A Study of PHST001 in Advanced Solid Tumors

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

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.

Study Overview

• Status: Recruiting
• Conditions: Ovarian Cancer; Advanced Solid Tumors; Cholangiocarcinoma; Endometrial Cancer; CNS Tumor
• Intervention / Treatment: Biological: PHST001; Drug: Chemotherapy per Standard of Care

• Study Type: Interventional
• Enrollment (Estimated): 272
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Andrew Ferguson/VP Clinical Development, PhD; Phone Number: 434-249-2349; Email: medical@pheast.com

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90212
      • Not yet recruiting
      • Precision NextGen Oncology & Research Center
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC Norris Comprehensive Cancer Center
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University School of Medicine
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Sarah Cannon Research Institute (SCRI) Oncology Partners - Denver Health One
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Rogel Cancer Center
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • START Center for Cancer Research - Midwest
  • New York
    • Lake Success, New York, United States, 11042
      • Recruiting
      • START Center for Cancer Research - Long Island New York
    • New York, New York, United States, 10029
      • Not yet recruiting
      • Mount Sinai
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute (SCRI) Oncology Partners
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • START Center for Cancer Research - Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
    • Irving, Texas, United States, 75039
      • Recruiting
      • Next Oncology - Dallas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • South Texas Accelerated Research Therapeutics (START)
    • San Antonio, Texas, United States, 78229
      • Not yet recruiting
      • University of Texas (UT) Health
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Oncology - Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation (Phase 1a); Nine dose levels will be sequentially tested in PHST001 monotherapy dose escalation: 0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 4.0 mg/kg, 6.0 mg/kg, 9.0 mg/kg, 18.0 mg/kg, and 36.0 mg/kg.	Biological: PHST001; PHST001 is an anti-CD24 macrophage checkpoint inhibitor, administered as IV infusions every 3-weeks (Q3W) dosing intervals.
Experimental: Dose Expansion (Phase 1b); PHST001 will be administered in combination with chemotherapy for three indicated tumor types: ovarian cancer, endometrial cancer, and cholangiocarcinoma. The first portion of Phase 1b will consist of safety run-in groups based on the chemotherapy combination. There will be six groups: 1) combination with paclitaxel, 2) combination with topotecan, 3) combination with doxorubicin, 4) combination with 5-fluorouracil, folinic acid, and irinotecan [FOLFIRI], 5) combination with 5-fluorouracil, folinic acid, and oxaliplatin [FOLFOX], and 6) combination with gemcitabine. The second portion of Phase 1b will begin following clearance of a safety run-in group, and subsequent participants will enroll into tumor-specific expansion cohorts at a fixed dose of PHST001 in combination with chemotherapy.	Biological: PHST001; PHST001 is an anti-CD24 macrophage checkpoint inhibitor, administered as IV infusions every 3-weeks (Q3W) dosing intervals.; Drug: 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.; Other Names: PHST001 + paclitaxel, PHST001 + topotecan, PHST001 + doxorubicin, PHST001 + gemcitabine, PHST001 + FOLFIRI, or PHST001 + FOLFOX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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	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	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	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.	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.	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.	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.	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.	From screening and during treatment up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	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)	Defined as time from date of first objective response (either CR or PR) to first documentation of radiographic disease progression.	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)	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.	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).	Defined as the maximum blood concentration of a dose of PHST001	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)	Defined as the time required for a dose of PHST001 to reach its maximum blood concentration (Cmax) after administration.	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)	Defined as the blood concentration of a dose of PHST001 at the end of the dosing interval (just prior to next drug administration).	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)	Defined as the total PHST001 exposure over time, calculated as the integral of the plasma concentration-time profile.	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)	Defined as how widely PHST001 spreads throughout the body once things have stabilized after a dose has been administered.	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)	Defined as the rate at which the body "cleans out" a dose of PHST001 from the bloodstream.	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)	Defined as the time it takes for the amount of PHST001 in the body to drop by half during the final phase of elimination.	From treatment until 90 days after last dose of PHST001
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).	Defined as the time from first dose of PHST001 to first documentation of radiographic disease progression or death, whichever occurs first.	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).	Defined as the time from first dose of PHST001 to the date of death.	From screening and during treatment up to 2 years

Collaborators and Investigators

• Sponsor: Pheast Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2025
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2031

Study Registration Dates

• First Submitted: February 10, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): February 21, 2025

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Nervous System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma; Nervous System Neoplasms; Uterine Neoplasms; Ovarian Neoplasms; Cholangiocarcinoma; Endometrial Neoplasms; Central Nervous System Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Carbohydrates; Camptothecin; Alkaloids; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Anthracyclines; Naphthacenes; Aminoglycosides; Daunorubicin; Gemcitabine; Doxorubicin; Paclitaxel; Topotecan; Folfox protocol
• Other Study ID Numbers: PHST001-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No