SL-279252 (PD1-Fc-OX40L) in Subjects With Advanced Solid Tumors or Lymphomas

NCT03894618 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: SL01-DEL-101
• Study Type: interventional
• Target: 49
• Locations: 4 countries
• Sites: 5

Brief Summary

This is a Phase 1 first in human, open label, multi-center, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-279252 in subjects with advanced solid tumors or lymphomas.

Conditions

Squamous Cell Carcinoma of the Head and Neck; Melanoma; Non Small Cell Lung Cancer; Urothelial Carcinoma; Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Squamous Cell Carcinoma of the Anus; Squamous Cell Carcinoma of the Cervix; Squamous Cell Carcinoma of the Skin; Renal Cell Carcinoma; Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma; Mismatch Repair Deficient or MSI-High Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Safety Profile of SL-279252

  Number of participants with treatment emergent adverse events

  From Day 1 to 90 days after Last Dose of SL-279252

• Maximum Tolerated Dose (MTD) of SL-279252

  Number of participants with dose limiting toxicities (DLTs)

  From Day 1 to Day 21 (Schedule 1) or Day 28 (Schedule 2)

Secondary Outcomes (10)

• Recommended Phase 2 Dose for SL-279252

  Approximately 32 months

• Overall Response Rate of SL-279252

  Approximately 32 months

• Immunogenicity to SL-279252

  Approximately 32 months

• Maximum Serum Concentration (Cmax) of SL-279252

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

• Minimum Serum Concentration (Cmin) of SL-279252

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

Study Arms (1)

SL-279252

EXPERIMENTAL

Intravenous administration; Two possible dosing schedules for SL-279252 may be evaluated

Drug: SL-279252

Interventions

SL-279252 DRUG

The investigational product (IP), SL-279252, is a first-in-class agonist redirected checkpoint (ARC) fusion protein (FP) consisting of the extracellular domains of human programmed cell death 1 (PD- 1) and OX40L, linked by a central Fc domain (PD1-Fc-OX40L).

SL-279252

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• 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 has a histologically confirmed diagnosis of one of the following unresectable locally advanced or metastatic malignancies: melanoma, non-small cell lung cancer (squamous, adeno, or adeno-squamous), urothelial cancer, squamous cell carcinoma of the head and neck, squamous cell cervical cancer, gastric or gastro-esophageal junction adenocarcinoma, squamous cell carcinoma of the anal canal, squamous cell carcinoma of the skin, renal cell cancer, Hodgkin's lymphoma, and microsatellite instability high (MSI-H) or mismatch repair deficient (MMRD) solid tumors excluding CNS malignancies. MSI and MMRD testing results as per institution is acceptable.
• Head and neck cancers: Subjects must have primary tumor locations in the oropharynx, oral cavity, hypopharynx, or larynx. Primary tumor sites of nasopharynx, maxillary sinus, paranasal, and unknown primary are excluded.
• Non-small cell lung cancers: Subjects with a known EGFR sensitizing (activating) mutation or an ALK fusion are excluded.
• Subject must have received, been intolerant to, or is ineligible for standard therapy (per local guidelines and approvals) or have a malignancy for which there is no approved therapy considered standard of care.
• Age 18 years and older.
• Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
• Has measurable disease by iRECIST (solid tumors) or RECIL 2017 (lymphoma). Refer to Appendix Sections 16.6 and 16.7 for details on criteria of measurable disease.
• Has life expectancy of greater than 12 weeks.
• Laboratory values must meet the following criteria. Laboratory parameter Threshold value
• Absolute lymphocyte count (ALC) ≥ 0.8 x 109/liter (L)
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without growth factor support
• Platelet count ≥ 50 x 109/L
• Laboratory parameter Threshold value

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Has received more than two prior checkpoint inhibitor containing treatment regimens (regimen refers to either monotherapy or combination immunotherapies) or has had prior treatment with an OX40 agonist.
• Prior PD-1/L1 therapy is not required.
• Refractory to last PD-1/L1 inhibitor-based therapy which is defined as disease progression within 3 months of treatment initiation.
• Subjects must have had clinical benefit (stable disease or response) to last PD-1/L1 inhibitor-based therapy for at least three months to be eligible.
• Any anti-cancer therapy within the time intervals noted below prior to first dose (D1) of SL-279252.
• Therapy Washout period Chemotherapy 3 weeks Hormonal therapy 3 weeks PD-1/L1 inhibitor and other immunotherapies not otherwise specified 3 weeks Tumor vaccine 4 weeks Cell-based therapy 8 weeks Other mAbs or biologic therapies 3 weeks Major surgery 2 weeks Radiation (except palliative intent which does not require washout) 2 weeks
• Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy 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 IP with the following exceptions (i.e., the following are allowed during treatment with or within14 days of D1 of IP):
• Topical, intranasal, inhaled, ocular, intraarticular corticosteroids
• Physiological doses of replacement steroid (e.g., for adrenal insufficiency) provided ≤ 10 mg/day of prednisone or equivalent
• Steroid premedication for hypersensitivity reactions (HSRs; e.g., reaction to IV contrast)
• Receipt of live attenuated vaccine within 28 days of D1 of IP.
• 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).

Sponsors & Collaborators

• Shattuck Labs, Inc.: lead

Study Sites (5)

The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Leuven Cancer Institute

Leuven, 3000, Belgium

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 1Z5, Canada

Location

Vall d'Hebron Institut D' Oncologia

Barcelona, 08035, Spain

Location

Related Publications (1)

• Johnson M, Hong D, Brana I, Schoffski P, Galvao V, Rangwala F, Ma B, Hernandez R, Kamat A, Kato K, Schreiber TH, Pandite L, Siu LL. First-in-human, phase 1 dose escalation study of SL-279252, a hexameric PD1-Fc-OX40L fusion protein, in patients with advanced solid tumors and lymphoma. Invest New Drugs. 2025 Apr;43(2):284-292. doi: 10.1007/s10637-025-01518-7. Epub 2025 Mar 5.

  PMID: 40042547 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Melanoma; Carcinoma, Non-Small-Cell Lung; Carcinoma, Transitional Cell; Anus Neoplasms; Carcinoma, Renal Cell; Hodgkin Disease; Lymphoma, Large B-Cell, Diffuse; Turcot syndrome

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Results Point of Contact

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

clinicaltrials@shattucklabs.com

919-864-2700

Study Officials

• Shattuck Labs

  Shattuck Labs

  STUDY DIRECTOR

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: January 10, 2019
• First Posted: March 28, 2019
• Study Start: March 26, 2019
• Primary Completion: May 4, 2023
• Study Completion: May 4, 2023
• Last Updated: April 2, 2025
• Results First Posted: March 14, 2025

Record last verified: 2025-02

Locations

BE (1); CA (1); ES (1); US (2)