To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-0903 administered daily for the first 21 days every 4 weeks, over a range of doses in patients with advanced solid tumors.
To establish the pharmacokinetics of orally administered TP-0903
To observe patients for any evidence of antitumor activity of TP-0903 by objective radiographic assessment
To study the pharmacodynamics of TP-0903 therapy by:
assessing biomarkers in tumor tissue
assessing biomarkers in peripheral blood mononuclear cells (PBMCs) and serum
To establish the Recommended Phase 2 Dose (RP2D) for future studies with TP-0903
Phase I: To characterize the safety and tolerability of BLZ945 as a single agent and in combination with PDR001 and to identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D). Phase II: To assess the anti-tumor activity of BLZ945 in combination with
PDR001 (and as single agent if appropriate) in patients with advanced solid tumors.
Phase I: To characterize the pharmacodynamics effect of BLZ945 as a single agent and in combination with PDR001. To characterize PK of BLZ945 as a single agent and in combination with PDR001. To assess the preliminary anti-tumor activity of BLZ945 as single agent and in
combination with PDR001. Phase I and II: To assess emergence of anti-PDR001 antibodies when
BLZ945 is administered in combination with PDR001.
Primary Outcome Measures:
The percentage of patients who are alive without disease progression
Assess the percentage of patients without disease progression based on local investigator assessment per RECIST in cohort A and cohort B
To evaluate the efficacy of idasanutlin monotherapy in patients without prior ruxolitinib exposure with hydroxyurea (HU)-resistant/intolerant PV:
for patients with splenomegaly at baseline using composite response criteria (hematocrit [Hct] control without phlebotomy and 35% decrease in spleen size by imaging) at Week 32
for patients without splenomegaly at baseline by Hct control without phlebotomy only at Week 32
Primary Objective: To compare DFS as assessed by the investigator for participants treated with pembrolizumab versus those receiving placebo
Hypothesis: Pembrolizumab is superior to placebo with respect to DFS.
Secondary Objective: To compare OS for participants treated with pembrolizumab versus those receiving placebo
Hypothesis: Pembrolizumab is superior to placebo with respect to OS