A Study Evaluating TAS-102 Plus Nivolumab in Patients With MSS CRC

• ClinicalTrials.gov Identifier: NCT02860546
• Recruitment Status: Completed
• First Posted: August 9, 2016
• Last Update Posted: September 19, 2018
• Sponsor: Taiho Oncology, Inc.
• Information provided by (Responsible Party): Taiho Oncology, Inc.

Tracking Information

• First Submitted Date: July 13, 2016
• First Posted Date: August 9, 2016
• Last Update Posted Date: September 19, 2018
• Study Start Date: August 2016
• Actual Primary Completion Date: November 3, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 4, 2016)

Immune-related overall response rate (irORR) [ Time Frame: Up to 2 Years ]

Immune-related overall response rate (irORR) is defined as as the incidence of complete (irCR) and partial (irPR) responses in the efficacy population

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 4, 2016)

• Recommended Phase 2 dose for the combination therapy of TAS 102 and nivolumab [ Time Frame: 4 Months ]
  To confirm the recommended Phase 2 dose
• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: Up to 2 Years ]
  Safety and Tolerability is defined as AEs graded using NCI criteria for AEs (CTCAE)
• Overall Response Rate (ORR) [ Time Frame: Up to 2 Years ]
  To estimate the ORR using Response Evaluation Criteria in Solid Tumors (RECIST)
• Progression Free Survival (PFS) based on irRC [ Time Frame: Up to 2 Years ]
  PFS is defined as the time from the date of randomization until radiological disease based on immune-related response criteria (irRC) or death
• Progression Free Survival (PFS) based on RECIST [ Time Frame: Up to 2 Years ]
  PFS is defined as the time from the date of randomization until radiological disease based on RECIST or death
• Disease Control Rate (DCR) based on irRC [ Time Frame: Up to 2 Years ]
  DCR is defined as the proportion of patients with objective evidence of complete response, partial response and stable disease based on irRC
• Disease Control Rate (DCR) based on RECIST [ Time Frame: Up to 2 Years ]
  DCR is defined as the proportion of patients with objective evidence of complete response, partial response and stable disease based on RECIST
• Overall Survival (OS) [ Time Frame: Up to 2 Years ]
  To estimate the OS

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: August 4, 2016)

• MSI status by Polymerase Chain Reaction (PCR) with clinical and toxicity [ Time Frame: Up to 2 Years ]
  To explore the association of MSI status by polymerase chain reaction (PCR) with clinical response and toxicity
• PD L1 positivity by Immunohistochemistry (IHC) with clinical and toxicity [ Time Frame: Up to 2 Years ]
  To explore the association of programmed cell death ligand 1 (PD L1) positivity by Immunohistochemistry (IHC) with clinical response and toxicity
• Tumor infiltrating lymphocyte characteristics by Flow Cytometry with clinical and toxicity [ Time Frame: Up to 2 Years ]
  To explore the association of tumor infiltrating lymphocyte characteristics by Flow cytometry with clinical response and toxicity

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: A Study Evaluating TAS-102 Plus Nivolumab in Patients With MSS CRC
• Official Title: A Phase 2 Study With Safety Lead-in, Evaluating TAS-102 Plus Nivolumab in Patients With Microsatellite Stable Refractory Metastatic Colorectal Cancer
• Brief Summary: A Phase 2 Study with Safety Lead-in, Evaluating TAS-102 Plus Nivolumab in Patients with Microsatellite Stable Refractory Metastatic Colorectal Cancer

Detailed Description

This is a multicenter, single arm, safety lead-in, Phase 2 study, using Simon's 2 stage design evaluating the safety and efficacy of TAS-102 plus nivolumab in patients with Microsatellite-stable refractory metastatic colorectal cancer

Stage 1: Patients will be enrolled and after Cycle 1 treatment, they will be evaluated for the safety and tolerability of the combination therapy. Assuming a tolerated dose is confirmed additional patients evaluable for response will be enrolled and followed for a minimum of 6 months and there will be an interim analysis to assess the safety and efficacy to determine whether the second stage will open for enrollment.

Stage 2: Additional patients evaluable for response assessment will be enrolled and followed for a minimum of 6 months.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Refractory Metastatic Colorectal Cancer

Intervention

• Drug: TAS-102
  One Arm Only (of TAS 102 plus nivolumab)
  Other Name: Lonsurf®
• Drug: nivolumab
  One Arm Only (of TAS 102 plus nivolumab)
  Other Name: Opdivo®

Study Arms

Experimental: TAS-102 and Nivolumab

Interventions:

• Drug: TAS-102
• Drug: nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 4, 2016): 35
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: November 3, 2017
• Actual Primary Completion Date: November 3, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Has provided written informed consent.
2. Patient with confirmed histologically proven metastatic or locally advanced colorectal adenocarcinoma who are MSS (ie, not MSI) based on either an analysis of tissue from a prior biopsy or based on tissue from a new biopsy.
3. Patient with the presence of at least 1 lesion with measurable disease as defined by 10 mm in the longest diameter for a soft tissue lesions or 15 mm in the short axis for a lymph node by RECIST and irRC criteria for a response assessment.
4. Patient has received at least 2 prior lines of standard chemotherapies for mCRC and is refractory to or failing those chemotherapies.
5. Age ≥ 18 years.
6. Eastern Cooperative Oncology Group performance status of 0 to 1
7. Life expectancy of ≥ 4 months.
8. Has adequate organ function
9. Women of childbearing potential must have a negative pregnancy test (urine or serum) within 7 days before starting study drugs. Is able to take medications orally

Exclusion Criteria:

1. Has a serious illness or medical condition

2. Treatment with any of the following within the specified time frame before enrollment:

   1. Major surgery within the past 4 weeks (the surgical incision should be fully healed before study drug administration).
   2. Any anticancer therapy within the past 3 weeks before enrollment.
   3. Extended field radiation within the past 4 weeks or limited field radiation within the past 2 weeks before enrollment.
   4. Any investigational drug/device received within the past 4 weeks or 5 times the half-life (whichever is shorter) before enrollment.
3. Previous treatment with TAS-102.
4. Prior treatment with anti-PD-1, anti- PD-L1, anti programmed cell death ligand 2, anti-CD137, anti-OX-40, anti CD40, anti cytotoxic T lymphocyte associated antigen-4 antibodies, or any other immune checkpoint inhibitors.
5. Unresolved toxicity of ≥ Common Terminology Criteria for Adverse Events version (CTCAE) version 4.03 grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum induced neurotoxicity).
6. Prior events of immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune mediated nephritis and renal dysfunction, immune mediated rash, immune mediated encephalitis, and history of infusion reactions to nivolumab.
7. Known or assumed hypersensitivity to TAS-102 or nivolumab or any of its ingredients, including polysorbate 80-containing infusion.
8. Previous severe hypersensitivity reaction to treatment with another mAb.
9. Pregnant or lactating female.
10. Inappropriate for entry into this study in the judgment of the investigator.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02860546
• Other Study ID Numbers: TAS-102-203
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Study results using compiled efficacy and safety data will be published at congress or to a journal, without any identification of the patients.

• Responsible Party: Taiho Oncology, Inc.
• Study Sponsor: Taiho Oncology, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Taiho Oncology, Inc.
• Verification Date: September 2018