A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors
Verified August 2016 by Tesaro, Inc.
Information provided by (Responsible Party):
First received: March 9, 2016
Last updated: August 10, 2016
Last verified: August 2016
This is a multicenter, open-label, first-in-human Phase 1 study evaluating the anti programmed death receptor 1 (anti-PD-1) antibody TSR-042 in patients with advanced solid tumors who have limited available treatment options. The study will be conducted in 2 parts: dose escalation and cohort expansion.
Advanced or Metastatic Solid Tumors
||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors
Primary Outcome Measures:
- Safety and tolerability of TSR-042 using Common Terminology Criteria for Adverse Events (CTCAE v4.03) in patients with advanced solid tumors [ Time Frame: Part 1 Dose Escalation - Approximately 9 months ]
- Antitumor activity of TSR-042 in patients with advanced solid tumors, in terms of objective response rate (ORR) as assessed by the Investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Part 2 Expansion - Approximately 12 months ]
- Recommended Phase 2 dose (RP2D) and schedule [ Time Frame: Part 1 and Part 2 - Approximately 12 months ]
Secondary Outcome Measures:
- PD-1 receptor occupancy prior to and after the first dose of TSR-042 to measure changes in serum cytokines [ Time Frame: Part 1 - Approximately 12 months ]
- Overall Response Rate (ORR) as assessed by using RECIST v1.1 [ Time Frame: Part 1 - Approximately 12 months ]
- Safety and tolerability of TSR-042 using CTCAE v4.03 [ Time Frame: Part 2 - Approximately 12 months ]
- Immunogenicity of TSR-042 [ Time Frame: Part 1 and Part 2 - Approximately 12 months ]
- ORR by immune-related RECIST (irRECIST) [ Time Frame: Part 1 and Part 2 - Approximately 24 months ]
- Duration of Response (DOR) by RECIST v 1.1 [ Time Frame: Part 1 and Part 2 - Approximately 24 months ]
- Disease Control Rate (DCR) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 1 and Part 2 - Approximately 24 months ]
- Progression-free survival (PFS) by RECIST v 1.1 and by irRECIST [ Time Frame: Part 1 and Part 2 - Approximately 24 months ]
- Overall Survival (OS) [ Time Frame: Part 1 and Part 2 - Approximately 24 months ]
- Pharmacokinetic (PK) Parameter: Area Under the Concentration (AUC),0-last [ Time Frame: Approximately 12 months ]
- PK Parameter: AUC,0-infinity [ Time Frame: Approximately 12 months ]
- PK Parameter: AUC at steady state (AUC,ss) [ Time Frame: Approximately 12 months ]
- PK Parameter: Minimum Concentration (Cmin) [ Time Frame: Approximately 12 months ]
- PK Parameter: Maximum Concentration (Cmax) [ Time Frame: Approximately 12 months ]
- PK Parameter: Cmin,ss [ Time Frame: Approximately 12 months ]
- PK Parameter: Cmax,ss [ Time Frame: Approximately 12 months ]
- PK Parameter: Clearance (CL) [ Time Frame: Approximately 12 months ]
- PK Parameter: Volume of Distribution (Vz) [ Time Frame: Approximately 12 months ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||February 2019 (Final data collection date for primary outcome measure)
Experimental: Part 1 - Dose Escalation
Using a modified 3+3 design, Part 1 (dose escalation) will initially evaluate ascending weight-based dose levels of TSR-042 administered via intravenous (IV) infusion, once every two weeks.
Part 2 - Expansion Cohort - Part 2 of the study will further explore the safety and clinical activity of TSR-042 in patients with selected tumor types. Dosing in Part 2 will be initiated with the dose determined to be safe based on dose limiting toxicities (DLTs) in Part 1 with consideration of available Pharmacokinetic/Pharmacodynamic (PK/PD) data.
TSR-042 is a humanized monoclonal antibody that binds with high affinity to PD-1 resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2).
|Ages Eligible for Study:
||18 Years and older (Adult, Senior)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
- Patient has received prior therapy with an anti-programmed death receptor 1 (anti-PD-1), anti-PD-1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) agent.
- Known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are clinically stable off steroids for at least 7 days prior to study treatment. Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability.
- Known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell cancer (SqCC) of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
- Poor medical risk.
- Pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study.
- Immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
- Known active hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid (HCV RNA) (qualitative) is detected).
- Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- History of interstitial lung disease.
- Patient has not recovered (ie, to ≤ Grade 1 or to baseline) from radiation- and chemotherapy-induced adverse events (AEs) or received transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF) or recombinant erythropoietin) within 3 weeks prior to the first dose of study drug.
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study drug.
- Received prior anticancer therapy (chemotherapy, targeted therapies, radiotherapy, or immunotherapy) within 21 days, or less than 5 times the half-life of the most recent therapy prior to study Day 1, whichever is shorter. Note: palliative radiation therapy to a small field ≥ 1 week prior to Day 1 of study treatment may be allowed.
- Patient has not recovered adequately (≤ Grade 1) from AEs and/or complications from any major surgery prior to starting therapy.
- Patient has received a vaccine within 7 days of planned start of study therapy.
- Known hypersensitivity to TSR-042 components or excipients.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02715284
|Goodyear, Arizona, United States, 85338 |
|Contact: Lisa Blaydorn, RN 623-207-3183 WesternTrials@ctca-hope.com |
|Scottsdale, Arizona, United States, 85258 |
|Contact: Joyce Schaffer 480-323-1339 email@example.com |
|San Antonio, Texas, United States, 78229 |
|Contact: Isabel Jimenez, RN, MSN 210-593-5252 firstname.lastname@example.org |
||Ellie Im, MD
History of Changes
|Other Study ID Numbers:
|Study First Received:
||March 9, 2016
||August 10, 2016
|Individual Participant Data
|Plan to Share IPD:
Keywords provided by Tesaro, Inc.:
Metastatic solid tumors
Advanced solid tumors
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on March 28, 2017
Physiological Effects of Drugs