PHST001: PHST001 is an anti-CD24 macrophage checkpoint inhibitor, administered as IV infusions every 3-weeks (Q3W) dosing intervals.
Chemotherapy 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.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Key Inclusion Criteria:
* Histologically or cytologically confirmed advanced solid tumor which has relapsed from or been refractory to all locally available standard therapies.
* Adequate organ function per laboratory testing
* Pregnancy prevention requirements
* Measurable disease per RECIST v1.1 (or RANO) as assessed by the local site Investigator/radiology
* Performance status of 0 or 1 on Eastern Cooperative Oncology Group (ECOG) scale
Key Exclusion Criteria:
* Diagnosis of immunodeficiency
* History of a previous additional malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years. Participants with basal cell carcinoma of the skin, Stage I melanoma, melanoma in situ, squamous cell carcinoma of the skin, early-stage prostate cancer, or carcinoma in situ, excluding carcinoma in situ of the bladder, who have undergone potentially curative therapy are not excluded and can be enrolled regardless of disease-free period following completion of potentially curative therapy. Participants with early-stage breast cancer who have undergone curative intent treatment and with no disease recurrence for 2 years after treatment are not excluded.
* Active known CNS metastases and/or carcinomatous meningitis. Participants with previously treated CNS metastases may participate provided they are radiologically stable (i.e., without evidence of progression for at least 2 weeks by repeat imaging \[note that the repeat imaging should be performed during study screening\]), clinically stable, and without requirement of steroid treatment for at least 14 days prior to the first dose of study treatment.
* Received prior systemic anticancer therapy including investigational agents within 21 days or, if shorter, within 5 half-lives prior to the first dose of study treatment. Participants must have recovered from all AEs due to previous therapies to Grade ≤1 or baseline. Participants with Grade ≤2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible.
* Prior autologous or allogeneic hematopoietic stem cell transplant or solid organ transplant.
* Received previous treatment with another agent targeting CD24.
Primary outcome measure(s)
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) — From first dose of PHST001 through 21 days after the first dose of PHST001 Based on toxicities observed
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) — From signed consent up to 90 days after the last dose of PHST001 Based on toxicities observed
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) — From first dose up to 90 days after the last dose of PHST001 Based on toxicities observed
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) — From first dose up to 90 days after the last dose of PHST001 Based on toxicities observed
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) — From first dose up to 90 days after the last dose of PHST001 Based on toxicities observed
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) — From first dose up to 90 days after the last dose of PHST001 Based on toxicities observed
Overall Response Rate (ORR) based on RECIST v1.1 to assess the preliminary antitumor activity of PHST001 in combination with chemotherapy (Phase 1b) — From screening and during treatment up to 2 years 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.
Duration of Response (DOR) based on RECIST v1.1 to assess the preliminary antitumor activity of PHST001 in combination with chemotherapy (Phase 1b) — From screening and during treatment up to 2 years Defined as time from date of first objective response (either CR or PR) to first documentation of radiographic disease progression.
Best Overall Response (BOR) based on RECIST v1.1 to assess the preliminary antitumor activity of PHST001 in combination with chemotherapy (Phase 1b) — From screening and during treatment up to 2 years 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.
Progression-Free Survival (PFS) based on RECIST v1.1 to assess the preliminary antitumor activity of PHST001 in combination with chemotherapy (Phase 1b) — From screening and during treatment up to 2 years Defined as the time from first dose of PHST001 to first documentation of radiographic disease progression or death, whichever occurs first.
Overall Survival (OS) based on RECIST v1.1 to assess the preliminary antitumor activity of PHST001 in combination with chemotherapy (Phase 1b) — From screening and during treatment up to 2 years Defined as the time from first dose of PHST001 to the date of death.
Trial sites (20)
Facility
City
Region
Status
Precision NextGen Oncology & Research Center
Beverly Hills
California
Recruiting
USC Norris Comprehensive Cancer Center
Los Angeles
California
Recruiting
Stanford University School of Medicine
Palo Alto
California
Recruiting
Sarah Cannon Research Institute (SCRI) Oncology Partners - Denver Health One
Denver
Colorado
Recruiting
Yale Cancer Center
New Haven
Connecticut
Recruiting
University of Chicago Medical Center
Chicago
Illinois
Recruiting
Dana Farber Cancer Institute
Boston
Massachusetts
Recruiting
University of Michigan Rogel Cancer Center
Ann Arbor
Michigan
Recruiting
START Center for Cancer Research - Midwest
Grand Rapids
Michigan
Recruiting
START Center for Cancer Research - Long Island New York
Lake Success
New York
Recruiting
Mount Sinai
New York
New York
Recruiting
Duke Cancer Institute
Durham
North Carolina
Recruiting
Sarah Cannon Research Institute (SCRI) Oncology Partners
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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