Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Sym024 Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies

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: NCT04672434
Recruitment Status : Recruiting
First Posted : December 17, 2020
Last Update Posted : July 2, 2021
Sponsor:
Information provided by (Responsible Party):
Symphogen A/S

Tracking Information
First Submitted Date  ICMJE December 7, 2020
First Posted Date  ICMJE December 17, 2020
Last Update Posted Date July 2, 2021
Actual Study Start Date  ICMJE November 19, 2020
Estimated Primary Completion Date March 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 16, 2020)
  • Part I: To evaluate the incidence, severity and relationship of (S)AEs to establish the MTD/MAD of Sym024 monotherapy. [ Time Frame: 28 days ]
    Assess the safety and tolerability of Sym024 monotherapy on a Q2W schedule (every two weeks). Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1
  • Part II: To evaluate the incidence, severity and relationship of (S)AEs to establish MTD/MAD of Sym024 in combination with Sym021. [ Time Frame: 28 days ]
    Assess the safety and tolerability of the sequential escalating doses of Sym024 in combination with Sym021 on a Q2W schedule. Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1
  • Part III: To evaluate the incidence, severity and relationship of (S)AEs to further assess safety of Sym024 when administered alone or in combination with Sym021. [ Time Frame: 12 months ]
    Assess the safety and tolerability of Sym024 and/or Sym021+Sym024 on a Q2W schedule. Assessment based on the occurrence of AEs
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2020)
  • Evaluation of the immunogenicity of Sym024 as a single agent and in combination with Sym024 [ Time Frame: 24 months ]
    Serum sampling to assess the potential for anti-drug antibody (ADA) formation
  • Evaluation of objective response (OR) or stable disease (SD) [ Time Frame: 24 months ]
    Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) and Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST)
  • Time to progression (TTP) of disease [ Time Frame: 24 months ]
    Based on time of enrollment to first evidence of progression on imaging studies, as assessed by RECIST v1.1 and iRECIST
  • Area under the concentration-time curve in a dosing interval (AUC) [ Time Frame: 24 months ]
    Will be estimated using non-compartmental methods and actual timepoints
  • Maximum concentration (Cmax) [ Time Frame: 24 months ]
    Will be derived from observed data
  • Time to reach maximum concentration (Tmax) [ Time Frame: 24 months ]
    Will be derived from observed data
  • Trough concentration (Ctrough) [ Time Frame: 24 months ]
    Will be derived from observed data
  • Terminal elimination half-life (T½) [ Time Frame: 24 months ]
    Will be estimated using non-compartmental methods and actual timepoints
  • Clearance (CL) [ Time Frame: 24 months ]
    Will be estimated using non-compartmental methods and actual timepoints
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 Sym024 Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies
Official Title  ICMJE A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym024 (Anti-CD73) as Monotherapy and in Combination With Sym021 (Anti-PD-1) in Patients With Advanced Solid Tumor Malignancies
Brief Summary The primary purpose of this study is to see if Sym024 is safe and tolerable as monotherapy and in combination with Sym021 in patients with solid tumor malignancies.
Detailed Description

Part 1 of this study will assess the safety and tolerability to establish the maximum tolerated dose (MTD) (or the maximum administered dose [MAD]) and/or the selected dose(s) of Sym024 in patients with solid tumor malignancies.

Part 2 of this study will assess the safety and tolerability to establish the MTD (or the MAD) and/or the selected dose(s) of Sym024 when administered in combination with Sym021 in patients with solid tumor malignancies.

