Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03894618
Recruitment Status : Recruiting
First Posted : March 28, 2019
Last Update Posted : July 31, 2019
Sponsor:
Information provided by (Responsible Party):
Shattuck Labs, Inc.

Tracking Information
First Submitted Date  ICMJE January 10, 2019
First Posted Date  ICMJE March 28, 2019
Last Update Posted Date July 31, 2019
Actual Study Start Date  ICMJE March 26, 2019
Estimated Primary Completion Date February 2, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2019)
  • 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
  • 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)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03894618 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2019)
  • Establish the recommended phase 2 dose of SL-279252 [ Time Frame: Approximately 32 months ]
    Establish the recommended phase 2 dose of SL-279252
  • 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
  • Immunogenicity to SL-279252 [ Time Frame: Approximately 32 months ]
    Number and proportion of participants with positive anti-drug antibody titer
  • 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
  • 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
  • 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
  • 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
  • Terminal half life (t1/2) [ Time Frame: Approximately 32 months ]
    The t1/2 elimination half-life of SL-279252
  • Clearance [ Time Frame: Approximately 32 months ]
    Clearance of SL-279252
  • Volume of distribution [ Time Frame: Approximately 32 months ]
    Volume of distribution of SL-279252
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SL-279252 (PD1-Fc-OX40L) in Subjects With Advanced Solid Tumors or Lymphomas
Official Title  ICMJE 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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE 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).
Study Arms  ICMJE Experimental: SL-279252
Intravenous administration; Two possible dosing schedules for SL-279252 may be evaluated
Intervention: Drug: SL-279252
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 27, 2019)
87
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 5, 2022
Estimated Primary Completion Date February 2, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lini Pandite, M.D. 984-329-5231 lpandite@shattucklabs.com
Contact: Fatima Rangwala, M.D., Ph.D. 984-329-5231 frangwala@shattucklabs.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03894618
Other Study ID Numbers  ICMJE SL01-DEL-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Shattuck Labs, Inc.
Study Sponsor  ICMJE Shattuck Labs, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Shattuck Labs Shattuck Labs
PRS Account Shattuck Labs, Inc.
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP