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

Phase 1

Completed

• Conditions: Solid Tumor; Metastatic Cancer
• Interventions: Drug: Sym024; Drug: Sym021

• Registration Number: NCT04672434
• Lead Sponsor: 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.

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 2a of this study will assess the safety and tolerability of Sym024 when first administered as a single agent during Cycle 1 (safety lead-in) followed by administration in combination with Sym021 during Cycle 2 and subsequent cycles.

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.

April 2024: The above was the study design at trial start. Per protocol, implementation of a part 3 would require an amendment. However, this was never done as it was decided not to include a part 3.

Study Timeline

• Study Start: 2020-11-19
• Study First Submitted: 2020-12-07
• Study First Submitted QC: 2020-12-16
• Study First Posted: 2020-12-17
• Primary Completion: 2024-11-22
• Study Completion: 2024-11-22
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-04
• Last Update Posted: 2024-12-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

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)
  9. Cervical carcinoma (CC) (includes adeno, squamous and mixed adeno-squamous carcinoma histology subtypes)

• 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.

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Sym024 Dose Level 2	Sym024	Part I, Sym024 monotherapy dose level 2
Sym024 Dose Level 3	Sym024	Part I, Sym024 monotherapy dose level 3
Sym024 Dose Level 4	Sym024	Part I, Sym024 monotherapy dose level 4
Sym024 Dose Level -1	Sym024	Part I, Sym024 monotherapy dose level -1. Evaluate only if needed based on tolerability
Sym021+Sym024 Dose Level 2	Sym021	Part II, Sym021 in combination with dose level 2 of Sym024
Sym021+Sym024 Dose Level 2	Sym024	Part II, Sym021 in combination with dose level 2 of Sym024
Sym024 Dose Level 1	Sym024	Part I, Sym024 monotherapy dose level 1
Sym021+Sym024 Dose Level 3	Sym021	Part II, Sym021 in combination with dose level 3 of Sym024
Sym021+Sym024 Dose Level 3	Sym024	Part II, Sym021 in combination with dose level 3 of Sym024
Sym021+Sym024 Dose Level 4	Sym021	Part II, Sym021 in combination with dose level 4 of Sym024
Sym021+Sym024 Dose Level 4	Sym024	Part II, Sym021 in combination with dose level 4 of Sym024
Sym021+Sym024 Dose Level 5	Sym021	Part IIa, Sym024 monotherapy and in combination with Sym021
Sym021+Sym024 Dose Level 5	Sym024	Part IIa, Sym024 monotherapy and in combination with Sym021
Sym021+Sym024 Dose Level 1	Sym021	Part II, Sym021 in combination with dose level 1 of Sym024. Evaluate only if needed based on tolerability
Sym021+Sym024 Dose Level 1	Sym024	Part II, Sym021 in combination with dose level 1 of Sym024. Evaluate only if needed based on tolerability
Dose Expansion Sym021 (+Sym024)	Sym021	Part III, dose expansion Sym024 and/or Sym021+Sym024
Dose Expansion Sym021 (+Sym024)	Sym024	Part III, dose expansion Sym024 and/or Sym021+Sym024

Primary Outcome Measures

Name	Time	Method
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.	12 months	Assess the safety and tolerability of Sym024 and/or Sym021+Sym024 on a Q2W schedule. Assessment based on the occurrence of AEs
Part I: To evaluate the incidence, severity and relationship of (S)AEs to establish the MTD/MAD of Sym024 monotherapy.	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.	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

Secondary Outcome Measures

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

Trial Locations

Locations (4)

NEXT Oncology; 🇺🇸 San Antonio, Texas, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States