Phase 1 Study of SL-172154 (SIRPα-Fc-CD40L) in Subjects With Ovarian Cancer

• ClinicalTrials.gov Identifier: NCT04406623
• Recruitment Status: Recruiting
• First Posted: May 28, 2020
• Last Update Posted: January 13, 2021
• Sponsor: Shattuck Labs, Inc.
• Information provided by (Responsible Party): Shattuck Labs, Inc.

Study Description

Brief Summary:

This is a Phase 1 first in human, open label, multi-center, dose escalation study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-172154 in subjects with ovarian cancer.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma	Drug: SL-172154	Phase 1

Detailed Description:

This Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics, anti-tumor and pharmacodynamic effects of SL-172154 and identify the dose and schedule i.e., recommended Phase 2 dose for future development (RP2D). Subjects eligible for enrollment are required to have platinum-ineligible ovarian, fallopian tube, and primary peritoneal cancers. The study design consists of dose escalation cohorts, an optional pharmacodynamic cohort, and an optional dose expansion cohort. In the dose escalation phase of the study, subjects will be enrolled into sequential dose levels. The study may also enroll a pharmacodynamic cohort to obtain additional pharmacodynamic data at one or more dose levels that have completed evaluation for safety without exceeding the maximum tolerated dose (MTD). Subjects enrolled in the pharmacodynamic cohort will not inform dose escalation decisions. A dose expansion cohort may be opened to further characterize safety, tolerability, PK, anti-tumor activity, and pharmacodynamic data to inform the selection of a RP2D.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1 Dose Escalation Study of the Agonist Redirected Checkpoint, SL-172154 (SIRPα-Fc-CD40L) Administered Intravenously in Subjects With Ovarian Cancer
• Actual Study Start Date: June 29, 2020
• Estimated Primary Completion Date: July 2022
• Estimated Study Completion Date: July 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: SL-172154; Intravenous administration	Drug: SL-172154; The investigational product (IP), SL-172154, is a novel fusion protein consisting of human SIRPα and CD40L (SIRPα -Fc-CD40L) linked via a human Fc.

Outcome Measures

Primary Outcome Measures :

1. Safety profile of SL-172154 [ Time Frame: From Day 1 to 90 days after Last Dose of SL-172154 ]
   Incidence of all treatment emergent adverse events
2. Maximum Tolerated Dose (MTD) of SL-172154 [ Time Frame: From Day 1 to 90 days after Last Dose of SL-172154 ]
   Defined based on the rate of dose limiting toxicities (DLTs)

Secondary Outcome Measures :

1. Establish the recommended Phase 2 dose (RP2D) for SL-172154 [ Time Frame: Approximately 24 months ]
   Establish the RP2D for SL-172154
2. Assess preliminary evidence of anti-tumor activity of SL-172154 [ Time Frame: Approximately 24 months ]
   Disease assessment per investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)
3. Immunogenicity to SL-172154 [ Time Frame: Approximately 24 months ]
   Number and proportion of participants with positive anti-drug antibody titer
4. Maximum serum concentration (Cmax) of SL-172154 [ Time Frame: Approximately 24 months ]
   The Cmax is the maximum observed serum concentration of SL-172154 following single and multiple doses
5. Minimum serum concentration (Cmin) of SL-172154 [ Time Frame: Approximately 24 months ]
   The Cmin is the minimum observed serum concentration of SL-172154 following single and multiple doses
6. Time at which maximum concentration of SL-172154 is observed (Tmax) [ Time Frame: Approximately 24 months ]
   The Tmax is the time at which the maximum concentration of SL-172154 is observed following single and multiple doses
7. Area under the serum concentration-time curve (AUC) [ Time Frame: Approximately 24 months ]
   The AUC is the area under the serum concentration time curve following single and multiple doses of SL-172154
8. Terminal elimination half-life (t1/2) [ Time Frame: Approximately 24 months ]
   Terminal elimination half-life (t1/2) of SL-172154
9. Clearance (CL) [ Time Frame: Approximately 24 months ]
   Clearance of Sl-172154
10. Volume of distribution [ Time Frame: Approximately 24 months ]
    Volume of distribution of SL-172154

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Participants are eligible to be included in the study only if all the following criteria apply:

