Trial Title:
Phase 1b Study of SL-172154 Administered with Combination Agent(s) in Subjects with Ovarian Cancers
NCT ID:
NCT05483933
Condition:
Platinum-resistant Ovarian Cancer
Fallopian Tube Cancer
Epithelial Ovarian Cancer
Ovarian Cancer
Platinum-Resistant Fallopian Tube Carcinoma
Platinum-Resistant Primary Peritoneal Carcinoma
Primary Peritoneal Carcinoma
Conditions: Official terms:
Carcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Doxorubicin
Liposomal doxorubicin
Conditions: Keywords:
Platinum-resistant
Ovarian
Peritoneal
High grade serous EOC
primary peritoneal cancer
Fallopian
Combination
Mirvetuximab Soravtansine
SL-172154
SIRPα-Fc-CD40L
Pegylated Liposomal Doxorubicin
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Active, not recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pegylated Liposomal Doxorubicin + SL-172154
Description:
The investigational product, SL-172154, is a novel fusion protein consisting of human
SIRPα and CD40L (SIRPα -Fc-CD40L) linked via a human Fc.
Arm group label:
Pegylated Liposomal Doxorubicin + SL-172154 (SIRPα-Fc-CD40L)
Other name:
Doxil
Other name:
PLD
Other name:
Caelyx
Intervention type:
Drug
Intervention name:
Mirvetuximab + SL-172154
Description:
The investigational product, SL-172154, is a novel fusion protein consisting of human
SIRPα and CD40L (SIRPα -Fc-CD40L) linked via a human Fc.
Arm group label:
Mirvetuximab + SL-172154 (SIRPα-Fc-CD40L)
Other name:
IMGN853
Other name:
MIRV
Summary:
SL03-OHD-105 is an open-label, multicenter, phase 1b trial designed to evaluate SL-172154
administered in combination with pegylated liposomal doxorubicin (PLD) or mirvetuximab
soravtansine (MIRV) in patients with platinum resistant ovarian cancer. Approximately 102
patients will be enrolled in this study in two phases: dose escalation and dose
expansion.
Detailed description:
Study SL03-OHD-105 is an open-label, multicenter, phase 1b trial designed to evaluate the
safety, pharmacokinetics, pharmacodynamic effects, and preliminary anti-tumor activity of
SL-172154 administered in combination with either PLD or MIRV in subjects with
platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers. Patients will
be appropriate for combination therapy for their next line of therapy. For the SL-172154
+ MIRV cohort, patients' tumors must be positive (defined as PS2+ ≥ 25%) for folate
receptor alpha (FRα) as defined by the Ventana FOLR1 (Folate Receptor 1/Folate Receptor
Alpha) Assay.
The first portion of the study will evaluate the safety of increasing dose levels of
SL-172154 in combination with either PLD or MIRV and establish a combination dose for
both regimens to be further evaluated in two dose expansion cohorts. The study will
consist of a 21-day screening period, a study treatment period until at least one of the
study treatment discontinuation criteria is met, and a study follow-up period.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Subject has voluntarily agreed to participate by giving written informed consent in
accordance with ICH/GCP guidelines and applicable local regulations.
2. Age ≥18 years
3. [PLD Cohort] Subject has a histologically confirmed diagnosis of high grade
epithelial ovarian cancer, including primary peritoneal cancer or fallopian tube
cancer. Non-epithelial tumors and ovarian tumors with low malignant potential are
excluded.
4. [PLD Cohort] Subject must have platinum-resistant disease, defined as radiologic
disease progression within 180 days (6 months) following the last administered dose
of platinum therapy. Subjects who are primary platinum-refractory, defined by
progressing during or within 1 month of upfront platinum therapy, are excluded.
5. [PLD Cohort] Subjects may have received any number of prior lines of therapy for
epithelial ovarian cancer; however, they may not have received more than 1 prior
line of systemic anticancer therapy for platinum-resistant disease.
6. [MIRV Cohort] Subject has a histologically confirmed diagnosis of high grade serous
epithelial ovarian cancer, including primary peritoneal cancer or fallopian tube
cancer. Non-epithelial tumors and ovarian tumors with low malignant potential are
excluded.
7. [MIRV Cohort] Subject must have platinum-resistant disease as defined by:
- Subjects who have only had 1 line of platinum-based therapy must have received
at least 4 cycles of platinum, must have had a response (complete
response/remission [CR] or partial response/remission [PR]) and then progressed
between >3 months and ≤6 months after the date of the last dose of platinum.
- Subjects who have received 2 or 3 lines of platinum therapy must have
progressed on or within 6 months after the date of the last dose of platinum.
- Subjects who are platinum refractory during front-line treatment are excluded
[primary platinum-refractory disease, defined as disease that did not respond
to (CR or PR) or has progressed within 3 months of the last dose of first-line
platinum-containing chemotherapy]
8. [MIRV Cohort] Subjects must have received at least 1 but no more than 3 prior
systemic lines of anticancer therapy.
9. [MIRV Cohort] Willing to provide an archival tumor tissue block or slides or undergo
procedure to obtain new biopsy using a low-risk, medically routine procedure for IHC
confirmation of FRα positivity.
10. [MIRV Cohort] Subject's tumor must be positive for FRα expression (defined as PS2+ ≥
25% by the Ventana FOLR1 Assay).
11. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
12. Measurable disease by RECIST v1.1 using radiologic assessment.
13. Adequate organ and hematologic function
14. Subjects must have stabilized or recovered (Grade 1 or baseline) from all prior
anti-cancer therapy-related toxicities.
