NCT03311412

Brief Summary

The primary purpose of this study is to see if Sym021 is safe and tolerable as monotherapy, in combination with either Sym022 or Sym023, and in Combination with both Sym022 and Sym023 for patients with locally advanced/unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
89

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Nov 2017

Longer than P75 for phase_1

Geographic Reach
2 countries

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 3, 2017

Completed
14 days until next milestone

First Posted

Study publicly available on registry

October 17, 2017

Completed
1 month until next milestone

Study Start

First participant enrolled

November 20, 2017

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 23, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 23, 2022

Completed
Last Updated

May 30, 2023

Status Verified

May 1, 2023

Enrollment Period

4.3 years

First QC Date

October 3, 2017

Last Update Submit

May 25, 2023

Conditions

Metastatic CancerSolid TumorLymphoma

Keywords

Locally advanced/unresectableMetastatic solid tumorLymphomaAnti-PD-1PD-1PD1Anti-LAG-3LAG-3LAG3Anti-TIM-3TIM-3TIM3

Outcome Measures

Primary Outcomes (3)

  • Part 1: Assessment of treatment emergent adverse events (AEs) meeting DLT criteria.

    Assess the safety and tolerability of Sym021 monotherapy on a Q2W schedule. Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1.

    12 months

  • Part 2: Assessment of treatment emergent adverse events (AEs) meeting DLT criteria.

    Assess the safety and tolerability of the Sym021 RP2D in combination with sequential escalating doses of Sym022 or Sym023 on a Q2W schedule. Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1.

    12 months

  • Part 3: Assessment of treatment emergent adverse events (AEs) meeting DLT criteria.

    Assess the safety and tolerability of the Sym021 RP2D in combination with sequential escalating doses of Sym022 and Sym023 on a Q2W schedule. Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1.

    12 months

Secondary Outcomes (9)

  • Evaluation of the immunogenicity of Sym021 as a single agent and in combination with Sym022 and Sym023.

    24 months

  • Evaluation of objective response (OR) or stable disease (SD).

    24 months

  • Time to progression (TTP) of disease.

    24 months

  • Area under the concentration-time curve in a dosing interval (AUC)

    24 months

  • Maximum concentration (Cmax)

    24 months

  • +4 more secondary outcomes

Study Arms (17)

Sym021 Dose Level 1

EXPERIMENTAL

Part 1, Sym021 monotherapy dose level 1

Drug: Sym021

Sym021 Dose Level 2

EXPERIMENTAL

Part 1, Sym021 monotherapy dose level 2

Drug: Sym021

Sym021 Dose Level 3

EXPERIMENTAL

Part 1, Sym021 monotherapy dose level 3

Drug: Sym021

Arm A: Sym021+Sym022 Dose Level 1

EXPERIMENTAL

Part 2, Arm A: Sym021 RP2D in combination with dose level 1 of Sym022

Drug: Sym021Drug: Sym022

Arm A: Sym021+Sym022 Dose Level 2

EXPERIMENTAL

Part 2, Arm A: Sym021 RP2D in combination with dose level 2 of Sym022

Drug: Sym021Drug: Sym022

Arm A: Sym021+Sym022 Dose Level 3

EXPERIMENTAL

Part 2, Arm A: Sym021 RP2D in combination with dose level 3 of Sym022

Drug: Sym021Drug: Sym022

Arm A: Sym021+Sym022 Dose Level 4

EXPERIMENTAL

Part 2, Arm A: Sym021 RP2D in combination with dose level 4 of Sym022

Drug: Sym021Drug: Sym022

Arm B: Sym021+Sym023 Dose Level 1

EXPERIMENTAL

Part 2, Arm B: Sym021 RP2D in combination with dose level 1 of Sym023

Drug: Sym021Drug: Sym023

Arm B: Sym021+Sym023 Dose Level 2

EXPERIMENTAL

Part 2, Arm B: Sym021 RP2D in combination with dose level 2 of Sym023

Drug: Sym021Drug: Sym023

Arm B: Sym021+Sym023 Dose Level 3

EXPERIMENTAL

Part 2, Arm B: Sym021 RP2D in combination with dose level 3 of Sym023

Drug: Sym021Drug: Sym023

Arm B: Sym021+Sym023 Dose Level 4

EXPERIMENTAL

Part 2, Arm B: Sym021 RP2D in combination with dose level 4 of Sym023

Drug: Sym021Drug: Sym023

Arm B: Sym021+Sym023 Dose Level 5

EXPERIMENTAL

Part 2, Arm B: Sym021 RP2D in combination with dose level 5 of Sym023

Drug: Sym021Drug: Sym023

Sym021+Sym022+Sym023 Dose Level 1

EXPERIMENTAL

Part 3, Sym021 in combination with Sym022 and Sym023

Drug: Sym021Drug: Sym022Drug: Sym023

Sym021+Sym022+Sym023 Dose Level 2

EXPERIMENTAL

Part 3, Sym021 in combination with Sym022 and Sym023

Drug: Sym021Drug: Sym022Drug: Sym023

Sym021+Sym022+Sym023 Dose Level 3

EXPERIMENTAL

Part 3, Sym021 in combination with Sym022 and Sym023

Drug: Sym021Drug: Sym022Drug: Sym023

Sym021+Sym022+Sym023 Dose Level 4

EXPERIMENTAL

Part 3, Sym021 in combination with Sym022 and Sym023

Drug: Sym021Drug: Sym022Drug: Sym023

Sym021+Sym022+Sym023 Dose Level 5

EXPERIMENTAL

Part 3, Sym021 in combination with Sym022 and Sym023

Drug: Sym021Drug: Sym022Drug: Sym023

Interventions

Sym021DRUG

Sym021 is a humanized antibody that binds PD-1 with sub-nanomolar affinity and blocks binding of the inhibitory ligands PD-L1 and PD-L2, thus releasing PD-1-mediated inhibition of the immune response.

