A Study of PHST001 in Advanced Solid Tumors

Official title

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

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.

Interventions

• 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.

Primary outcome measures

• 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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [Time frame: From screening and during treatment up to 2 years]

Secondary outcome measures (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) [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

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

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 20 centers

• Precision NextGen Oncology & Research Center — Beverly Hills
• USC Norris Comprehensive Cancer Center — Los Angeles
• Stanford University School of Medicine — Palo Alto
• Sarah Cannon Research Institute (SCRI) Oncology Partners - Denver Health One — Denver
• Yale Cancer Center — New Haven
• University of Chicago Medical Center — Chicago
• Dana Farber Cancer Institute — Boston
• University of Michigan Rogel Cancer Center — Ann Arbor
• … and 12 more centers

Identifiers

NCT: NCT06840886 · PHST001-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