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.
Determine the safety and tolerability, including Dose Limiting Toxicities (DLTs), Maximum Tolerated Dose (MTD), and recommended Phase 2 dose (RP2D) of PU-H71 in combination with ruxolitinib in subjects with PMF, post-PV MF, or post-ET MF with residual signs or symptoms of their disease despite at least 6 months treatment with ruxolitinib (Dose
Confirm the safety profile and RP2D of PU-H71 in combination with ruxolitinib in this patient population (Dose Confirmation).
Determine the pharmacokinetics (PK) of PU-H71 in combination with ruxolitinib under the conditions of this study.
To determine whether, in men with post-prostatectomy PSA recurrences, salvage radiation (SRT) with enhanced anti-androgen therapy with apalutamide will improve biochemical progression-free survival (bPFS) compared to SRT alone. A bPFS event is defined as a rise in PSA > 0.2 ng/mL from nadir, confirmed by a second PSA measurement ; clinical or radiographic local, regional, or distant metastases; or death from any cause, whichever occurs first.
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