Description:
This study will evaluate the preliminary efficacy of the 2 combinations (Sym021+Sym022 and
Sym021+Sym023) in each tumor type under study by assessing ORRs per Investigator assessment
using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. This study will also
evaluate the safety and tolerability profile of the 2 combinations (Sym021+Sym022 and
Sym021+Sym023)
Title
- Brief Title: Sym021 in Combination With Either Sym022 or Sym023 in Patients With Advanced Solid Tumor Malignancies
- 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) in Patients With Advanced Solid Tumor Malignancies
Clinical Trial IDs
- ORG STUDY ID:
Sym021-02
- NCT ID:
NCT04641871
Conditions
- Metastatic Cancer
- Solid Tumor
Interventions
Drug | Synonyms | Arms |
---|
Sym021 | Anti-PD-1 | Sym021+Sym022 [ARM A] |
Sym022 | Anti-LAG-3 | Sym021+Sym022 [ARM A] |
Sym023 | Anti-TIM-3 | Sym021+Sym023 [ARM B] |
Purpose
This study will evaluate the preliminary efficacy of the 2 combinations (Sym021+Sym022 and
Sym021+Sym023) in each tumor type under study by assessing ORRs per Investigator assessment
using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. This study will also
evaluate the safety and tolerability profile of the 2 combinations (Sym021+Sym022 and
Sym021+Sym023)
Detailed Description
The study will evaluate safety and efficacy in participant with small cell lung cancer,
urothelial cancer and bladder cancer who have developed resistance to prior anti-PD1 or
anti-PD-L1 therapy and in patient with cholangiocarcinoma who have received at least 1 line
of standard of care therapy and have progressed on it
Trial Arms
Name | Type | Description | Interventions |
---|
Sym021+Sym022 [ARM A] | 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. | |
Sym021+Sym023 [ARM B] | 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. | |
Eligibility Criteria
Inclusion Criteria:
Patients must meet all the following criteria to be eligible for participation in the
study:
- Male or female patients, ≥18 years.
- Patients with documented (histologically or cytologically proven) unresectable,
locally advanced, or metastatic malignancies:
1. Urothelial cancer (UC)
2. Small cell lung cancer (SCLC)
3. Endometrial cancer (EC) of any histological subtype
4. Cholangiocarcinoma (CCA): unresectable or metastatic adenocarcinoma of the intra-
and/or extra-hepatic bile ducts
- Patients with UC, SCLC, and EC must have received prior anti-PD-(L)1 therapy with a
best response of CR/PR or durable SD
- 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:
- Has central nervous system (CNS) malignancies
- 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 a significant ocular disease or condition
- Patients with an active, known or suspected autoimmune disease
- Patients with any other serious/active/uncontrolled infection
- Prior therapy with anti-LAG-3 or anti-TIM-3 or combinations of these 2 antibodies with
anti-PD-(L)1 antibody or with any other systemic or localized therapy
- Patients with a history of significant toxicities associated with previous
administration of immune checkpoint inhibitors that necessitated permanent
discontinuation of that therapy
- 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | To evaluate the preliminary efficacy of the 2 combinations (Sym021+Sym022 and Sym021+Sym023) in each tumor type under study by assessing ORRs per Investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 |
Time Frame: | Until disease progression or end of study, whichever comes first, assessed up to 24 months |
Safety Issue: | |
Description: | Objective Response Rate (ORR) per Investigator assessment of antitumor activity (based on radiological evidence per RECIST v1.1) |
Secondary Outcome Measures
Measure: | Peak Plasma Concentration (Cmax) of the 2 combinations (Sym021+Sym022 and Sym021+Sym023) |
Time Frame: | First dose of study drug |
Safety Issue: | |
Description: | Peak Plasma Concentration (Cmax) for first dose of each drug in each combination. Will be derived from observed data |
Measure: | To confirm the RP2D of each combination |
Time Frame: | 36 month |
Safety Issue: | |
Description: | 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 |
Measure: | Evaluation of duration of response. |
Time Frame: | Until disease progression or end of study, whichever comes first, assessed up to 24 months |
Safety Issue: | |
Description: | Will be calculated from the day the initial response is observed to the day progression of disease is observed |
Measure: | To evaluate the immunogenicity of each drug in the combinations |
Time Frame: | From screening up to 30 month |
Safety Issue: | |
Description: | Occurrence of ADA measured in serum at selected timepoints during the study |
Measure: | Area under the plasma concentration versus time curve (AUC) of the 2 combinations (Sym021+Sym022 and Sym021+Sym023) |
Time Frame: | First study drug dose |
Safety Issue: | |
Description: | Area under the plasma concentration versus time curve (AUC) for first dose of each drug in each combination. Will be estimated using non-compartmental methods and actual time points |
Measure: | Time to reach maximum concentration (Tmax) of the 2 combinations (Sym021+Sym022 and Sym021+Sym023) |
Time Frame: | First study drug dose |
Safety Issue: | |
Description: | Time to reach maximum concentration (Tmax) for first dose of each drug in each combination. Will be derived from observed data. |
Measure: | Trough concentration (Ctrough) of the 2 combinations (Sym021+Sym022 and Sym021+Sym023) |
Time Frame: | First dose of study drug |
Safety Issue: | |
Description: | Trough concentration (Ctrough) for first dose of each drug in each combination. Will be derived from observed data. |
Measure: | Evaluation of Progression-Free Survival (PFS) (the PFS rate at 6 months will additionally be evaluated in patients with SCLC) |
Time Frame: | From first study drug dose until disease progression or end of study, whichever comes first, assessed up to 24 months |
Safety Issue: | |
Description: | Will be calculated as from the first study drug dose to the day progression of disease is confirmed radiological or date of death. |
Measure: | 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 |
Safety Issue: | |
Description: | Will be calculated according to standard response criteria |
Measure: | 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 |
Safety Issue: | |
Description: | Will be based on Investigators assessment on Immunotherapeutic Response Evaluation Criteria in Solid Tumors (iRECIST) |
Measure: | Evaluation Overall Survival (OS) |
Time Frame: | From first dose of study drug until death or latest survival follow-up assessed up to 30 month |
Safety Issue: | |
Description: | Overall survival will be derived from start of treatment until death or latest survival follow-up. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Symphogen A/S |
Trial Keywords
- Locally advanced/unresectable
- Metastatic solid tumor
- Anti-PD-1
- PD-1
- PD1
- Anti-LAG-3
- LAG-3
- LAG3
- Anti-TIM-3
- TIM-3
- TIM3
- Urothelial cancer
- UC
- Small Cell Lung Cancer
- SCLC
- Endometrial cancer
- EC
- Cholangiocarcinoma
- CCA
Last Updated
November 24, 2020