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

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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

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.

Condition or disease Intervention/treatment Phase
Metastatic Cancer Solid Tumor Drug: Sym021 Drug: Sym024 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 19, 2020
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2024


Arm Intervention/treatment
Experimental: Sym024 Dose Level 1
Part I, Sym024 monotherapy dose level 1
Drug: Sym024
Sym024 is an anti-CD73 antibody.

Experimental: Sym024 Dose Level 2
Part I, Sym024 monotherapy dose level 2
Drug: Sym024
Sym024 is an anti-CD73 antibody.

Experimental: Sym024 Dose Level 3
Part I, Sym024 monotherapy dose level 3
Drug: Sym024
Sym024 is an anti-CD73 antibody.

Experimental: Sym024 Dose Level 4
Part I, Sym024 monotherapy dose level 4
Drug: Sym024
Sym024 is an anti-CD73 antibody.

Experimental: Sym024 Dose Level -1
Part I, Sym024 monotherapy dose level -1. Evaluate only if needed based on tolerability
Drug: Sym024
Sym024 is an anti-CD73 antibody.

Experimental: Sym021+Sym024 Dose Level 2
Part II, Sym021 in combination with dose level 2 of Sym024
Drug: Sym021
Sym021 is a humanized anti-PD-1 antibody.
Other Name: Anti-PD-1

Drug: Sym024
Sym024 is an anti-CD73 antibody.

Experimental: Sym021+Sym024 Dose Level 3
Part II, Sym021 in combination with dose level 3 of Sym024
Drug: Sym021
Sym021 is a humanized anti-PD-1 antibody.
Other Name: Anti-PD-1

Drug: Sym024
Sym024 is an anti-CD73 antibody.

Experimental: Sym021+Sym024 Dose Level 4
Part II, Sym021 in combination with dose level 4 of Sym024
Drug: Sym021
Sym021 is a humanized anti-PD-1 antibody.
Other Name: Anti-PD-1

Drug: Sym024
Sym024 is an anti-CD73 antibody.

Experimental: Sym021+Sym024 Dose Level 1
Part II, Sym021 in combination with dose level 1 of Sym024. Evaluate only if needed based on tolerability
Drug: Sym021
Sym021 is a humanized anti-PD-1 antibody.
Other Name: Anti-PD-1

Drug: Sym024
Sym024 is an anti-CD73 antibody.

Experimental: Dose Expansion Sym021 (+Sym024)
Part III, dose expansion Sym024 and/or Sym021+Sym024
Drug: Sym021
Sym021 is a humanized anti-PD-1 antibody.
Other Name: Anti-PD-1

Drug: Sym024
Sym024 is an anti-CD73 antibody.




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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


Secondary Outcome Measures :
  1. 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

  2. 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)

  3. 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

  4. 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

  5. Maximum concentration (Cmax) [ Time Frame: 24 months ]
    Will be derived from observed data

  6. Time to reach maximum concentration (Tmax) [ Time Frame: 24 months ]
    Will be derived from observed data

  7. Trough concentration (Ctrough) [ Time Frame: 24 months ]
    Will be derived from observed data

  8. Terminal elimination half-life (T½) [ Time Frame: 24 months ]
    Will be estimated using non-compartmental methods and actual timepoints

  9. Clearance (CL) [ Time Frame: 24 months ]
    Will be estimated using non-compartmental methods and actual timepoints



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:

  • 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).

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): NCT04672434


Contacts
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Contact: U. Hansen +45 45265050 info@symphogen.com

Locations
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United States, Michigan
START Midwest Recruiting
Grand Rapids, Michigan, United States, 49545
Contact: Nehal Lakhani, MD PhD    616-954-5554    nehal.lakhani@startmidwest.com   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Jordi Rodon, MD PhD    713-792-5603    jrodon@mdanderson.org   
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78229
Contact: David Sommerhalder, MD    210-580-9500    dsommerhalder@nextoncology.com   
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 1Z5
Contact: Anna Spreafico, MD PhD    416-946-3308    anna.spreafico@uhn.ca   
Sponsors and Collaborators
Symphogen A/S
Investigators
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Principal Investigator: N. Lakhani, MD PhD START Midwest, USA
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Responsible Party: Symphogen A/S
ClinicalTrials.gov Identifier: NCT04672434    
Other Study ID Numbers: Sym024-01
First Posted: December 17, 2020    Key Record Dates
Last Update Posted: July 2, 2021
Last Verified: July 2021
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:
Metastatic solid tumor
Cholangiocarcinoma (CCA)
Locally advanced/unresectable
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)
Colorectal carcinoma (CRC)
Gastric carcinoma (GC)
Esophageal carcinoma (EsoCA)
Mesothelioma (Meso)
Sym021
Sym024
Head and neck squamous cell carcinoma (HNSCC)
Additional relevant MeSH terms:
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Neoplasms
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes