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

NCT04672434 | Completed Phase 1 FDA Drug

• 1 other identifier: Sym024-01
• Study Type: interventional
• Target: 48
• Locations: 2 countries
• Sites: 4

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.

Conditions

Metastatic Cancer; Solid Tumor

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); Cervical carcinoma (CC)

Outcome Measures

Primary Outcomes (3)

• Part I: To evaluate the incidence, severity and relationship of (S)AEs to establish the MTD/MAD of Sym024 monotherapy.

  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

  28 days

• Part II: To evaluate the incidence, severity and relationship of (S)AEs to establish MTD/MAD of Sym024 in combination with Sym021.

  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

  28 days

• 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.

  Assess the safety and tolerability of Sym024 and/or Sym021+Sym024 on a Q2W schedule. Assessment based on the occurrence of AEs

  12 months

Secondary Outcomes (9)

• Evaluation of the immunogenicity of Sym024 as a single agent and in combination with Sym024

  24 months

• Evaluation of objective response (OR) or stable disease (SD)

  24 months

• Time to progression (TTP) of disease

  24 months

• Area under the concentration-time curve in a dosing interval (AUC)

  24 months

• Maximum concentration (Cmax)

  24 months

Study Arms (11)

Sym024 Dose Level 1

EXPERIMENTAL

Part I, Sym024 monotherapy dose level 1

Drug: Sym024

Sym024 Dose Level 2

EXPERIMENTAL

Part I, Sym024 monotherapy dose level 2

Drug: Sym024

Sym024 Dose Level 3

EXPERIMENTAL

Part I, Sym024 monotherapy dose level 3

Drug: Sym024

Sym024 Dose Level 4

EXPERIMENTAL

Part I, Sym024 monotherapy dose level 4

Drug: Sym024

Sym024 Dose Level -1

EXPERIMENTAL

Part I, Sym024 monotherapy dose level -1. Evaluate only if needed based on tolerability

Drug: Sym024

Sym021+Sym024 Dose Level 2

EXPERIMENTAL

Part II, Sym021 in combination with dose level 2 of Sym024

Drug: Sym021; Drug: Sym024

Sym021+Sym024 Dose Level 3

EXPERIMENTAL

Part II, Sym021 in combination with dose level 3 of Sym024

Drug: Sym021; Drug: Sym024

Sym021+Sym024 Dose Level 4

EXPERIMENTAL

Part II, Sym021 in combination with dose level 4 of Sym024

Drug: Sym021; Drug: Sym024

Sym021+Sym024 Dose Level 5

EXPERIMENTAL

Part IIa, Sym024 monotherapy and in combination with Sym021

Drug: Sym021; Drug: Sym024

Sym021+Sym024 Dose Level 1

EXPERIMENTAL

Part II, Sym021 in combination with dose level 1 of Sym024. Evaluate only if needed based on tolerability

Drug: Sym021; Drug: Sym024

Dose Expansion Sym021 (+Sym024)

EXPERIMENTAL

Part III, dose expansion Sym024 and/or Sym021+Sym024

Drug: Sym021; Drug: Sym024

Interventions

Sym021 DRUG

Sym021 is a humanized anti-PD-1 antibody.

Also known as: Anti-PD-1

Dose Expansion Sym021 (+Sym024); Sym021+Sym024 Dose Level 1; Sym021+Sym024 Dose Level 2; Sym021+Sym024 Dose Level 3; Sym021+Sym024 Dose Level 4; Sym021+Sym024 Dose Level 5

Sym024 DRUG

Sym024 is an anti-CD73 antibody.

Dose Expansion Sym021 (+Sym024); Sym021+Sym024 Dose Level 1; Sym021+Sym024 Dose Level 2; Sym021+Sym024 Dose Level 3; Sym021+Sym024 Dose Level 4; Sym021+Sym024 Dose Level 5; Sym024 Dose Level -1; Sym024 Dose Level 1; Sym024 Dose Level 2; Sym024 Dose Level 3; Sym024 Dose Level 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, ≥18 years.
• Documented (histologically or cytologically proven), locally advanced or metastatic solid tumor malignancy (must be one of the following):
• Squamous cell carcinoma of the head and neck
• Non-small-cell lung carcinoma-adenocarcinoma histology subtype
• Pancreatic ductal adenocarcinoma
• Cholangiocarcinoma
• Colorectal carcinoma (microsatellite stable \[MSS\] and microsatellite instability-high \[MSI-H\] phenotypes)
• Gastric carcinoma (includes gastroesophageal carcinoma)
• Esophageal carcinoma (includes squamous cell and adenocarcinoma)
• Mesothelioma (pleural and peritoneal)
• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Symphogen A/S: lead

Study Sites (4)

START Midwest

Grand Rapids, Michigan, 49545, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z5, Canada

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Squamous Cell Carcinoma of Head and Neck; Cholangiocarcinoma; Colorectal Neoplasms; Stomach Neoplasms; Esophageal Neoplasms; Mesothelioma; Uterine Cervical Neoplasms

Interventions

spartalizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms by Site; Adenocarcinoma; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Esophageal Diseases; Adenoma; Neoplasms, Mesothelial; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• N. Lakhani, MD PhD

  START Midwest, USA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2020
• First Posted: December 17, 2020
• Study Start: November 19, 2020
• Primary Completion: November 22, 2024
• Study Completion: November 22, 2024
• Last Updated: December 9, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (3)