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.
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
France2 sites
Centre Georges-François Leclerc, Department of Medical Oncology
Dijon, 21000
Institut de Cancerologie de L'Ouest
Saint-Herblain, 44805
Spain2 sites
Vall d'Hebron Institute of Oncology
Barcelona, 08035
Hospital Universitario San Carlos
Madrid, 28040
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).
- Conditions
- Metastatic Cancer, Solid Tumor
- 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.
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. 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.
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
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
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)
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
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
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
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
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
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
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
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
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
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
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
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
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.
- First posted24 Nov 2020
- Study start12 Oct 2020
- Primary completion3 Jun 2024
- Study completion3 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Symphogen A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nehal Lakhani, MD, Principal investigator, START Midwest
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
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04641871
- Acronym / sponsor ID
- Sym021-02
- Conditions
- Metastatic Cancer, Solid Tumor
- Keywords
- Locally advanced/unresectable, Metastatic solid tumor, Anti-PD-1, PD-1, PD1, Anti-TIM-3, TIM-3, TIM3
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Symphogen A/SIndustry (pharma, biotech, devices)
- Study start
- 12 Oct 2020 (actual)
- Primary completion
- 3 Jun 2024 (actual)
- Study completion
- 3 Jun 2024 (actual)
- First posted
- 24 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Sym021+Sym022 [ARM A] for BTC patients | Experimental | Drug: Sym021, Drug: Sym022Sym021 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. |
| Sym021+Sym023 [ARM B] for BTC patients | Experimental | Drug: Sym021, Drug: Sym023Sym021 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. |
| Sym021+Sym023+irrinotecan for BTC patients | Experimental | Drug: Sym021, Drug: Sym023, Drug: Irinotecan HydrochlorideSym021 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. |
| Sym021+Sym023+irrinotecan for ESCC patients | Experimental | Drug: Sym021, Drug: Sym023, Drug: Irinotecan HydrochlorideSym021 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
- 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.
- Patients with measurable disease according to RECIST v1.1
Key exclusion criteria (21 listed)
- Patients with central nervous system (CNS) malignancy, untreated or unstable metastases
- Patients with significant cardiovascular disease
- Patients with
- Patients with a significant pulmonary disease or condition
- Patients with a current or recent (within 6 months) significant gastrointestinal disease or condition
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sym021Also: Anti-PD-1IV infusion over 30 minutes on day 1 and 15 of each cycle. | Drug | 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 |
| Sym022Also: Anti-LAG-3IV infusion over 30 minutes on day 1 and 15 of each cycle. | Drug | Sym021+Sym022 [ARM A] for BTC patients |
| Sym023Also: Anti-TIM-3IV infusion over 30 minutes on day 1 and 15 of each cycle. | Drug | Sym021+Sym023 [ARM B] for BTC patients, Sym021+Sym023+irrinotecan for BTC patients, Sym021+Sym023+irrinotecan for ESCC patients |
| Irinotecan HydrochlorideIV 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 | Drug | Sym021+Sym023+irrinotecan for BTC patients, Sym021+Sym023+irrinotecan for ESCC patients |
Primary outcome
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
Objective Response Rate (ORR) per Investigator assessment of antitumor activity (based on radiological evidence per RECIST v1.1)
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)
Time frame: Through study completion up to 30 days after last dose of the three combinations
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
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)
Time frame: Through study completion up to a maximum of 24 months
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
13 secondary outcomes
Peak plasma (irinotecan) and serum( mAbs) Concentration (Cmax) of the 3 combinations (Sym021+Sym022 and Sym021+Sym023 and Sym021+Sym023+irinotecan)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: First dose of study drug and throughout the trial, up to 2 years
To confirm the RP2D of each combination
Time frame: 36 month
Evaluation of Duration of Response (DOR)
Time frame: Until disease progression or end of study, whichever comes first, assessed up to 24 months
Evaluation of Progression-Free Survival (PFS)
Time frame: From first study drug dose until disease progression or end of study, whichever comes first, assessed up to 24 months
Evaluation of Disease Control Rate (DCR), defined as CR, PR, or stable disease (SD) ≥6 months
Time frame: Until disease progression or end of study, whichever comes first, assessed up to 6 months
Evaluation of duration of response.
Time frame: Until disease progression or end of study, whichever comes first, assessed up to 24 months
Evaluation of Objective Response Rate (ORR) per Investigator assessment (based on Immunotherapeutics Response Evaluation Criteria in Solid Tumors [iRECIST])
Time frame: Until disease progression or end of study, whichever comes first, assessed up to 24 months
Evaluation Overall Survival (OS)
Time frame: From first dose of study drug until death or latest survival follow-up assessed up to 30 month
Evaluation of immunogenicity of each antibody drug in the combinations
Time frame: From screening up to 30 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nehal Lakhani, MD principal investigator
START Midwest
17 sites in 4 countries: see every site and its status.
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?
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.