Clinical Trials /

Sym021 in Combination With Either Sym022 or Sym023 in Patients With Advanced Solid Tumor Malignancies

NCT04641871

Description:

This study will evaluate the preliminary efficacy of the 2 combinations (Sym021+Sym022 and Sym021+Sym023) in each tumor type under study by assessing ORRs per Investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. This study will also evaluate the safety and tolerability profile of the 2 combinations (Sym021+Sym022 and Sym021+Sym023)

Related Conditions:
  • Cholangiocarcinoma
  • Endometrial Carcinoma
  • Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Sym021 in Combination With Either Sym022 or Sym023 in Patients With Advanced Solid Tumor Malignancies
  • Official Title: An Exploratory, Open-label, Multicenter Phase 1b Trial to Evaluate Safety and Efficacy of Sym021 (Anti-PD-1) in Combination With Either Sym022 (Anti-LAG-3) or Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies

Clinical Trial IDs

  • ORG STUDY ID: Sym021-02
  • NCT ID: NCT04641871

Conditions

  • Metastatic Cancer
  • Solid Tumor

Interventions

DrugSynonymsArms
Sym021Anti-PD-1Sym021+Sym022 [ARM A]
Sym022Anti-LAG-3Sym021+Sym022 [ARM A]
Sym023Anti-TIM-3Sym021+Sym023 [ARM B]

Purpose

This study will evaluate the preliminary efficacy of the 2 combinations (Sym021+Sym022 and Sym021+Sym023) in each tumor type under study by assessing ORRs per Investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. This study will also evaluate the safety and tolerability profile of the 2 combinations (Sym021+Sym022 and Sym021+Sym023)

Detailed Description

      The study will evaluate safety and efficacy in participant with small cell lung cancer,
      urothelial cancer and bladder cancer who have developed resistance to prior anti-PD1 or
      anti-PD-L1 therapy and in patient with cholangiocarcinoma who have received at least 1 line
      of standard of care therapy and have progressed on it
    

Trial Arms

NameTypeDescriptionInterventions
Sym021+Sym022 [ARM A]ExperimentalSym021 will be infused over approximately 30 minutes (+10 minutes), followed by a 30-minute post-dosing interval before infusion of Sym022 over approximately 30 minutes (+10 minutes). The duration of each infusion may be extended by 30 minutes, or longer, if indicated.
  • Sym021
  • Sym022
Sym021+Sym023 [ARM B]ExperimentalSym021 will be infused over approximately 30 minutes (+10 minutes), followed by a 30-minute post-dosing interval before infusion of Sym023 over approximately 30 minutes (+10 minutes). The duration of each infusion may be extended by 30 minutes, or longer, if indicated.
  • Sym021
  • Sym023

Eligibility Criteria

        Inclusion Criteria:

        Patients must meet all the following criteria to be eligible for participation in the
        study:

          -  Male or female patients, ≥18 years.

          -  Patients with documented (histologically or cytologically proven) unresectable,
             locally advanced, or metastatic malignancies:

               1. Urothelial cancer (UC)

               2. Small cell lung cancer (SCLC)

               3. Endometrial cancer (EC) of any histological subtype

               4. Cholangiocarcinoma (CCA): unresectable or metastatic adenocarcinoma of the intra-
                  and/or extra-hepatic bile ducts

          -  Patients with UC, SCLC, and EC must have received prior anti-PD-(L)1 therapy with a
             best response of CR/PR or durable SD

          -  Patients with measurable disease according to RECIST v1.1

          -  Patients with an ECOG PS of 0 or 1, and anticipated life expectancy of ≥3 months

          -  Patients must have adequate organ function as indicated by laboratory values

          -  Adequate contraception required as appropriate

        Exclusion Criteria:

          -  Has central nervous system (CNS) malignancies

          -  Patients with significant cardiovascular disease

          -  Patients with

               1. Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism,
                  within 4 weeks prior to the first study drug dose

               2. Active uncontrolled bleeding or a known bleeding diathesis

          -  Patients with a significant pulmonary disease or condition

          -  Patients with a current or recent (within 6 months) significant gastrointestinal
             disease or condition

          -  Patients with a significant ocular disease or condition

          -  Patients with an active, known or suspected autoimmune disease

          -  Patients with any other serious/active/uncontrolled infection

          -  Prior therapy with anti-LAG-3 or anti-TIM-3 or combinations of these 2 antibodies with
             anti-PD-(L)1 antibody or with any other systemic or localized therapy

