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Sym021 in Combination With Either Sym022 or Sym023 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: NCT04641871
Recruitment Status : Recruiting
First Posted : November 24, 2020
Last Update Posted : December 31, 2020
Sponsor:
Information provided by (Responsible Party):
Symphogen A/S

Brief Summary:
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)

Condition or disease Intervention/treatment Phase
Metastatic Cancer Solid Tumor Drug: Sym021 Drug: Sym022 Drug: Sym023 Phase 1

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.

Per 22nd of December 2020 recruitment for small cell lung cancer, urothelial cancer and bladder cancer has temporarily stopped due to strategy considerations. Recruitment for cholangiocarcinoma is still open.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 12, 2020
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sym021+Sym022 [ARM A]
Sym021 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.
Drug: Sym021
IV infusion over 30 minutes on day 1 and 15 of each cycle.
Other Name: Anti-PD-1

Drug: Sym022
IV infusion over 30 minutes on day 1 and 15 of each cycle.
Other Name: Anti-LAG-3

Experimental: Sym021+Sym023 [ARM B]
Sym021 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.
Drug: Sym021
IV infusion over 30 minutes on day 1 and 15 of each cycle.
Other Name: Anti-PD-1

Drug: Sym023
IV infusion over 30 minutes on day 1 and 15 of each cycle.
Other Name: Anti-TIM-3




Primary Outcome Measures :
  1. 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 ]
    Objective Response Rate (ORR) per Investigator assessment of antitumor activity (based on radiological evidence per RECIST v1.1)

  2. To evaluate the incidence, severity, and relationship of (S)AEs collected from administration of the first dose of study drug until 30 days after the last dose of the 2 combinations (Sym021+Sym022 and Sym021+Sym023) [ Time Frame: Through study completion up to 30 days after last dose of the two combinations ]
    Calculation of AE incidence will be based on the number of patients per AE category; AEs in total and sorted by frequency, AEs by relationship, SAEs in total and by relationship, Immune mediated AEs, Fatal AEs

  3. To evaluate the AEs leading to dose interruption, dose delays, and permanent treatment stop of the 2 combinations (Sym021+Sym022 and Sym021+Sym023) [ Time Frame: Through study completion up to a maximum of 12 months ]
    Calculation of AE incidence will be based on the number of patients per AE category ; AEs leading to dose interruption, dose delays, and permanent treatment stop


Secondary Outcome Measures :
  1. Peak Plasma Concentration (Cmax) of the 2 combinations (Sym021+Sym022 and Sym021+Sym023) [ Time Frame: First dose of study drug ]
    Peak Plasma Concentration (Cmax) for first dose of each drug in each combination. Will be derived from observed data

  2. To confirm the RP2D of each combination [ Time Frame: 36 month ]
    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

  3. Evaluation of duration of response. [ Time Frame: Until disease progression or end of study, whichever comes first, assessed up to 24 months ]
    Will be calculated from the day the initial response is observed to the day progression of disease is observed

  4. To evaluate the immunogenicity of each drug in the combinations [ Time Frame: From screening up to 30 month ]
    Occurrence of ADA measured in serum at selected timepoints during the study

  5. Area under the plasma concentration versus time curve (AUC) of the 2 combinations (Sym021+Sym022 and Sym021+Sym023) [ Time Frame: First study drug dose ]
    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

  6. Time to reach maximum concentration (Tmax) of the 2 combinations (Sym021+Sym022 and Sym021+Sym023) [ Time Frame: First study drug dose ]
    Time to reach maximum concentration (Tmax) for first dose of each drug in each combination. Will be derived from observed data.

  7. Trough concentration (Ctrough) of the 2 combinations (Sym021+Sym022 and Sym021+Sym023) [ Time Frame: First dose of study drug ]
    Trough concentration (Ctrough) for first dose of each drug in each combination. Will be derived from observed data.

  8. 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 ]
    Will be calculated as from the first study drug dose to the day progression of disease is confirmed radiological or date of death.

  9. 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 ]
    Will be calculated according to standard response criteria

  10. 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 ]
    Will be based on Investigators assessment on Immunotherapeutic Response Evaluation Criteria in Solid Tumors (iRECIST)

  11. Evaluation Overall Survival (OS) [ Time Frame: From first dose of study drug until death or latest survival follow-up assessed up to 30 month ]
    Overall survival will be derived from start of treatment until death or latest survival follow-up.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04641871


Contacts
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Contact: Helle Rudbaek, RN +45 88382625 heru@symphogen.com

Locations
Show Show 28 study locations
Sponsors and Collaborators
Symphogen A/S
Investigators
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Principal Investigator: Nehal Lakhani, MD START Midwest
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Responsible Party: Symphogen A/S
ClinicalTrials.gov Identifier: NCT04641871    
Other Study ID Numbers: Sym021-02
First Posted: November 24, 2020    Key Record Dates
Last Update Posted: December 31, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Symphogen A/S:
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
Additional relevant MeSH terms:
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Neoplasms
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes