Clinical Trials /

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

NCT04672434

Description:

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.

Related Conditions:
  • Cholangiocarcinoma
  • Colorectal Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Lung Adenocarcinoma
  • Mesothelioma
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Sym024 Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: Sym024-01
  • NCT ID: NCT04672434

Conditions

  • Metastatic Cancer
  • Solid Tumor

Interventions

DrugSynonymsArms
Sym021Anti-PD-1Dose Expansion Sym021 (+Sym024)
Sym024Dose Expansion Sym021 (+Sym024)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Sym024 Dose Level 1ExperimentalPart I, Sym024 monotherapy dose level 1
  • Sym024
Sym024 Dose Level 2ExperimentalPart I, Sym024 monotherapy dose level 2
  • Sym024
Sym024 Dose Level 3ExperimentalPart I, Sym024 monotherapy dose level 3
  • Sym024
Sym024 Dose Level 4ExperimentalPart I, Sym024 monotherapy dose level 4
  • Sym024
Sym024 Dose Level -1ExperimentalPart I, Sym024 monotherapy dose level -1. Evaluate only if needed based on tolerability
  • Sym024
Sym021+Sym024 Dose Level 2ExperimentalPart II, Sym021 in combination with dose level 2 of Sym024
  • Sym021
  • Sym024
Sym021+Sym024 Dose Level 3ExperimentalPart II, Sym021 in combination with dose level 3 of Sym024
  • Sym021
  • Sym024
Sym021+Sym024 Dose Level 4ExperimentalPart II, Sym021 in combination with dose level 4 of Sym024
  • Sym021
  • Sym024
Sym021+Sym024 Dose Level 1ExperimentalPart II, Sym021 in combination with dose level 1 of Sym024. Evaluate only if needed based on tolerability
  • Sym021
  • Sym024
Dose Expansion Sym021 (+Sym024)ExperimentalPart III, dose expansion Sym024 and/or Sym021+Sym024
  • Sym021
  • Sym024

Eligibility Criteria

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

Primary Outcome Measures

Measure:Part I: To evaluate the incidence, severity and relationship of (S)AEs to establish the MTD/MAD of Sym024 monotherapy.
Time Frame:28 days
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Evaluation of the immunogenicity of Sym024 as a single agent and in combination with Sym024
Time Frame:24 months
Safety Issue:
Description:Serum sampling to assess the potential for anti-drug antibody (ADA) formation
Measure:Evaluation of objective response (OR) or stable disease (SD)
Time Frame:24 months
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) and Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST)
Measure:Time to progression (TTP) of disease
Time Frame:24 months
Safety Issue:
Description:Based on time of enrollment to first evidence of progression on imaging studies, as assessed by RECIST v1.1 and iRECIST
Measure:Area under the concentration-time curve in a dosing interval (AUC)
Time Frame:24 months
Safety Issue:
Description:Will be estimated using non-compartmental methods and actual timepoints
Measure:Maximum concentration (Cmax)
Time Frame:24 months
Safety Issue:
Description:Will be derived from observed data
Measure:Time to reach maximum concentration (Tmax)
Time Frame:24 months
Safety Issue:
Description:Will be derived from observed data
Measure:Trough concentration (Ctrough)
Time Frame:24 months
Safety Issue:
Description:Will be derived from observed data
Measure:Terminal elimination half-life (T½)
Time Frame:24 months
Safety Issue:
Description:Will be estimated using non-compartmental methods and actual timepoints
Measure:Clearance (CL)
Time Frame:24 months
Safety Issue:
Description:Will be estimated using non-compartmental methods and actual timepoints

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Symphogen A/S

Trial Keywords

  • Locally advanced/unresectable
  • Metastatic solid tumor
  • Anti-PD-1
  • PD-1
  • PD1
  • CD73
  • Squamous cell carcinoma of the head and neck (SCCHN)
  • Non-small-cell lung carcinoma-adenocarcinoma histology subtype (NSCLC-Adeno)
  • Pancreatic ductal adenocarcinoma (PDAC)
  • Cholangiocarcinoma (CCA)
  • Colorectal carcinoma (CRC)
  • Gastric carcinoma (GC)
  • Esophageal carcinoma (EsoCA)
  • Mesothelioma (Meso)
  • Sym021
  • Sym024
  • Head and neck squamous cell carcinoma (HNSCC)

Last Updated

December 17, 2020