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

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ClinicalTrials.gov Identifier: NCT03894618
Recruitment Status : Recruiting
First Posted : March 28, 2019
Last Update Posted : June 11, 2019
Sponsor:
Information provided by (Responsible Party):
Shattuck Labs, Inc.

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.

Condition or disease Intervention/treatment Phase
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 Drug: SL-279252 Phase 1

Detailed Description:
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. The study design consists of Dose Escalation and Dose Expansion Cohorts. In the dose escalation phase of the study, subjects will be enrolled into sequential dose levels. During dose escalation, two possible schedules for administration of SL-279252 may be explored. The MTD or MAD may be determined for either schedule. Based on accumulating data from the dose escalation phase, including safety, PK, pharmacodynamic and anti-tumor activity, up to two dose expansion cohorts may be opened. The primary objective of the expansion phase is to further refine the safety and tolerability of SL-279252. The expansion cohorts will evaluate one or two doses of SL-279252 using one selected schedule. At the end of dose escalation and dose expansion, safety, PK, anti-tumor activity, and pharmacodynamic data will be reviewed to identify the RP2D.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 87 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Dose Escalation and Dose Expansion Study of an Agonist Redirected Checkpoint Fusion Protein, SL-279252 (PD1-Fc-OX40L), in Subjects With Advanced Solid Tumors or Lymphomas
Actual Study Start Date : March 26, 2019
Estimated Primary Completion Date : February 2, 2022
Estimated Study Completion Date : April 5, 2022


Arm Intervention/treatment
Experimental: SL-279252
Intravenous administration; Two possible dosing schedules for SL-279252 may be evaluated
Drug: SL-279252
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).




Primary Outcome Measures :
  1. Safety profile of SL-279252 - Incidence of all treatment emergent adverse events [ Time Frame: From Day 1 to 90 days after Last Dose of SL-279252 (approximately 1 year) ]
    Incidence of all treatment emergent adverse events

  2. Maximum Tolerated Dose (MTD) of SL-279252 [ Time Frame: From Day 1 to 90 days after Last Dose of SL-279252 (approximately 1 year) ]
    Defined based on the rate of dose limiting toxicities (DLTs)


Secondary Outcome Measures :
  1. Establish the recommended phase 2 dose of SL-279252 [ Time Frame: Approximately 32 months ]
    Establish the recommended phase 2 dose of SL-279252

  2. Overall Response Rate of SL-279252 [ Time Frame: Approximately 32 months ]

    Response assessment according to immune response evaluation criteria in solid tumors (iRECIST) for solid tumors or response evaluation criteria in lymphoma (RECIL) 2017 for lymphomas

    • Objective response rate (ORR; proportion of participants whose best overall response is a complete response [CR] or partial response [PR] evaluated via iRECIST.
    • Clinical benefit rate (CBR; proportion of participants whose best overall response is an iCR, iPR or stable disease (iSD) of >12 weeks); minor response (MR) will be included for lymphomas

  3. Immunogenicity to SL-279252 [ Time Frame: Approximately 32 months ]
    Number and proportion of participants with positive anti-drug antibody titer

  4. Maximum serum concentration (Cmax) of SL-279252 [ Time Frame: Approximately 32 months ]
    The Cmax is the maximum observed serum concentration of SL-279252 following single and multiple doses

  5. Minimum serum concentration (Cmin) of SL-279252 [ Time Frame: Approximately 32 months ]
    The Cmin is the minimum observed serum concentration of SL-279252 following single and multiple doses

  6. Time at which maximum concentration of SL-279252 is observed (Tmax) [ Time Frame: Approximately 32 months ]
    The Tmax is the time at which the maximum concentration of SL-279252 is observed following single and multiple doses

  7. Area under the serum concentration-time curve (AUC) [ Time Frame: Approximately 32 months ]
    The AUC is the area under the serum concentration time curve following single and multiple doses of SL-279252

  8. Terminal half life (t1/2) [ Time Frame: Approximately 32 months ]
    The t1/2 elimination half-life of SL-279252

  9. Clearance [ Time Frame: Approximately 32 months ]
    Clearance of SL-279252

  10. Volume of distribution [ Time Frame: Approximately 32 months ]
    Volume of distribution of SL-279252



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 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, diffuse large B cell 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.
  3. 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.
  4. Age 18 years and older.
  5. Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
  6. Has measurable disease by iRECIST (solid tumors) or RECIL 2017 (lymphoma).
  7. Has life expectancy of greater than 12 weeks.
  8. Has adequate organ function.
  9. Females of child bearing potential (FCBP) must have a negative serum or urine pregnancy test within 72 hours of D1 of IP.
  10. Male subjects with female partners must have azoospermia from a prior vasectomy or underlying medical condition or agree to use an acceptable method of contraception during treatment and for 30 days.
  11. All AEs resulting from prior anti-cancer immunotherapy have resolved.
  12. Recovery from toxicities from prior anti-cancer treatments including surgery, radiotherapy, chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade 1.

Exclusion Criteria:

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

  1. Has received more than two prior checkpoint inhibitor containing treatment regimens (regimen refers to either monotherapy or combination immunotherapies).
  2. Refractory to last checkpoint inhibitor therapy defined as disease progression within 3 months of treatment initiation.
  3. Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy is prohibited.
  4. Use of corticosteroids or other immunosuppressive medication, current or within 14 days of D1 of IP.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03894618


Contacts
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Contact: Lini Pandite, M.D. 984-329-5231 lpandite@shattucklabs.com
Contact: Fatima Rangwala, M.D., Ph.D. 984-329-5231 frangwala@shattucklabs.com

Locations
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United States, Tennessee
The Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Melissa L Johnson, MD       Melissa.Johnson@sarahcannon.com   
Principal Investigator: Melissa L Johnson, MD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: David S Hong, MD       dshong@mdanderson.org   
Principal Investigator: David S. Hong, MD         
Canada, Ontario
Princess Margaret Cancer Center Active, not recruiting
Toronto, Ontario, Canada, M5G 1Z5
Sponsors and Collaborators
Shattuck Labs, Inc.
Investigators
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Study Director: Shattuck Labs Shattuck Labs

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Responsible Party: Shattuck Labs, Inc.
ClinicalTrials.gov Identifier: NCT03894618     History of Changes
Other Study ID Numbers: SL01-DEL-101
First Posted: March 28, 2019    Key Record Dates
Last Update Posted: June 11, 2019
Last Verified: April 2019

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

Additional relevant MeSH terms:
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Lymphoma
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Adenocarcinoma
Lymphoma, B-Cell
Hodgkin Disease
Carcinoma, Renal Cell
Lymphoma, Large B-Cell, Diffuse
Carcinoma, Transitional Cell
Squamous Cell Carcinoma of Head and Neck
Esophageal Neoplasms
Anus Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Glandular and Epithelial
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Squamous Cell
Lymphoma, Non-Hodgkin