Sym021 in Combination With Either Sym022 or Sym023 or Sym023 and Irinotecan in Patients With Recurrent Advanced Selected Solid Tumor Malignancies

NCT04641871 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: Sym021-02
• Study Type: interventional
• Target: 78
• Locations: 4 countries
• Sites: 17

Brief Summary

The study will evaluate the preliminary efficacy of 3 combinations (Sym021+Sym022, Sym021+Sym023 and Sym021+Sym023+irinotecan) in patients with biliary tract carcinomas (BTC) and with esophageal squamous cell carcinoma (ESCC) by assessing overall response rates (ORRs) per Investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 The study will also evaluate the safety and tolerability profile of the 3 combinations

Conditions

Metastatic Cancer; Solid Tumor

Keywords

Locally advanced/unresectable; Metastatic solid tumor; Anti-PD-1; PD-1; PD1; Anti-TIM-3; TIM-3; TIM3; Cholangiocarcinoma; CCA; Biliary Tract Carcinomas; Gallbladder; Esophageal Squamous Cell Carcinoma; ESCC; Irinotecan

Outcome Measures

Primary Outcomes (3)

• To evaluate the preliminary efficacy of the combinations Sym021+Sym022, Sym021+Sym023 and Sym021+Sym023+irinotecan in patients with BTC or ESCC by assessing overall response rates (ORRs) per Investigator assessment using RECISTv.1.1

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

  Until disease progression or end of study, whichever comes first, assessed up to 24 months

• 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 3 combinations (Sym021+Sym022, Sym021+Sym023 and Sym021+Sym023+irrinotecan)

  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

  Through study completion up to 30 days after last dose of the three combinations

• To evaluate the AEs leading to dose interruption, dose delays, and permanent treatment stop of the 3 combinations (Sym021+Sym022 and Sym021+Sym023 and Sym021+Sym023 +irinotecan)

  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

  Through study completion up to a maximum of 24 months

Secondary Outcomes (13)

• Peak plasma (irinotecan) and serum( mAbs) Concentration (Cmax) of the 3 combinations (Sym021+Sym022 and Sym021+Sym023 and Sym021+Sym023+irinotecan)

  First study dose and throughout the trial, up to 2 years

• Area under the serum concentration versus time curve (AUC) of the 3 combinations (Sym021+Sym022 and Sym021+Sym023 and Sym021+Sym023+ irinotecan)

  First dose of study drug and throughout the trial, up to 2 years

• Time to reach maximum concentration (Tmax) of the 3 combinations (Sym021+Sym022 and Sym021+Sym023 and Sym021+Sym023+irinotecan)

  First dose of study drug and throughout the trial, up to 2 years

• Trough concentration (Ctrough) of the 3 combinations (Sym021+Sym022 and Sym021+Sym023 and Sym021+Sym023 + irinotecan)

  First dose of study drug and throughout the trial, up to 2 years

• Plasma concentration for irinotecan and its metabolite in the combination Sym021+Sym023+ Irinotecan

  First dose of study drug and throughout the trial, up to 2 years

Study Arms (4)

Sym021+Sym022 [ARM A] for BTC patients

EXPERIMENTAL

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; Drug: Sym022

Sym021+Sym023 [ARM B] for BTC patients

EXPERIMENTAL

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; Drug: Sym023

Sym021+Sym023+irrinotecan for BTC patients

EXPERIMENTAL

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. After another 30-minute post-dosing interval, irinotecan will be infused over 90 minutes.

Drug: Sym021; Drug: Sym023; Drug: Irinotecan Hydrochloride

Sym021+Sym023+irrinotecan for ESCC patients

EXPERIMENTAL

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. After another 30-minute post-dosing interval, irinotecan will be infused over 90 minutes.

Drug: Sym021; Drug: Sym023; Drug: Irinotecan Hydrochloride

Interventions

Sym021 DRUG

IV infusion over 30 minutes on day 1 and 15 of each cycle.

