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

NCT ID: NCT04641871

Last Updated: 2024-06-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-12

Study Completion Date

2024-06-03

Brief Summary

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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

Detailed Description

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The study will evaluate safety and efficacy in patients with:

* Biliary tract carcinomas patients who have progressed on one prior line of gemcitabine and platinum-based chemotherapy in the metastatic setting.
* Esophageal squamous cell carcinoma patients who have progressed on one prior line of platinum-based chemotherapy in the metastatic setting.

The trial is set up as 3 sub-studies.

* Sub-study 1 includes biliary tract carcinoma patients and is composed of 2 investigational combination treatment arms (Sym021+Sym022 \[Arm A\] and Sym021+Sym023 \[Arm B\]).
* Sub-study 2, includes biliary tract carcinoma patients and is composed of one investigational combination treatment arm:Sym021+Sym023+irinotecan. A safety lead- in phase is included to assess tolerability of the combination. A Study Safety Team will review clinical and laboratory safety data and will make decisions regarding the continued enrollment after the safety lead-in phase.
* Sub-Study 3, includes esophageal squamous cell carcinoma patients and is composed of one investigational combination treatment arm: Sym021+Sym023+irinotecan. Dose of irinotecan in this arm will be selected based upon the safety lead in in sub-study 2 period.

August 2021 : Based upon results from a recent per protocol Interim Analysis (IA) it is has been decided as of 3rd of August 2021 to stop further enrollment into Sub-study 1 Arm A (Sym021+Sym022). Future patients will be allocated to either Sub-study 1 Arm B (Sym021+Sym023) or Sub-study 2 (Sym021+Sym023+irinotecan).

Conditions

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Metastatic Cancer Solid Tumor

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Sym021+Sym022 [ARM A] for BTC patients

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.

Group Type EXPERIMENTAL

Sym021

Intervention Type DRUG

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

Sym022

Intervention Type DRUG

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

Sym021+Sym023 [ARM B] for BTC patients

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.

Group Type EXPERIMENTAL

Sym021

Intervention Type DRUG

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

Sym023

Intervention Type DRUG

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

Sym021+Sym023+irrinotecan for BTC patients

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.

Group Type EXPERIMENTAL

Sym021

Intervention Type DRUG

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

Sym023

Intervention Type DRUG

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

Irinotecan Hydrochloride

Intervention Type 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 ESCC patients

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.

Group Type EXPERIMENTAL

Sym021

Intervention Type DRUG

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

Sym023

Intervention Type DRUG

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

Irinotecan Hydrochloride

Intervention Type 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

Interventions

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Sym021

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

Intervention Type DRUG

Sym022

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

Intervention Type DRUG

Sym023

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

Intervention Type DRUG

Irinotecan Hydrochloride

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

Intervention Type DRUG

Other Intervention Names

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Anti-PD-1 Anti-LAG-3 Anti-TIM-3

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* Patients with central nervous system (CNS) malignancy, untreated or unstable metastases
* 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 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.
* For Sub-study 3: Anti-TIM-3 containing regimen, or combination with any other systemic or localized therapy or any other IO therapies (other than anti-PD-(L)1 agents).
* Patients must not be on warfarin, if they have a history of acute immune-related thrombocytopenia; patients must not be on strong cytochrome P450 (CYP) 3A4 inducers, strong CYP3A4 inhibitors, or strong UGT1A1 inhibitors.
* 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
* Sub-study 1 and Sub-study 2: Patients with known FGFR2 fusion or rearrangement, or IDH1 mutation.
* For Sub-study 3: Patients with a history of significant toxicities associated with previous administration of immune checkpoint inhibitors that necessitated permanent discontinuation of that therapy.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Symphogen A/S

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nehal Lakhani, MD

Role: PRINCIPAL_INVESTIGATOR

START Midwest

Locations

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University of Colorado

Aurora, Colorado, United States

Site Status

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

University of Kansas Medical Center (KUMC)

Westwood, Kansas, United States

Site Status

START Midwest

Grand Rapids, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Mount Sinai - PRIME

New York, New York, United States

Site Status

Montefiore Medical Center PRIME

The Bronx, New York, United States

Site Status

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status

MD Anderson

Houston, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Centre Georges-François Leclerc, Department of Medical Oncology

Dijon, , France

Site Status

Institut de Cancerologie de L'Ouest

Saint-Herblain, , France

Site Status

Vall d'Hebron Institute of Oncology

Barcelona, , Spain

Site Status

Hospital Universitario San Carlos

Madrid, , Spain

Site Status

Countries

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United States Canada France Spain

Other Identifiers

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Sym021-02

Identifier Type: -

Identifier Source: org_study_id

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