15. [MIRV Cohort, Dose Expansion only] Willing to consent to 1 mandatory pre-treatment
and 1 on-treatment tumor biopsy, unless there is excessive risk from the procedure
as determined by the investigator
Exclusion Criteria:
1. Prior treatment with a signal-regulatory protein alpha (SIRPα) targeting agent,
anti-CD47 agent or CD40 agonist.
2. [PLD Cohort] Prior treatment with doxorubicin or PLD
3. [MIRV Cohort] Prior treatment with MIRV or another FRα-targeting agent
4. Any anti-cancer therapy within the time intervals specified per protocol.
5. Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer
treatment is prohibited.
6. Receipt of live attenuated vaccine (including live attenuated vaccines for COVID-19)
within 28 days of the first dose of study treatment.
7. Current or prior use of systemic immunosuppressive medication within 7 days prior to
first dose of study treatment.
8. [MIRV Cohort] Requires use of folate-containing supplements (e.g., folate
deficiency)
9. Active or documented history of autoimmune disease that has required treatment with
a disease modifying agent or immunosuppressive therapy in the past two years,
history of multiple sclerosis (MS) or other demyelinating disease and/or
Lambert-Eaton syndrome (paraneoplastic syndrome). Exceptions include controlled Type
I diabetes, vitiligo, alopecia areata or hypo/hyperthyroidism.
10. Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment
of infection within 5 days of D1 of study treatment).
11. Known severe hypersensitivity to the active drug substance or to any of the
excipients for the agents to be administered or known hypersensitivity to Chinese
hamster ovary cell products.
12. Severe gastrointestinal conditions.
13. Clinically significant or uncontrolled cardiovascular disease
14. [MIRV Cohort] History of cirrhotic liver disease (Child-Pugh Class B or C)
15. [MIRV Cohort] Active or chronic corneal disorders, history of corneal
transplantation, or active ocular conditions requiring ongoing treatment/monitoring,
such as uncontrolled glaucoma, wet age-related macular degeneration requiring
intravitreal injections, active diabetic retinopathy with macular edema, macular
degeneration, presence of papilledema, and/or monocular vision.
16. Previous clinical diagnosis of noninfectious interstitial lung disease (ILD),
including noninfectious pneumonia.
17. Untreated central nervous system or leptomeningeal metastases.
18. Another malignancy that requires active therapy and that, in the opinion of the
investigator and Sponsor, would interfere with monitoring of radiologic assessments
of response to the study treatment.
19. Has undergone allogeneic stem cell transplantation or organ transplantation.
20. Known history or positive test for human immunodeficiency virus (HIV), or positive
test for hepatitis B (positive for hepatitis B surface antigen [HBsAg]) or hepatitis
C virus ([HCV]
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Arkansas for Medical sciences
Address:
City:
Little Rock
Zip:
72205
Country:
United States
Facility:
Name:
City of Hope
Address:
City:
Duarte
Zip:
91010
Country:
United States
Facility:
Name:
Robert H.Lurie ComprehensiveCancer Center, Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Facility:
Name:
START Midwest
Address:
City:
Grand Rapids
Zip:
49546
Country:
United States
Facility:
Name:
Stephenson Cancer Center, OU Health/ Sarah Cannon Research Institute
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Facility:
Name:
BC Cancer Center
Address:
City:
Vancouver
Zip:
BC V5Z 4E6
Country:
Canada
Facility:
Name:
University health Network (UHN)-University of Toronto
Address:
City:
Toronto
Zip:
M5G 2M9
Country:
Canada
Facility:
Name:
McGill University Health Care
Address:
City:
Montréal
Zip:
H4A 3J1
Country:
Canada
Facility:
Name:
Hospital Universitari Germans Trias i Pujol
Address:
City:
Badalona
Zip:
08916
Country:
Spain
Facility:
Name:
Hospital Clinic de Barcelona Servicio de Oncología, Esc. 2, Planta 5 dcha
Address:
City:
Barcelona
Zip:
08036
Country:
Spain
Facility:
Name:
Hospital Universitario Quirón-Dexeus Servicio de Oncologia Médica
Address:
City:
Barcelona
Zip:
08028
Country:
Spain
Facility:
Name:
Hospital Universitario Dr. Josep Trueta - ICO de Girona, Servicio de Oncología Av. Francia s/n
Address:
City:
Girona
Zip:
17007
Country:
Spain
Facility:
Name:
Hospital Universitari Vall D Hebron
Address:
City:
Madrid
Zip:
28013
Country:
Spain
Facility:
Name:
Hospital Universitario Fundacion Jimenez Diaz START Madrid-FJD- Unidad de Ensayos Fase I
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Facility:
Name:
Hospital Universitario Virgen de la Arrixaca. Servicio de Oncología Ctra. Madrid-Cartagena, s/n
Address:
City:
Murcia
Zip:
30120
Country:
Spain
Facility:
Name:
Lancashire Teaching Hospitals NHS Foundation Trust
Address:
City:
Preston
Zip:
PR2 9HT
Country:
United Kingdom
Facility:
Name:
Guy's & St Thomas' NHS Foundation Trust
Address:
City:
London
Zip:
SE1 7EH
Country:
United Kingdom
Facility:
Name:
The Royal Marsden NHS Foundation Trust
Address:
City:
London
Zip:
SW3 6JJ
Country:
United Kingdom
Facility:
Name:
University College London Hospitals NHS Foundation Trust
Address:
City:
London
Zip:
W1T 7HA
Country:
United Kingdom
Facility:
Name:
The Royal Marsden NHS Foundation Trust
Address:
City:
Sutton
Zip:
SM2 5PT
Country:
United Kingdom
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Start date:
August 18, 2022
Completion date:
November 2024
Lead sponsor:
Agency:
Shattuck Labs, Inc.
Agency class:
Industry
Source:
Shattuck Labs, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05483933
