Trial Title:
A Phase 1-2 of ST316 With Selected Advanced Unresectable and Metastatic Solid Tumors
NCT ID:
NCT05848739
Condition:
Colon Cancer
Metastatic Colon Cancer
Conditions: Official terms:
Colonic Neoplasms
Bevacizumab
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
ST316
Description:
IV
Arm group label:
Dose Escalation Phase
Arm group label:
ST316 & FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase
Arm group label:
ST316 & Fruquintinib Combination CRC Expansion phase
Arm group label:
ST316 & Lonsurf + Bevacizumab Combination CRC Expansion phase
Arm group label:
ST316 Monotherapy Colon Rectal Cancer (CRC) Expansion phase
Intervention type:
Drug
Intervention name:
FOLFIRI regimen & bevacizumab
Description:
FOLFIRI: Days 1 and 15 of each 28-day cycle:
- irinotecan 180 mg/m2 IV over 90 minutes concurrently with
- leucovorin 400 mg/m2 IV over 2 hours, and then
- 5-FU bolus 400mg/m2 (up to 15 min infusion)
- 5-FU 2400 mg/m2 IV over 46 hours
- bevacizumab should be administered as 5mg/kg.
Arm group label:
ST316 & FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase
Other name:
FOLFIRI
Intervention type:
Drug
Intervention name:
Fruquintinib
Description:
5 mg once a day for the first 21 days of a 28-day cycle
Arm group label:
ST316 & Fruquintinib Combination CRC Expansion phase
Intervention type:
Drug
Intervention name:
Lonsurf & bevacizumab
Description:
Lonsurf 35 mg/m2 twice daily on days 1-5 and days 8-12 every 28 day bevacizumab 5 mg/kg
on days 1 and 15. ST316
Arm group label:
ST316 & Lonsurf + Bevacizumab Combination CRC Expansion phase
Summary:
This is an open-label, two-part, phase 1-2 study designed to determine the safety,
tolerability, PK, pharmacodynamics (PD), and proof-of-concept efficacy of ST316
administered IV in subjects with selected advanced solid tumors likely to harbor
abnormalities of the WNT/β-catenin signaling pathway. The study consists of two phases: a
phase 1 dose escalation/regimen exploration phase and a phase 2 expansion phase.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Able and willing to sign an informed consent form (ICF) and comply with the protocol
and the restrictions and assessments therein.
2. Male or female ≥18 years of age.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
4. Must have a locally advanced or metastatic inoperable tumor as follows:
1. For the dose-escalation phase: CRC, HCC, TNBC, NSCLC, OC, melanoma, CCA, and
SS.
2. For the expansion phase: CRC. Note: if additional indications and combinations
are added inclusion/exclusion criteria will be updated.
5. Agrees to provide a newly obtained biopsy of an accessible lesion (if they can be
biopsied based on the Investigator's assessment) prior to the start of study
treatment, and to repeat biopsy once during study treatment. Tissue obtained for the
biopsy must not be previously irradiated, but a new or progressing lesion in the
radiation field is acceptable. Subjects without accessible lesion for biopsy must be
able to provide an archival tumor tissue sample for central lab analysis.
6. In the Investigator's opinion, the subject may not derive clinical benefit from, or
is ineligible for, a particular form of standard therapy on medical grounds, or the
subject failed or did not tolerate one or more of other anticancer therapies:
a. For the dose escalation phase: i. Refractory, intolerant, or refused available
standard-of-care therapies. ii. Up to three previous lines of systemic anticancer
therapies for metastatic disease are allowed (adjuvant or neoadjuvant setting do not
count as lines of systemic therapy).
iii. Subjects with TNBC or OC with known BRCA mutations must have been previously treated
with or intolerant to Food and Drug Administration (FDA) approved treatments prior to
enrolling in this study (e.g., iPARP).
iv. Subjects with OC must have been treated with, refused, or were ineligible for
treatment with bevacizumab to enroll.
v. Subjects with CRC tumors that are MSI-H/dMMR must have received, refused or be
intolerant to a checkpoint inhibitor (CPI).
vi. Subjects with HCC must have confirmed diagnosis of inoperable hepatocellular
carcinoma by histology or clinical/radiological criteria. No more than two prior lines of
systemic therapy only and Child Pugh Score A or B7.
b. For the expansion phase: i. For all cohorts: Subjects with MSI-H/dMMR must have
received, refused or be intolerant to a CPI.
ii. Cohort 1 ST316 monotherapy: CRC that has progressed after or on treatment with all of
the following, alone or in combination, comprising a maximum of four prior lines of
therapy for their advanced/metastatic disease: oxaliplatin, irinotecan,
fluoropyrimidines, anti-vascular-endothelial growth factor (VEGF), anti-epidermal growth
factor receptor (EGFR) targeted agents (as indicated).
iii. Cohort 2: Combination with standard of care (SOC) FOLFIRI + bevacizumab: CRC that
has progressed after or on treatment with all of the following, alone or in combination,
comprising a maximum of one prior line of therapy for their advanced/metastatic disease:
oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF. Subjects with RAS wild-type must
have been treated with an anti-EGFR targeted agent during the first line of treatment.
iv. Cohort 3: Combination with fruquintinib: CRC that has progressed after or on
treatment with all of the following, alone or in combination, comprising a maximum of two
prior lines of therapy for their advanced/metastatic disease: oxaliplatin, irinotecan,
fluoropyrimidines or anti-VEGF Subjects with RAS wild-type must have been treated with an
anti-EGFR targeted agent during the first or second line of treatment.
v. Cohort 4: Combination with Lonsurf + beva: CRC that has progressed after or on
treatment with all of the following, alone or in combination, comprising a maximum of two
prior lines of therapy for their advanced/metastatic disease: oxaliplatin, irinotecan,
fluoropyrimidines or anti-VEGF Subjects with RAS wild-type must have been treated with an
anti-EGFR targeted agent during the first or second line of treatment.
