A Study of PHST001 in Advanced Solid Tumors
Purpose
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
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- 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
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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. |
|
|
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. |
|
Recruiting Locations
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee 37203
Nashville, Tennessee 37203
More Details
- Status
- Recruiting
- Sponsor
- Pheast Therapeutics