued at the discretion of the investigator or the patient.
- 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 received standard
therapy (with the exception of PD-1- and PD-L1-directed therapies) or are intolerant
of standard therapy, have progressed following their last prior therapy, and fit into
one of the following groups:
- Group 1: NSCLC:
Patients with NSCLC must have had disease recurrence or progression during or after one
prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease.
Prior maintenance therapy is allowed (e.g. pemetrexed, erlotinib, bevacizumab).
Patients must have been tested for mutations affecting EGFR and ALK. Patients with a known
mutation in one gene need not be tested for the other. Patients with ALK or EGFR-positive
NSCLC must have had recurrent or progressive disease after treatment with the
corresponding inhibitor and platinum doublet-based chemotherapy, in any sequence.
- Group 2: Melanoma:
Patients with melanoma must have clinical or radiological evidence of disease progression
during or after:
- For patient with BRAF wild type disease, at least one cycle of systemic treatment for
- For patients with BRAF V600 mutation positive disease, treatment with a BRAF
inhibitor (alone or in combination with other agents) and at least one other systemic
- Group 3: Triple negatice breast cancer.
- ECOG Performance Status 2.
- 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. 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.
- 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
- 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.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Safety and Tolerability as assessed by incidence and severity of adverse events, dose interruptions, reductions and dose intensity
Presence and/or concentration of anti-PDR001
Overall Response Rate (ORR) - Phase l only
Progression Free Survival (PFS) - Phase l/ll
Duration of Response (DOR) - Phase l/ll
Disease Control Rate (DCR) - Phase l/ll
Overall Response Rate (ORR) per immune related Response Criteria - Phase ll only
Composite Serum pharmacokinetics (PK) parameters
Serum concentration vs. time profiles