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Metastatic CancerPhase 1NCT04641871

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

A Phase 1 study testing Sym021, Sym022 and Sym023 in people with Metastatic Cancer and Solid Tumor, run by Symphogen A/S at 17 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Cancer, Solid Tumor
What is being tested?
Sym021, Sym022 and Sym023
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
17 sitesin 4 countries
Study dates
12 Oct 2020to 3 Jun 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

17 sites in 4 countries.

17 sites in 4 countries

United States12 sites

  • University of Colorado

    Aurora, Colorado, 80045

  • University of Chicago

    Chicago, Illinois, 60637-1470

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45267

  • Virginia Cancer Specialists, PC

    Fairfax, Virginia, 22031

  • START Midwest

    Grand Rapids, Michigan, 49546

  • MD Anderson

    Houston, Texas, 77230

  • Mayo Clinic - Jacksonville

    Jacksonville, Florida, 32224

  • Mount Sinai - PRIME

    New York, New York, 10029

  • Mayo Clinic

    Rochester, Minnesota, 55902

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Montefiore Medical Center PRIME

    The Bronx, New York, 10461

  • University of Kansas Medical Center (KUMC)

    Westwood, Kansas, 66205

Other trials in United States

France2 sites

  • Centre Georges-François Leclerc, Department of Medical Oncology

    Dijon, 21000

  • Institut de Cancerologie de L'Ouest

    Saint-Herblain, 44805

Other trials in France

Spain2 sites

  • Vall d'Hebron Institute of Oncology

    Barcelona, 08035

  • Hospital Universitario San Carlos

    Madrid, 28040

Other trials in Spain

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 1X5

Other trials in Canada

About this study

Official title: An Exploratory, Open-label, Multicenter Phase 1b Trial to Evaluate Safety and Efficacy of Sym021 (Anti-PD 1) in Combination With Either Sym022 (Anti-LAG-3) or Sym023 (Anti-TIM-3) or Sym023 and Irinotecan in Patients With Recurrent Advanced Selected Solid Tumor Malignancies

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

Read the detailed description

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).

Being tested
Sym021, Sym022, Sym023, Irinotecan Hydrochloride
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
Medical subject headings
Neoplasm Metastasis, Cholangiocarcinoma, Esophageal Squamous Cell Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sym021Drug

    Also called Anti-PD-1

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

  • Sym022Drug

    Also called Anti-LAG-3

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

  • Sym023Drug

    Also called Anti-TIM-3

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

  • Irinotecan HydrochlorideDrug

    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

Study groups in NCT04641871
Study groupRoleWhat they receive
Sym021+Sym022 [ARM A] for BTC patientsExperimentalSym021 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.
Receives: Drug: Sym021; Drug: Sym022
Sym021+Sym023 [ARM B] for BTC patientsExperimentalSym021 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.
Receives: Drug: Sym021; Drug: Sym023
Sym021+Sym023+irrinotecan for BTC patientsExperimentalSym021 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.
Receives: Drug: Sym021; Drug: Sym023; Drug: Irinotecan Hydrochloride
Sym021+Sym023+irrinotecan for ESCC patientsExperimentalSym021 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.
Receives: Drug: Sym021; Drug: Sym023; Drug: Irinotecan Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

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

  2. 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

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

  3. 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

    Measured: Through study completion up to a maximum of 24 months

Secondary outcomes (13)

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

    Peak serum concentration (Cmax) for each mAbs in each combination.

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

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

    Area under the serum concentration versus time curve (AUC) for each mAbs in each combination.

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

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

    Time to reach maximum concentration (Tmax) for each mAbs in each combination.

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

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

    Trough concentration (Ctrough) for each mAbs in each combination.

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

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

    Plasma concentration at the end of infusion for irinotecan and its metabolite in the combination Sym021+Sym023+ Irinotecan

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

  6. To confirm the RP2D of each combination

    Confirmation of the RP2D, based on the dose-response relationship (in case more than one dose level is implemented), overall tolerability and safety profile, and the PK and pharmacodynamic data

    Measured: 36 month

  7. Evaluation of Duration of Response (DOR)

    Duration of the OR will be determined from the day initial response is observed to day of progression is observed. Number and percentages of patients with documented OR will be presented.

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

  8. Evaluation of Progression-Free Survival (PFS)

    Will be calculated as from the first study drug dose to the day progression of disease is confirmed radiological or date of death.

    Measured: From first study drug dose until disease progression or end of study, whichever comes first, assessed up to 24 months

  9. Evaluation of Disease Control Rate (DCR), defined as CR, PR, or stable disease (SD) ≥6 months

    Will be calculated according to standard response criteria

    Measured: Until disease progression or end of study, whichever comes first, assessed up to 6 months

  10. Evaluation of duration of response.

    Will be calculated from the day the initial response is observed to the day progression of disease is observed

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

  11. Evaluation of Objective Response Rate (ORR) per Investigator assessment (based on Immunotherapeutics Response Evaluation Criteria in Solid Tumors [iRECIST])

    Will be based on Investigators assessment on Immunotherapeutic Response Evaluation Criteria in Solid Tumors (iRECIST)

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

  12. Evaluation Overall Survival (OS)

    Overall survival will be derived from start of treatment until death or latest survival follow-up.

    Measured: From first dose of study drug until death or latest survival follow-up assessed up to 30 month

  13. Evaluation of immunogenicity of each antibody drug in the combinations

    Occurrence of antidrug antibody (ADA) measured in serum at selected time points during the study

    Measured: From screening up to 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Nov 2020
  2. Study start12 Oct 2020
  3. Primary completion3 Jun 2024
  4. Study completion3 Jun 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04641871
Sponsor's protocol ID
Sym021-02
Status last verified
Jun 2024
First submitted
29 Oct 2020
Last updated
26 Jun 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Sym021, Sym022 and Sym023 in people with Metastatic Cancer and Solid Tumor, run by Symphogen A/S at 17 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, France, Spain, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Until disease progression or end of study, whichever comes first, assessed up to 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04641871.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2024.

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