          -  Patients with a history of significant toxicities associated with previous
             administration of immune checkpoint inhibitors that necessitated permanent
             discontinuation of that therapy

          -  Patients with a known or suspected hypersensitivity to any of the excipients of
             formulated study drug

          -  Patients with unresolved >Grade 1 toxicity associated with any prior antineoplastic
             therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To evaluate the preliminary efficacy of the 2 combinations (Sym021+Sym022 and Sym021+Sym023) in each tumor type under study by assessing ORRs per Investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame:Until disease progression or end of study, whichever comes first, assessed up to 24 months
Safety Issue:
Description:Objective Response Rate (ORR) per Investigator assessment of antitumor activity (based on radiological evidence per RECIST v1.1)

Secondary Outcome Measures

Measure:Peak Plasma Concentration (Cmax) of the 2 combinations (Sym021+Sym022 and Sym021+Sym023)
Time Frame:First dose of study drug
Safety Issue:
Description:Peak Plasma Concentration (Cmax) for first dose of each drug in each combination. Will be derived from observed data
Measure:To confirm the RP2D of each combination
Time Frame:36 month
Safety Issue:
Description:Confirmation of the RP2D, based on the dose-response relationship (in case more than one dose level is implemented), overall tolerability and safety profile, and the PK and pharmacodynamic data
Measure:Evaluation of duration of response.
Time Frame:Until disease progression or end of study, whichever comes first, assessed up to 24 months
Safety Issue:
Description:Will be calculated from the day the initial response is observed to the day progression of disease is observed
Measure:To evaluate the immunogenicity of each drug in the combinations
Time Frame:From screening up to 30 month
Safety Issue:
Description:Occurrence of ADA measured in serum at selected timepoints during the study
Measure:Area under the plasma concentration versus time curve (AUC) of the 2 combinations (Sym021+Sym022 and Sym021+Sym023)
Time Frame:First study drug dose
Safety Issue:
Description:Area under the plasma concentration versus time curve (AUC) for first dose of each drug in each combination. Will be estimated using non-compartmental methods and actual time points
Measure:Time to reach maximum concentration (Tmax) of the 2 combinations (Sym021+Sym022 and Sym021+Sym023)
Time Frame:First study drug dose
Safety Issue:
Description:Time to reach maximum concentration (Tmax) for first dose of each drug in each combination. Will be derived from observed data.
Measure:Trough concentration (Ctrough) of the 2 combinations (Sym021+Sym022 and Sym021+Sym023)
Time Frame:First dose of study drug
Safety Issue:
Description:Trough concentration (Ctrough) for first dose of each drug in each combination. Will be derived from observed data.
Measure:Evaluation of Progression-Free Survival (PFS) (the PFS rate at 6 months will additionally be evaluated in patients with SCLC)
Time Frame:From first study drug dose until disease progression or end of study, whichever comes first, assessed up to 24 months
Safety Issue:
Description:Will be calculated as from the first study drug dose to the day progression of disease is confirmed radiological or date of death.
Measure:Evaluation of Disease Control Rate (DCR), defined as CR, PR, or stable disease (SD) ≥6 months
Time Frame:Until disease progression or end of study, whichever comes first, assessed up to 6 months
Safety Issue:
Description:Will be calculated according to standard response criteria
Measure:Evaluation of Objective Response Rate (ORR) per Investigator assessment (based on Immunotherapeutics Response Evaluation Criteria in Solid Tumors [iRECIST])
Time Frame:Until disease progression or end of study, whichever comes first, assessed up to 24 months
Safety Issue:
Description:Will be based on Investigators assessment on Immunotherapeutic Response Evaluation Criteria in Solid Tumors (iRECIST)
Measure:Evaluation Overall Survival (OS)
Time Frame:From first dose of study drug until death or latest survival follow-up assessed up to 30 month
Safety Issue:
Description:Overall survival will be derived from start of treatment until death or latest survival follow-up.

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
  • Anti-LAG-3
  • LAG-3
  • LAG3
  • Anti-TIM-3
  • TIM-3
  • TIM3
  • Urothelial cancer
  • UC
  • Small Cell Lung Cancer
  • SCLC
  • Endometrial cancer
  • EC
  • Cholangiocarcinoma
  • CCA

Last Updated

November 24, 2020