1. Subject has voluntarily agreed to participate by giving written informed consent in accordance with ICH/GCP guidelines and applicable local regulations.
2. Subject must have a histologically confirmed diagnosis of an unresectable, locally advanced or metastatic ovarian cancer, or primary peritoneal cancer or fallopian tube cancer.
3. Subjects must be refractory or intolerant to existing therapy(ies) known to provide clinical benefit for their condition. Subject must have received platinum-based therapies, and should not be eligible for further platinum therapy, or should be intolerant to such therapy. Subjects with HRD positive disease may participate if they have received prior polyadenosine diphosphate ribose polymerase (PARP) inhibitor therapy given alone or with bevacizumab.
4. Subjects should not be primary platinum refractory as defined by progressing during or within 1 month of upfront platinum therapy.
5. Has measurable disease by RECIST v1.1 using radiologic assessment.
6. Subject age is 18 years and older.
7. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
8. Has life expectancy of greater than 12 weeks.
9. Has adequate organ function.
10. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test within 72 hours of D1 of IP.
11. Recovery from prior anti-cancer treatments including surgery, radiotherapy, chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade 1.
12. Willing to consent to mandatory pre-treatment and on-treatment tumor biopsy(ies), unless there is excessive risk as determined by the investigator.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

1. Prior treatment with an anti-CD47 or anti-SIRPα targeting agent or a CD40 agonist.
2. Any anti-cancer therapy within the washout period prior to first dose (D1) of SL-172154.
3. Concurrent chemotherapy, immunotherapy, biologic or hormonal/hormonal suppression therapy for cancer treatment is prohibited. Concurrent use of hormones for non-cancer related conditions is acceptable.
4. Use of corticosteroids or other immunosuppressive medication, current or within 14 days of D1 of SL-172154 treatment.
5. Receipt of live attenuated vaccine within 28 days of D1 of IP.
6. Active or documented history of autoimmune disease. Exceptions include controlled Type I diabetes, vitiligo, alopecia areata or hypo/hyperthyroidism.
7. Hypersensitivity to the active drug substance or to any of the excipients for the agent to be administered or subjects with known hypersensitivity to Chinese hamster ovary cell products.
8. Active pneumonitis (i.e. drug-induced, idiopathic pulmonary fibrosis, radiation-induced, etc.).
9. Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of infection within 5 days of D1 of IP).
10. Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious gastrointestinal disease associated with diarrhea within 6 months of D1 of IP.
11. Clinically significant or uncontrolled cardiac/thromboembolic disease.
12. Untreated central nervous system or leptomeningeal metastases.
13. Women who are breast feeding.
14. Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of AEs or compromised ability to provide written informed consent.
15. 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 IP.
16. Has undergone allogeneic stem cell transplantation or organ transplantation.
17. Known history or positive test for human immunodeficiency virus, or positive test for hepatitis B.

Contacts and Locations

Contacts

Contact: Fatima Rangwala, MD, PhD; 984-329-5231; frangwala@shattucklabs.com

Contact: Lini Pandite, MD; 984-329-5231; lpandite@shattucklabs.com

Locations

United States, California

John Wayne Cancer Institute at Providence St. John's Health Center; Recruiting

Santa Monica, California, United States, 90404

Contact: Timothy Kristedja, MD timothy.kristedja@jwci.org

United States, Michigan

START Midwest; Recruiting

Grand Rapids, Michigan, United States, 49546

Contact: Nehal Lakhani, MD, PhD Nehal.Lakhani@startmidwest.com

United States, Oklahoma

Stephenson Cancer Center at Oklahoma University; Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contact: Debra Richardson, MD Debra-Richardson@ouhsc.edu

United States, Tennessee

Sarah Cannon Research Institute; Recruiting

Nashville, Tennessee, United States, 37203

Contact: Erika Hamilton, MD ehamilton@tnonc.com

Principal Investigator: Erika Hamilton, MD

Sponsors and Collaborators

Shattuck Labs, Inc.

Investigators

• Study Director: Shattuck Labs; Shattuck Labs

More Information

• Responsible Party: Shattuck Labs, Inc.
• ClinicalTrials.gov Identifier: NCT04406623
• Other Study ID Numbers: SL03-OHD-101
• First Posted: May 28, 2020
• Last Update Posted: January 13, 2021
• Last Verified: January 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Fallopian Tube Diseases