A Study of PHST001 in Advanced Solid Tumors

Phase 1RecruitingNCT06840886

Pheast Therapeutics272 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

272

Conditions

Advanced Solid Tumors Ovarian Cancer Endometrial Cancer Cholangiocarcinoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (20)

Precision NextGen Oncology & Research Center

Beverly Hills, California, United States

NOT_YET_RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

RECRUITING

Stanford University School of Medicine

Palo Alto, California, United States

RECRUITING

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

Denver, Colorado, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

RECRUITING

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, United States

RECRUITING

START Center for Cancer Research - Midwest

Grand Rapids, Michigan, United States

RECRUITING

START Center for Cancer Research - Long Island New York

Lake Success, New York, United States

RECRUITING

...and 10 more locations

Outcomes

Primary Outcomes

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.