An Open-label, Phase 1a/1b, Dose Escalation and Dose Expansion Study Investigating the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of PHST001 in Adult Patients With Advanced Relapsed and/or Refractory Solid Tumors
Summary
This is a multi-center, first-in-human (FIH), open-label, Phase 1a/1b dose escalation and dose expansion study to assess the safety, PK, pharmacodynamics, and antitumor activity of PHST001 monotherapy (Phase 1a) or in combination with chemotherapy (Phase 1b) in adult participants with advanced relapsed and/or refractory solid tumors (including but not limited to CNS tumors in Phase 1a only). In Phase 1b cohort expansions, the study will focus on participants with advanced relapsed and/or refractory ovarian cancer, endometrial cancer, and cholangiocarcinoma. The study's primary objective is to evaluate the safety and tolerability of PHST001 and determine the RP2D (Recommended Phase 2 dose) of PHST001 monotherapy and in combination with chemotherapy as well as assess the anti-tumor activity of PHST001 and chemotherapy in Phase 1b.
Arms & interventions
- BiologicalPHST001
PHST001 is an anti-CD24 macrophage checkpoint inhibitor, administered as IV infusions every 3-weeks (Q3W) dosing intervals.
- DrugChemotherapy per Standard of Care
Participants will receive PHST001 at a dose level and schedule based on monotherapy data in Phase 1a. PHST001 will be combined with chemotherapeutic agents used as standard of care.
Outcome measures
Primary
Frequency of Dose-Limiting Toxicities (DLTs) to assess the safety and tolerability of PHST001 as monotherapy (Phase 1a) or in combination with chemotherapy (Phase 1b)
Based on toxicities observed
Time frame: From first dose of PHST001 through 21 days after the first dose of PHST001
Frequency of Serious Adverse Events (SAEs) to assess the safety and tolerability of PHST001 as monotherapy (Phase 1a) or in combination with chemotherapy (Phase 1b)
Based on toxicities observed
Time frame: From signed consent up to 90 days after the last dose of PHST001
Frequency of Treatment Emergent Adverse Events (TEAEs) to assess the safety and tolerability of PHST001 as monotherapy (Phase 1a) or in combination with chemotherapy (Phase 1b)
Based on toxicities observed
Time frame: From first dose up to 90 days after the last dose of PHST001
Frequency of Treatment Related Adverse Events (TRAEs) to assess the safety and tolerability of PHST001 as monotherapy (Phase 1a) or in combination with chemotherapy (Phase 1b)
Based on toxicities observed
Time frame: From first dose up to 90 days after the last dose of PHST001
Frequency of Adverse Events of Special Interest (AESIs) to assess the safety and tolerability of PHST001 as monotherapy (Phase 1a) or in combination with chemotherapy (Phase 1b)
Based on toxicities observed
Time frame: From first dose up to 90 days after the last dose of PHST001
Frequency of AEs Leading to Dose Interruption or Treatment Discontinuation and AEs Leading to Death to assess the safety and tolerability of PHST001 as monotherapy (Phase 1a) or in combination with chemotherapy (Phase 1b)
Based on toxicities observed
Time frame: From first dose up to 90 days after the last dose of PHST001
Overall Response Rate (ORR) based on RECIST v1.1 to assess the preliminary antitumor activity of PHST001 in combination with chemotherapy (Phase 1b)
Defined as the proportion of subjects with confirmed complete response (CR) or partial response (PR); a confirmed response is a response that persists on repeat-imaging ≥ 4 weeks after initial documentation of response.
Time frame: From screening and during treatment up to 2 years
Duration of Response (DOR) based on RECIST v1.1 to assess the preliminary antitumor activity of PHST001 in combination with chemotherapy (Phase 1b)
Defined as time from date of first objective response (either CR or PR) to first documentation of radiographic disease progression.
Time frame: From screening and during treatment up to 2 years
Best Overall Response (BOR) based on RECIST v1.1 to assess the preliminary antitumor activity of PHST001 in combination with chemotherapy (Phase 1b)
Defined as the best response recorded for a participant across all time-point assessments from the start of treatment until disease progression or end of treatment.
Time frame: From screening and during treatment up to 2 years
Progression-Free Survival (PFS) based on RECIST v1.1 to assess the preliminary antitumor activity of PHST001 in combination with chemotherapy (Phase 1b)
Defined as the time from first dose of PHST001 to first documentation of radiographic disease progression or death, whichever occurs first.