Exclusion Criteria:
1. Known hypersensitivity to ST316 or any of its excipients.
2. Known hypersensitivity to bevacizumab, 5-FU, leucovorin or irinotecan for Cohort 2,
to fruquintinib for Cohort 3 and trifluridine or tipiracil for Cohort 4 in the
expansion.
3. Corrected interval between Q and T wave on electrocardiogram (ECG) (QTc) > 480 msec
using Fredericia's formula.
4. Symptomatic ascites or pleural effusion. A subject who is clinically stable for 4
weeks following treatment for these conditions (including therapeutic thoraco- or
paracentesis) is eligible.
5. Known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate
provided they are clinically stable for at least 2 weeks prior to study entry and
have no evidence of new or enlarging brain metastases. Subjects with treated brain
metastases must also follow the steroid exclusion criterion (#11) listed below.
6. For expansion phase only: presence of any other active malignancy requiring systemic
therapy other than the disease under study.
7. For subjects to be treated with a regimen containing bevacizumab:
1. History of cardiac disease: congestive heart failure (CHF) ≥NYHA Class II;
active coronary artery disease, myocardial infarction within 6 months prior to
study entry; unevaluated new onset angina within 3 months or unstable angina
(angina symptoms at rest) or cardiac arrhythmias requiring anti-arrhythmic
therapy (βeta blockers or digoxin are permitted).
2. Current uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg or
diastolic pressure >90 mmHg despite optimal medical management) as well as
prior history of hypertensive crisis or hypertensive encephalopathy.
3. History of arterial thrombotic or embolic events (within 6 months prior to
study entry).
4. Significant vascular disease (e.g., aortic aneurysm, aortic dissection,
symptomatic peripheral vascular disease).
5. Evidence of bleeding diathesis or clinically significant coagulopathy.
6. Major surgical procedure (including open biopsy, significant traumatic injury,
etc.) within 28 days, or anticipation of the need for major surgical procedure
during the course of the study as well as minor surgical procedure (excluding
placement of a vascular access device or bone marrow biopsy) within 7 days
prior to study enrollment.
7. Proteinuria at screening as demonstrated by urinalysis with proteinuria ≥2+
(subjects discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline
should undergo a 24-hour urine collection and must demonstrate ≤1g of protein
in 24 hours to be eligible).
8. History of abdominal fistula, gastrointestinal perforation, peptic ulcer, or
intraabdominal abscess within 6 months.
9. Ongoing serious, non-healing wound, ulcer, or bone fracture.
10. History of reversible posterior leukoencephalopathy syndrome (RPLS).
11. History of hypersensitivity to Chinese hamster ovary (CHO) cells or other human
or humanized recombinant antibodies.
-
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
USC Norris Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Status:
Recruiting
Contact:
Last name:
Stephanie Kim
Email:
Stephanie.Kim2@med.usc.edu
Investigator:
Last name:
Anthoney El-Khoueiry, MD
Email:
Principal Investigator
Facility:
Name:
Sarah Cannon Research Institute - CO
Address:
City:
Denver
Zip:
80218
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tamara Davidson, MD
Email:
Tamara.Davidson@sarahcannon.com
Investigator:
Last name:
Jason Henry, MD
Email:
Principal Investigator
Facility:
Name:
Ochsner Clinic Foundation
Address:
City:
New Orleans
Zip:
70123
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nicole Perry
Investigator:
Last name:
Jonathan Mizrahi, MD
Email:
Principal Investigator
Facility:
Name:
START Midwest
Address:
City:
Grand Rapids
Zip:
49503
Country:
United States
Status:
Recruiting
Contact:
Last name:
Julie Burns, BSN
Email:
Julie.Burns@startmidwest.com
Investigator:
Last name:
Nehal Lakhani, MD
Email:
Principal Investigator
Facility:
Name:
Duke Universtiy
Address:
City:
Durham
Zip:
27708
Country:
United States
Status:
Recruiting
Contact:
Last name:
JoAnna Gontarz, MSN
Email:
joanna.gontarz@duke.edu
Investigator:
Last name:
Niharika Mettu, MD PhD
Email:
Principal Investigator
Facility:
Name:
OU Health Stephenson Cancer Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christina Caldwell
Email:
Christina.Caldwell@ouhealth.com
Investigator:
Last name:
Susanna Ulahannan, MD
Email:
Principal Investigator
Facility:
Name:
Sanford Cancer Center
Address:
City:
Sioux Falls
Zip:
57104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Staci Vogel
Phone:
605-312-3320
Email:
staci.vogel@sanfordhealth.org
Investigator:
Last name:
Steven Powell, MD
Email:
Principal Investigator
Start date:
June 5, 2023
Completion date:
May 31, 2027
Lead sponsor:
Agency:
Sapience Therapeutics
Agency class:
Industry
Source:
Sapience Therapeutics
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05848739
