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

NCT04406623 | Completed Phase 1 Results FDA Drug

• 1 other identifier: SL03-OHD-101
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 6

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.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (2)

• Safety Profile of SL-172154

  Number of participants with treatment emergent adverse events

  From Day 1 to 90 days after Last Dose of SL-172154

• Maximum Tolerated Dose (MTD) of SL-172154

  Number of participants with dose limiting toxicities (DLTs)

  From Day 1 to 90 days after Last Dose of SL-172154

Secondary Outcomes (10)

• Recommended Phase 2 Dose (RP2D) for SL-172154

  Approximately 24 months

• Assess Preliminary Evidence of Anti-tumor Activity of SL-172154

  Approximately 24 months

• Immunogenicity to SL-172154

  Approximately 24 months

• Maximum Serum Concentration (Cmax) of SL-172154

  Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days)

• Minimum Serum Concentration (Cmin) of SL-172154

  Cycle 1 Day 15 and Cycle 2 Day 1 (each cycle = 28 days)

Study Arms (1)

SL-172154

EXPERIMENTAL

Intravenous administration

Drug: SL-172154

Interventions

SL-172154 DRUG

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.

SL-172154

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all the following criteria apply:
• Subject has voluntarily agreed to participate by giving written informed consent in accordance with ICH/GCP guidelines and applicable local regulations.
• Subject must have a histologically confirmed diagnosis of an unresectable, locally advanced or metastatic ovarian cancer, or primary peritoneal cancer or fallopian tube cancer.
• 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.
• Subjects should not be primary platinum refractory as defined by progressing during or within 1 month of upfront platinum therapy.
• Has measurable disease by RECIST v1.1 using radiologic assessment.
• Subject age is 18 years and older.
• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Has life expectancy of greater than 12 weeks.
• Has adequate organ function.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test within 72 hours of D1 of IP.
• Recovery from prior anti-cancer treatments including surgery, radiotherapy, chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade 1.
• Willing to consent to mandatory pre-treatment and on-treatment tumor biopsy(ies), unless there is excessive risk as determined by the investigator.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Prior treatment with an anti-CD47 or anti-SIRPα targeting agent or a CD40 agonist.
• Any anti-cancer therapy within the washout period prior to first dose (D1) of SL-172154.
• 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.
• Use of corticosteroids or other immunosuppressive medication, current or within 14 days of D1 of SL-172154 treatment.
• Receipt of live attenuated vaccine within 28 days of D1 of IP.
• Active or documented history of autoimmune disease. Exceptions include controlled Type I diabetes, vitiligo, alopecia areata or hypo/hyperthyroidism.
• 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.
• Active pneumonitis (i.e. drug-induced, idiopathic pulmonary fibrosis, radiation-induced, etc.).
• Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of infection within 5 days of D1 of IP).
• Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious gastrointestinal disease associated with diarrhea within 6 months of D1 of IP.
• Clinically significant or uncontrolled cardiac/thromboembolic disease.
• Untreated central nervous system or leptomeningeal metastases.
• Women who are breast feeding.
• 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.

Sponsors & Collaborators

• Shattuck Labs, Inc.: lead

Study Sites (6)

City of Hope

Duarte, California, 91016, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Stephenson Cancer Center at Oklahoma University

Oklahoma City, Oklahoma, 73104, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

START Mountain Region

West Valley City, Utah, 84119, United States

Location

Related Publications (1)

• Lakhani NJ, Stewart D, Richardson DL, Dockery LE, Van Le L, Call J, Rangwala F, Wang G, Ma B, Metenou S, Huguet J, Offman E, Pandite L, Hamilton E. First-in-human phase I trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, SL-172154 in patients with platinum-resistant ovarian cancer. J Immunother Cancer. 2025 Jan 11;13(1):e010565. doi: 10.1136/jitc-2024-010565.

  PMID: 39800375 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Results Point of Contact

• Title: VP, Clinical Operations
• Organization: Shattuck Labs

clinicaltrials@shattucklabs.com

919-864-2700

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: May 28, 2020
• Study Start: June 29, 2020
• Primary Completion: February 2, 2023
• Study Completion: February 2, 2023
• Last Updated: January 30, 2025
• Results First Posted: January 30, 2025

Record last verified: 2025-01

Locations

US (6)