Phase 1b Study of SL-172154 Administered With Combination Agent(s) in Subjects With Ovarian Cancers

Ovarian Cancer Clinical Trial

Official title:

An Open-Label, Phase 1b Study of SL-172154 (SIRPα-Fc-CD40L) Administered With Either Pegylated Liposomal Doxorubicin or Mirvetuximab Soravtansine in Subjects With Platinum-Resistant Ovarian Cancers

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05483933
• Other study ID #: SL03-OHD-105
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 18, 2022
• Est. completion date: April 2025

Study information

• Verified date: May 2024
• Source: Shattuck Labs, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 86
• Est. completion date: April 2025
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 FRa positivity.

10. [MIRV Cohort] Subject's tumor must be positive for FRa 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 (SIRPa) 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 FRa-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]

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Ovarian Epithelial
• Epithelial Ovarian Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Platinum-Resistant Fallopian Tube Carcinoma
• Platinum-resistant Ovarian Cancer
• Platinum-Resistant Primary Peritoneal Carcinoma
• Primary Peritoneal Carcinoma

Intervention

Drug:
• Pegylated Liposomal Doxorubicin + SL-172154
The investigational product, SL-172154, is a novel fusion protein consisting of human SIRPa and CD40L (SIRPa -Fc-CD40L) linked via a human Fc.
• Mirvetuximab + SL-172154
The investigational product, SL-172154, is a novel fusion protein consisting of human SIRPa and CD40L (SIRPa -Fc-CD40L) linked via a human Fc.

Locations

Country	Name	City	State
Canada	McGill University Health Care	Montréal	Quebec
Canada	University health Network (UHN)-University of Toronto	Toronto	Ontario
Canada	BC Cancer Center	Vancouver	British Columbia
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona Servicio de Oncología, Esc. 2, Planta 5 dcha	Barcelona	Catalunya
Spain	Hospital Universitario Quirón-Dexeus Servicio de Oncologia Médica	Barcelona
Spain	Hospital Universitario Dr. Josep Trueta - ICO de Girona, Servicio de Oncología Av. Francia s/n	Girona
Spain	Hospital Universitari Vall D Hebron	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz START Madrid-FJD- Unidad de Ensayos Fase I	Madrid
Spain	Hospital Universitario Virgen de la Arrixaca. Servicio de Oncología Ctra. Madrid-Cartagena, s/n	Murcia
United Kingdom	Guy's & St Thomas' NHS Foundation Trust	London	London, City Of
United Kingdom	The Royal Marsden NHS Foundation Trust	London	London, City Of
United Kingdom	University College London Hospitals NHS Foundation Trust	London	London, City Of
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Lancashire Teaching Hospitals NHS Foundation Trust	Preston	Lancashire
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton	London, City Of
United States	Robert H.Lurie ComprehensiveCancer Center, Northwestern University	Chicago	Illinois
United States	City of Hope	Duarte	California
United States	START Midwest	Grand Rapids	Michigan
United States	University of Arkansas for Medical sciences	Little Rock	Arkansas
United States	Stephenson Cancer Center, OU Health/ Sarah Cannon Research Institute	Oklahoma City	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Shattuck Labs, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate safety and tolerability of SL-172154 when administered with PLD	Incidence and severity of adverse events (AE) per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0	first dose up to 3 years
Primary	Evaluate safety and tolerability of SL-172154 when administered with MIRV	Incidence and severity of adverse events (AE) per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0	first dose up to 3 years
Primary	Establish the recommended Phase 2 dose (RP2D) for SL-172154 when administered with PLD	Establish the recommended Phase 2 dose (RP2D) for SL-172154 when administered with PLD for the dose expansion phase	first dose up to 1 year
Primary	Establish the recommended Phase 2 dose (RP2D) for SL-172154 when administered with MIRV	Establish the recommended Phase 2 dose (RP2D) for SL-172154 when administered with MIRV for the dose expansion phase	first dose up to 1 year
Secondary	To assess preliminary evidence of anti-tumor activity of SL-172154 when administered with PLD	Overall response rate per investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)	first dose up to 3 years
Secondary	To assess preliminary evidence of anti-tumor activity of SL-172154 when administered with MIRV	Overall response rate per investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)	first dose up to 3 years
Secondary	Immunogenicity to SL-172154	Number and proportion of participants with positive anti-drug antibody titer	first dose up to 3 years
Secondary	Immunogenicity to MIRV	Number and proportion of participants with positive anti-drug antibody titer	first dose up to 3 years
Secondary	Maximum serum concentration (Cmax) of SL-172154	The Cmax is the maximum observed serum concentration of SL-172154 following single and multiple doses	first dose up to 3 years
Secondary	Maximum serum concentration (Cmax) of MIRV	The Cmax is the maximum observed serum concentration of MIRV following single and multiple doses	first dose up to 3 years
Secondary	Maximum serum concentration (Cmax) of Total Antibody	The Cmax is the maximum observed serum concentration of Total Antibody following single and multiple doses	first dose up to 3 years
Secondary	Maximum serum concentration (Cmax) of DM4 Payload	The Cmax is the maximum observed serum concentration of DM4 Payload following single and multiple doses	first dose up to 3 years
Secondary	Maximum serum concentration (Cmax) of S-Methyl DM4 Payload	The Cmax is the maximum observed serum concentration of S-Methyl DM4 Payload following single and multiple doses	first dose up to 3 years
Secondary	Area under the serum concentration-time curve (AUC) of SL-172154	The AUC is the area under the serum concentration time curve of SL-172154 following single and multiple doses	first dose up to 3 years
Secondary	Area under the serum concentration-time curve (AUC) of MIRV	The AUC is the area under the serum concentration time curve of MIRV following single and multiple doses	first dose up to 3 years
Secondary	Area under the serum concentration-time curve (AUC) of Total Antibody	The AUC is the area under the serum concentration time curve of Total Antibody following single and multiple doses	first dose up to 3 years
Secondary	Area under the serum concentration-time curve (AUC) of DM4 Payload	The AUC is the area under the serum concentration time curve of DM4 Payload following single and multiple doses	first dose up to 3 years
Secondary	Area under the serum concentration-time curve (AUC) of S-Methyl DM4 Payload	The AUC is the area under the serum concentration time curve of S-Methyl DM4 Payload following single and multiple doses	first dose up to 3 years
Secondary	Terminal elimination half-life (t1/2) of SL-172154	Terminal elimination half-life (t1/2) of SL-172154	first dose up to 3 years
Secondary	Terminal elimination half-life (t1/2) of MIRV	Terminal elimination half-life (t1/2) of MIRV	first dose up to 3 years
Secondary	Terminal elimination half-life (t1/2) of Total Antibody	Terminal elimination half-life (t1/2) of Total Antibody	first dose up to 3 years
Secondary	Terminal elimination half-life (t1/2) of DM4 Payload	Terminal elimination half-life (t1/2) of DM4 Payload	first dose up to 3 years
Secondary	Terminal elimination half-life (t1/2) of S-Methyl DM4 Payload	Terminal elimination half-life (t1/2) of S-Methyl DM4 Payload	first dose up to 3 years