Also known as: Anti-PD-1
Arm A: Sym021+Sym022 Dose Level 1Arm A: Sym021+Sym022 Dose Level 2Arm A: Sym021+Sym022 Dose Level 3Arm A: Sym021+Sym022 Dose Level 4Arm B: Sym021+Sym023 Dose Level 1Arm B: Sym021+Sym023 Dose Level 2Arm B: Sym021+Sym023 Dose Level 3Arm B: Sym021+Sym023 Dose Level 4Arm B: Sym021+Sym023 Dose Level 5Sym021 Dose Level 1Sym021 Dose Level 2Sym021 Dose Level 3Sym021+Sym022+Sym023 Dose Level 1Sym021+Sym022+Sym023 Dose Level 2Sym021+Sym022+Sym023 Dose Level 3Sym021+Sym022+Sym023 Dose Level 4Sym021+Sym022+Sym023 Dose Level 5
Sym022DRUG

Sym022 is a recombinant, fully human antibody that binds LAG-3 and blocks the LAG-3/major histocompatibility complex class II (MHC-II) interaction, thus allowing for increased T-cell proliferation and cytokine production.

Also known as: Anti-LAG-3
Arm A: Sym021+Sym022 Dose Level 1Arm A: Sym021+Sym022 Dose Level 2Arm A: Sym021+Sym022 Dose Level 3Arm A: Sym021+Sym022 Dose Level 4Sym021+Sym022+Sym023 Dose Level 1Sym021+Sym022+Sym023 Dose Level 2Sym021+Sym022+Sym023 Dose Level 3Sym021+Sym022+Sym023 Dose Level 4Sym021+Sym022+Sym023 Dose Level 5
Sym023DRUG

Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.

Also known as: Anti-TIM-3
Arm B: Sym021+Sym023 Dose Level 1Arm B: Sym021+Sym023 Dose Level 2Arm B: Sym021+Sym023 Dose Level 3Arm B: Sym021+Sym023 Dose Level 4Arm B: Sym021+Sym023 Dose Level 5Sym021+Sym022+Sym023 Dose Level 1Sym021+Sym022+Sym023 Dose Level 2Sym021+Sym022+Sym023 Dose Level 3Sym021+Sym022+Sym023 Dose Level 4Sym021+Sym022+Sym023 Dose Level 5

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female patients, ≥ 18 years of age at the time of obtaining informed consent.
  • Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphoma.
  • Malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
  • Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
  • Measurable or non-measurable disease according to RECIST v1.1 or RECIL 2017.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
  • Persons of childbearing potential agreeing to use a highly effective method of contraception during the study beginning within 2 weeks prior to the first dose and continuing until 6 months after the last dose of study drug(s); men agreeing to refrain from sperm donation during this period.

You may not qualify if:

  • Women who are pregnant or intending to become pregnant before, during, or within 6 months after the last dose of study drug; women who are breastfeeding; persons of childbearing potential and not willing to use a highly effective method of contraception.
  • Central nervous system (CNS) malignancies; patients with known, untreated CNS or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
  • Hematologic malignancies other than lymphoma.
  • Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 4 weeks prior to Cycle 1/Day 1 (C1/D1) unless adequately treated and considered stable.
  • Active uncontrolled bleeding or a known bleeding diathesis.
  • Clinically significant cardiovascular disease or condition.
  • Significant ocular disease or condition, including history of an autoimmune or inflammatory disorder.
  • Significant pulmonary disease or condition.
  • Current or recent (within 6 months) significant gastrointestinal (GI) disease or condition.
  • An active, known, or suspected autoimmune disease, or a documented history of autoimmune disease or syndrome, requiring systemic steroids or other immunosuppressive medications.
  • History of organ transplantation (e.g., stem cell or solid organ transplant).
  • History of significant toxicities associated with previous administration of immune checkpoint inhibitors that necessitated permanent discontinuation of that therapy.
  • Patients with unresolved \> Grade 1 toxicity associated with any prior antineoplastic therapy except for persistent Grade 2 alopecia, peripheral neuropathy, decreased hemoglobin, lymphopenia, hypomagnesemia, and/or end-organ failure being adequately managed by hormone replacement therapy.
  • Inadequate recovery from any prior surgical procedure, or having undergone any major surgical procedure within 4 weeks prior to C1/D1.
  • Known history of human immunodeficiency virus (HIV) or known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

South Texas Accelerated Research Therapeutics (START) Midwest

Grand Rapids, Michigan, 49503, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78240, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Neoplasm MetastasisLymphoma

Interventions

spartalizumab

Condition Hierarchy (Ancestors)

Neoplastic ProcessesNeoplasmsPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms by Histologic TypeLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Lillian Siu, MD, FRCPC

    Princess Margaret Cancer Centre

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 3, 2017

First Posted

October 17, 2017

Study Start

November 20, 2017

Primary Completion

March 23, 2022

Study Completion

March 23, 2022

Last Updated

May 30, 2023

Record last verified: 2023-05

Data Sharing

IPD Sharing
Will not share

Locations

CA(1)US(3)