Part 3 of this study will assess the safety of Sym024 when administered alone or in combination with Sym021 in expanded cohorts of patients with solid tumor malignancies.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Cancer
  • Solid Tumor
Intervention  ICMJE
  • Drug: Sym021
    Sym021 is a humanized anti-PD-1 antibody.
    Other Name: Anti-PD-1
  • Drug: Sym024
    Sym024 is an anti-CD73 antibody.
Study Arms  ICMJE
  • Experimental: Sym024 Dose Level 1
    Part I, Sym024 monotherapy dose level 1
    Intervention: Drug: Sym024
  • Experimental: Sym024 Dose Level 2
    Part I, Sym024 monotherapy dose level 2
    Intervention: Drug: Sym024
  • Experimental: Sym024 Dose Level 3
    Part I, Sym024 monotherapy dose level 3
    Intervention: Drug: Sym024
  • Experimental: Sym024 Dose Level 4
    Part I, Sym024 monotherapy dose level 4
    Intervention: Drug: Sym024
  • Experimental: Sym024 Dose Level -1
    Part I, Sym024 monotherapy dose level -1. Evaluate only if needed based on tolerability
    Intervention: Drug: Sym024
  • Experimental: Sym021+Sym024 Dose Level 2
    Part II, Sym021 in combination with dose level 2 of Sym024
    Interventions:
    • Drug: Sym021
    • Drug: Sym024
  • Experimental: Sym021+Sym024 Dose Level 3
    Part II, Sym021 in combination with dose level 3 of Sym024
    Interventions:
    • Drug: Sym021
    • Drug: Sym024
  • Experimental: Sym021+Sym024 Dose Level 4
    Part II, Sym021 in combination with dose level 4 of Sym024
    Interventions:
    • Drug: Sym021
    • Drug: Sym024
  • Experimental: Sym021+Sym024 Dose Level 1
    Part II, Sym021 in combination with dose level 1 of Sym024. Evaluate only if needed based on tolerability
    Interventions:
    • Drug: Sym021
    • Drug: Sym024
  • Experimental: Dose Expansion Sym021 (+Sym024)
    Part III, dose expansion Sym024 and/or Sym021+Sym024
    Interventions:
    • Drug: Sym021
    • Drug: Sym024
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: December 16, 2020)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2024
Estimated Primary Completion Date March 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female patients, ≥18 years.
  • Documented (histologically or cytologically proven), locally advanced or metastatic solid tumor malignancy (must be one of the following):

    1. Squamous cell carcinoma of the head and neck
    2. Non-small-cell lung carcinoma-adenocarcinoma histology subtype
    3. Pancreatic ductal adenocarcinoma
    4. Cholangiocarcinoma
    5. Colorectal carcinoma (microsatellite stable [MSS] and microsatellite instability-high [MSI-H] phenotypes)
    6. Gastric carcinoma (includes gastroesophageal carcinoma)
    7. Esophageal carcinoma (includes squamous cell and adenocarcinoma)
    8. Mesothelioma (pleural and peritoneal)
  • Malignancy that is not currently amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
  • Measurable disease according to RECIST v1.1.
  • Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
  • Agreeing to mandatory tumor tissue biopsies (2 total).
  • ECOG PS of 0 or 1.
  • Adequate organ function as indicated by the following laboratory values.
  • Adequate contraception required as appropriate.

Exclusion Criteria:

  • Central nervous system (CNS) malignancies.
  • Clinically significant cardiovascular disease or condition.
  • Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism within 4 weeks prior to the first dose of study drug(s).
  • Active uncontrolled bleeding or a known bleeding diathesis.
  • Significant ocular disease or condition.
  • Significant pulmonary disease or condition.
  • Current or recent (within 6 months) significant gastrointestinal disease or condition.
  • Active, known or suspected autoimmune disease.
  • History of organ transplantation (i.e., stem cell or solid organ transplant).
  • Known history of human immunodeficiency virus (HIV) or known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
  • Any other serious/active/uncontrolled infection.
  • History of significant toxicities associated with previous administration of immune checkpoint inhibitors.
  • Known or suspected hypersensitivity to any of the excipients of formulated study drug.
  • Unresolved >Grade 1 toxicity associated with any prior antineoplastic therapy.
  • Inadequate recovery from any prior surgical procedure, or patients having undergone any major surgical procedure within 4 weeks prior to the first dose of study drug(s).
  • Any other serious, life-threatening, or unstable preexisting medical condition (aside from the underlying malignancy).

Therapeutic Exclusions

  • Prior therapy with Sym024 or other inhibitors of CD73, CD39 or adenosine receptors ADORA2A, ADORA2B.
  • Part II and Part III, prior anti-PD-(L)1 therapy, except for indications where it is approved.
  • Any antineoplastic agent for the primary malignancy (standard or investigational) within 4 weeks or 5 elimination half-lives.
  • Any other investigational treatments within 2 weeks prior to the first dose of study drug(s).
  • Radiotherapy, with exceptions.
  • Live vaccines against infectious diseases 4 weeks prior to the first dose of study drug(s).
  • Immunosuppressive or systemic glucocorticoids therapy (>10 mg daily prednisone or equivalent) within 2 weeks prior to the first dose of study drug(s), with exceptions.
  • Prophylactic use of hematopoietic growth factors within 1 week prior to the first dose of study drug(s).
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: U. Hansen +45 45265050 info@symphogen.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04672434
Other Study ID Numbers  ICMJE Sym024-01
Has Data Monitoring Committee No
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
Plan to Share IPD: No
Responsible Party Symphogen A/S
Study Sponsor  ICMJE Symphogen A/S
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: N. Lakhani, MD PhD START Midwest, USA
PRS Account Symphogen A/S
Verification Date July 2021

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