A Study of PHST001 in Advanced Solid Tumors

NCT06840886 | Recruiting Phase 1 FDA Drug

• 1 other identifier: PHST001-101
• Study Type: interventional
• Target: 272
• Locations: 1 country
• Sites: 20

Brief 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.

Conditions

Advanced Solid Tumors; Ovarian Cancer; Endometrial Cancer; Cholangiocarcinoma; CNS Tumor

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (12)

• 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)

  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)

  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)

  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).

  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).

  From screening and during treatment up to 2 years

Study Arms (2)

Dose Escalation (Phase 1a)

EXPERIMENTAL

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

Dose Expansion (Phase 1b)

EXPERIMENTAL

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; Drug: Chemotherapy per Standard of Care

Interventions

PHST001 BIOLOGICAL

PHST001 is an anti-CD24 macrophage checkpoint inhibitor, administered as IV infusions every 3-weeks (Q3W) dosing intervals.

Dose Escalation (Phase 1a); Dose Expansion (Phase 1b)

Chemotherapy per Standard of Care DRUG

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.

Also known as: PHST001 + paclitaxel, PHST001 + topotecan, PHST001 + doxorubicin, PHST001 + gemcitabine, PHST001 + FOLFIRI, or PHST001 + FOLFOX

Dose Expansion (Phase 1b)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pheast Therapeutics: lead

Study Sites (20)

Precision NextGen Oncology & Research Center

Beverly Hills, California, 90212, United States

NOT YET RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

Stanford University School of Medicine

Palo Alto, California, 94304, United States

RECRUITING

Sarah Cannon Research Institute (SCRI) Oncology Partners - Denver Health One

Denver, Colorado, 80218, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06520, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

START Center for Cancer Research - Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

START Center for Cancer Research - Long Island New York

Lake Success, New York, 11042, United States

RECRUITING

Mount Sinai

New York, New York, 10029, United States

NOT YET RECRUITING

Duke Cancer Institute

Durham, North Carolina, 27710, United States

RECRUITING

Sarah Cannon Research Institute (SCRI) Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37203, United States

RECRUITING

START Center for Cancer Research - Texas

Fort Worth, Texas, 76104, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Oncology - Dallas

Irving, Texas, 75039, United States

RECRUITING

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229, United States

RECRUITING

University of Texas (UT) Health

San Antonio, Texas, 78229, United States

NOT YET RECRUITING

NEXT Oncology - Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Endometrial Neoplasms; Cholangiocarcinoma; Central Nervous System Neoplasms

Interventions

Paclitaxel; Topotecan; Doxorubicin; Gemcitabine; Folfox protocol

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Nervous System Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Camptothecin; Alkaloids; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Andrew Ferguson/VP Clinical Development, PhD

CONTACT

434-249-2349; medical@pheast.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose levels are 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, 36.0 mg/kg alone or in combination with chemotherapy

Study Record Dates

• First Submitted: February 10, 2025
• First Posted: February 21, 2025
• Study Start: March 31, 2025
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2031
• Last Updated: May 14, 2026

Record last verified: 2026-05

Locations

US (20)