Also known as: Anti-PD-1

Sym021+Sym022 [ARM A] for BTC patients; Sym021+Sym023 [ARM B] for BTC patients; Sym021+Sym023+irrinotecan for BTC patients; Sym021+Sym023+irrinotecan for ESCC patients

Sym022 DRUG

IV infusion over 30 minutes on day 1 and 15 of each cycle.

Also known as: Anti-LAG-3

Sym021+Sym022 [ARM A] for BTC patients

Sym023 DRUG

IV infusion over 30 minutes on day 1 and 15 of each cycle.

Also known as: Anti-TIM-3

Sym021+Sym023 [ARM B] for BTC patients; Sym021+Sym023+irrinotecan for BTC patients; Sym021+Sym023+irrinotecan for ESCC patients

Irinotecan Hydrochloride DRUG

IV infusion over 90 min on day 1 and 15 of the first 2 cycles. After 2 cycles of treatment, irinotecan may be discontinued at the Investigator's discretion

Sym021+Sym023+irrinotecan for BTC patients; Sym021+Sym023+irrinotecan for ESCC patients

Eligibility Criteria

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

You may qualify if:

• For Sub-study 1 and 2:
• Patients with locally advanced or metastatic biliary tract carcinoma including adenocarcinoma of the intra- and/or extra-hepatic bile ducts and gallbladder carcinoma. Patients with ampullary cancers are excluded.
• Patients must only have received and progressed on or be intolerant of first-line gemcitabine and platinum-based chemotherapy in metastatic/advanced setting and should not have received prior anti-PD-(L)1 therapy. Patients with known fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement, or isocitrate dehydrogenase 1 (IDH1) mutation will be excluded. Prior anti-PD-(L)1 therapy may be allowed during the trial if regulatory approval for such therapy is obtained while this trial is enrolling.
• For Sub-study 3:
• Patients with with locally advanced or metastatic esophageal squamous cell carcinoma
• Patients must only have received and progressed on or be intolerant of first-line platinum-based chemotherapy in metastatic/advanced setting and should have received prior anti-PD-(L)1 therapy. Patients with mixed adenosquamous histology cancers are excluded.
• For all Sub-studies :
• 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

You may not qualify if:

• Patients with central nervous system (CNS) malignancy, untreated or unstable metastases
• Patients with significant cardiovascular disease
• Patients with
• Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks prior to the first study drug dose
• 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 Gilbert's syndrome or patients with UGT1A1\*28 homozygosity (also known as UGT1A1 7/7 genotype)
• 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
• Patients with a history of organ transplantation
• Patients with human immunodeficiency virus (HIV) (HIV 1/2 antibodies) or active infection with hepatitis B virus or hepatitis C virus
• Prior therapy with irinotecan
• For Sub-study 1 and Sub-study 2: Anti-PD-(L)1, anti -LAG-3\* or anti-TIM-3 containing regimen, or combination with any other systemic or localized therapy or any other immuno-oncology (IO) therapies.

Sponsors & Collaborators

• Symphogen A/S: lead

Study Sites (17)

University of Colorado

Aurora, Colorado, 80045, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago

Chicago, Illinois, 60637-1470, United States

Location

University of Kansas Medical Center (KUMC)

Westwood, Kansas, 66205, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Mount Sinai - PRIME

New York, New York, 10029, United States

Location

Montefiore Medical Center PRIME

The Bronx, New York, 10461, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

MD Anderson

Houston, Texas, 77230, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1X5, Canada

Location

Centre Georges-François Leclerc, Department of Medical Oncology

Dijon, 21000, France

Location

Institut de Cancerologie de L'Ouest

Saint-Herblain, 44805, France

Location

Vall d'Hebron Institute of Oncology

Barcelona, 08035, Spain

Location

Hospital Universitario San Carlos

Madrid, 28040, Spain

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Cholangiocarcinoma; Esophageal Squamous Cell Carcinoma

Interventions

spartalizumab; Irinotecan

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma, Squamous Cell; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Nehal Lakhani, MD

  START Midwest

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 29, 2020
• First Posted: November 24, 2020
• Study Start: October 12, 2020
• Primary Completion: June 3, 2024
• Study Completion: June 3, 2024
• Last Updated: June 26, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); US (12); CA (1); FR (2)