Clinical Trials /

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

NCT03894618

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Anal Canal Squamous Cell Carcinoma
  • Cervical Squamous Cell Carcinoma
  • Diffuse Large B-Cell Lymphoma
  • Gastric Adenocarcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hodgkin Lymphoma
  • Malignant Solid Tumor
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
  • Skin Squamous Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: SL01-DEL-101
  • NCT ID: NCT03894618

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

Interventions

DrugSynonymsArms
SL-279252SL-279252

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
SL-279252ExperimentalIntravenous administration; Two possible dosing schedules for SL-279252 may be evaluated
  • SL-279252

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description:Incidence of all treatment emergent adverse events

Secondary Outcome Measures

Measure:Establish the recommended phase 2 dose of SL-279252
Time Frame:Approximately 32 months
Safety Issue:
Description:Establish the recommended phase 2 dose of SL-279252
Measure:Overall Response Rate of SL-279252
Time Frame:Approximately 32 months
Safety Issue:
Description: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
Measure:Immunogenicity to SL-279252
Time Frame:Approximately 32 months
Safety Issue:
Description:Number and proportion of participants with positive anti-drug antibody titer
Measure:Maximum serum concentration (Cmax) of SL-279252
Time Frame:Approximately 32 months
Safety Issue:
Description:The Cmax is the maximum observed serum concentration of SL-279252 following single and multiple doses
Measure:Minimum serum concentration (Cmin) of SL-279252
Time Frame:Approximately 32 months
Safety Issue:
Description:The Cmin is the minimum observed serum concentration of SL-279252 following single and multiple doses
Measure:Time at which maximum concentration of SL-279252 is observed (Tmax)
Time Frame:Approximately 32 months
Safety Issue:
Description:The Tmax is the time at which the maximum concentration of SL-279252 is observed following single and multiple doses
Measure:Area under the serum concentration-time curve (AUC)
Time Frame:Approximately 32 months
Safety Issue:
Description:The AUC is the area under the serum concentration time curve following single and multiple doses of SL-279252
Measure:Terminal half life (t1/2)
Time Frame:Approximately 32 months
Safety Issue:
Description:The t1/2 elimination half-life of SL-279252
Measure:Clearance
Time Frame:Approximately 32 months
Safety Issue:
Description:Clearance of SL-279252
Measure:Volume of distribution
Time Frame:Approximately 32 months
Safety Issue:
Description:Volume of distribution of SL-279252

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Shattuck Labs, Inc.

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