Time frame: From screening and during treatment up to 2 years
Overall Survival (OS) based on RECIST v1.1 to assess the preliminary antitumor activity of PHST001 in combination with chemotherapy (Phase 1b)
Defined as the time from first dose of PHST001 to the date of death.
Time frame: From screening and during treatment up to 2 years
Secondary
Overall Response Rate (ORR) based on RECIST v1.1 (or RANO for primary CNS Tumors) to assess the preliminary antitumor activity of PHST001 as monotherapy (Phase 1a)
Time frame: From screening and during treatment up to 2 years
Duration of Response (DOR) based on RECIST v1.1 (or RANO for primary CNS Tumors) to assess the preliminary antitumor activity of PHST001 as monotherapy (Phase 1a)
Time frame: From screening and during treatment up to 2 years
Best Overall Response (BOR) based on RECIST v1.1 (or RANO for primary CNS Tumors) to assess the preliminary antitumor activity of PHST001 as monotherapy (Phase 1a)
Time frame: From screening and during treatment up to 2 years
Progression-Free Survival (PFS) based on RECIST v1.1 (or RANO for primary CNS Tumors) to assess the preliminary antitumor activity of PHST001 as monotherapy (Phase 1a).
Time frame: From screening and during treatment up to 2 years
Overall Survival (OS) based on RECIST v1.1 (or RANO for primary CNS Tumors) to assess the preliminary antitumor activity of PHST001 as monotherapy (Phase 1a).
Time frame: From screening and during treatment up to 2 years
Maximum Observed Concentration (Cmax) to characterize the serum PK of PHST001 as monotherapy (Phase 1a) or in combination with chemotherapy (Phase 1b).
Time frame: From treatment until 90 days after last dose of PHST001
Time to Maximum Concentration (tmax) to characterize the serum PK of PHST001 as monotherapy (Phase 1a) or in combination with chemotherapy (Phase 1b)
Time frame: From treatment until 90 days after last dose of PHST001
Concentration at the End of a Dosing Interval (Ctrough) to characterize the serum PK of PHST001 as monotherapy (Phase 1a) or in combination with chemotherapy (Phase 1b)
Time frame: From treatment until 90 days after last dose of PHST001
Area Under the Concentration-time Curve (AUC) to characterize the serum PK of PHST001 as monotherapy (Phase 1a) or in combination with chemotherapy (Phase 1b)
Time frame: From treatment until 90 days after last dose of PHST001
Volume of Distribution at Steady-state (Vss) to characterize the serum PK of PHST001 as monotherapy (Phase 1a) or in combination with chemotherapy (Phase 1b)
Time frame: From treatment until 90 days after last dose of PHST001
Clearance (CL) to characterize the serum PK of PHST001 as monotherapy (Phase 1a) or in combination with chemotherapy (Phase 1b)
Time frame: From treatment until 90 days after last dose of PHST001
Terminal Elimination Half-life (t½) to characterize the serum PK of PHST001 as monotherapy (Phase 1a) or in combination with chemotherapy (Phase 1b)
Time frame: From treatment until 90 days after last dose of PHST001
Eligibility criteria
Study locations (20)
Precision NextGen Oncology & Research Center
Beverly Hills, California, 90212
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Stanford University School of Medicine
Palo Alto, California, 94304
Sarah Cannon Research Institute (SCRI) Oncology Partners - Denver Health One
Denver, Colorado, 80218
Yale Cancer Center
New Haven, Connecticut, 06520
University of Chicago Medical Center
Chicago, Illinois, 60637
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
START Center for Cancer Research - Midwest
Grand Rapids, Michigan, 49546
START Center for Cancer Research - Long Island New York
Lake Success, New York, 11042
Mount Sinai
New York, New York, 10029
Duke Cancer Institute
Durham, North Carolina, 27710
Sarah Cannon Research Institute (SCRI) Oncology Partners
Nashville, Tennessee, 37203
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37203
START Center for Cancer Research - Texas
Fort Worth, Texas, 76104
MD Anderson Cancer Center
Houston, Texas, 77030
NEXT Oncology - Dallas
Irving, Texas, 75039
South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas, 78229
University of Texas (UT) Health
San Antonio, Texas, 78229
NEXT Oncology - Virginia
Fairfax, Virginia, 22031