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
Status: Recruiting
Location: See all (20) locations...
Intervention Type: Drug, Biological
Study Type: Interventional
Study Phase: Phase 1
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 anticancer therapies (Phase 1b) in adult participants with advanced relapsed and/or refractory solid tumors (including but not limited to CNS tumors in Phase 1a only). Phase 1b will include the following cohorts 1) tumor-specific cohorts for participants with advanced relapsed and/or refractory ovarian cancer, endometrial cancer, and cholangiocarcinoma, 2) a randomized cohort for participants with ovarian cancer who will receive PHST001 in combination with mirvetuximab soravtansine, 3) a cohort for participants with advanced/metastatic breast cancer who will receive PHST001 in combination with trastuzumab deruxtecan and 4) a cohort of patients who consent to additional biomarker studies. The study's primary objectives are to evaluate the safety and tolerability of PHST001 and determine the RP2D (Recommended Phase 2 dose) of PHST001 as monotherapy and in combination with anticancer therapies, as well as to assess the anti-tumor activity of PHST001 in combination with anticancer therapies in Phase 1b.
Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:
• 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
Locations
United States
California
Precision NextGen Oncology & Research Center
RECRUITING
Beverly Hills
USC Norris Comprehensive Cancer Center
RECRUITING
Los Angeles
Stanford University School of Medicine
RECRUITING
Palo Alto
Colorado
Sarah Cannon Research Institute (SCRI) Oncology Partners - Denver Health One
RECRUITING
Denver
Connecticut
Yale Cancer Center
RECRUITING
New Haven
Illinois
University of Chicago Medical Center
RECRUITING
Chicago
Massachusetts
Dana Farber Cancer Institute
RECRUITING
Boston
Michigan
University of Michigan Rogel Cancer Center
RECRUITING
Ann Arbor
START Center for Cancer Research - Midwest
RECRUITING
Grand Rapids
North Carolina
Duke Cancer Institute
RECRUITING
Durham
New York
START Center for Cancer Research - Long Island New York
RECRUITING
Lake Success
Mount Sinai
RECRUITING
New York
Tennessee
Sarah Cannon Research Institute (SCRI) Oncology Partners
RECRUITING
Nashville
Vanderbilt-Ingram Cancer Center
RECRUITING
Nashville
Texas
START Center for Cancer Research - Texas
RECRUITING
Fort Worth
MD Anderson Cancer Center
RECRUITING
Houston
NEXT Oncology - Dallas
RECRUITING
Irving
START Center for Cancer Research - San Antonio
RECRUITING
San Antonio
University of Texas (UT) Health
RECRUITING
San Antonio
Virginia
NEXT Oncology - Virginia
RECRUITING
Fairfax
Contact Information
Primary
Raphaël Rousseau, Chief Medical Officer, PhD, MD
medical@pheast.com
650-260-8443
Time Frame
Start Date:2025-03-31
Estimated Completion Date:2031-04
Participants
Target number of participants:426
Treatments
Experimental: PHST001 Monotherapy
Participants will receive PHST001 monotherapy administered once every 3 weeks (Q3W). In Phase 1a, PHST001 will be evaluated in sequential dose-escalation cohorts at planned dose levels of 0.1, 0.3, 1.0, 2.0, 4.0, 6.0, 9.0, 18.0, and 36.0 mg/kg. Dose levels may be modified or additional dose levels evaluated based on emerging safety, pharmacokinetic, pharmacodynamic, and antitumor activity data. Participants in the Phase 1b biomarker cohort may also receive PHST001 monotherapy.
Experimental: PHST001 + Paclitaxel
Participants will receive PHST001 in combination with paclitaxel. The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in tumor-specific expansion cohorts, including participants with ovarian carcinoma, endometrial carcinoma, or cholangiocarcinoma, and/or in the biomarker cohort.
Experimental: PHST001 + Topotecan
Participants will receive PHST001 in combination with topotecan. The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in the ovarian carcinoma expansion cohort and/or biomarker cohort.
Experimental: PHST001 + Doxorubicin
Participants will receive PHST001 in combination with doxorubicin. The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in ovarian carcinoma or endometrial carcinoma expansion cohorts and/or the biomarker cohort.
Experimental: PHST001 + FOLFIRI
Participants will receive PHST001 in combination with FOLFIRI (5-fluorouracil, folinic acid, and irinotecan). The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in the cholangiocarcinoma expansion cohort and/or biomarker cohort.
Experimental: PHST001 + FOLFOX
Participants will receive PHST001 in combination with FOLFOX (5-fluorouracil, folinic acid, and oxaliplatin). The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in the cholangiocarcinoma expansion cohort and/or biomarker cohort.
Experimental: PHST001 + Gemcitabine
Participants will receive PHST001 in combination with gemcitabine. The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in ovarian carcinoma or cholangiocarcinoma expansion cohorts and/or the biomarker cohort.
Experimental: PHST001 + Mirvetuximab Soravtansine
Participants will receive PHST001 in combination with mirvetuximab soravtansine. The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in the ovarian carcinoma expansion cohort and/or in the biomarker cohort. Half of the participants in the randomized ovarian carcinoma cohort may be randomly assigned to receive PHST001 in combination with mirvetuximab soravtansine.
Experimental: PHST001 + Trastuzumab Deruxtecan
Participants will receive PHST001 in combination with trastuzumab deruxtecan. The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in participants with advanced or metastatic breast cancer and/or in the biomarker cohort.
Participants with ovarian carcinoma enrolled in the randomized Phase 1b expansion cohort will be randomized 1:1 to receive mirvetuximab soravtansine monotherapy or mirvetuximab soravtansine in combination with PHST001. Participants assigned to this arm will receive mirvetuximab soravtansine monotherapy.