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

NCT02860546 | Completed Phase 2 Results FDA Drug

• 1 other identifier: TAS-102-203
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

A Phase 2 Study with Safety Lead-in, Evaluating TAS-102 Plus Nivolumab in Participants with Microsatellite Stable Refractory Metastatic Colorectal Cancer

Conditions

Refractory Metastatic Colorectal Cancer

Keywords

Refractory; Metastatic; Colorectal cancer; TAS-102; Nivolumab; Microsatellite Stable; Programmed cell death protein1 (PD 1)

Outcome Measures

Primary Outcomes (1)

• Immune-Related Overall Response Rate (irORR)

  irORR was defined as the percentage of participants achieving a complete response (irCR) or partial response (irPR) based on irRC criteria. Per irRC criteria, Complete Response (irCR) was defined as the disappearance of all tumor lesions (measurable or not, and no new lesions)., Partial Response (irPR) was defined as a decrease in the sum of the products of the two largest perpendicular diameters (SPD) by 50 percent (%) or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) was defined as the failure to meet criteria for irCR or irPR in absence of progressive disease (irPD), irPD was defined as at least 25% increase in SPD relative to nadir.

  From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)

Secondary Outcomes (10)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  Cycle 1 (each cycle is of 4 weeks)

• Recommended Phase 2 Dose (RP2D)

  Cycle 1 (each cycle is of 4 weeks)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)

• Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities

  From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)

• Overall Response Rate (ORR)

  From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)

Study Arms (1)

TAS-102 + Nivolumab

EXPERIMENTAL

Participants received a dose of 35 milligrams per meter square (mg/m\^2) of TAS-102 tablets orally twice per day (BID) within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 milligrams per kilogram per dose (mg/kg/dose) Nivolumab intravenous (I.V) infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).

Drug: TAS-102; Drug: nivolumab

Interventions

TAS-102 DRUG

One Arm Only (of TAS 102 plus nivolumab)

Also known as: Lonsurf®

TAS-102 + Nivolumab

nivolumab DRUG

One Arm Only (of TAS 102 plus nivolumab)

Also known as: Opdivo®

TAS-102 + Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has provided written informed consent.
• Participants with confirmed histologically proven metastatic or locally advanced colorectal adenocarcinoma who are microsatellite stable (MSS) (ie, not microsatellite instable \[MSI\]) based on either an analysis of tissue from a prior biopsy or based on tissue from a new biopsy.
• Participants with the presence of at least 1 lesion with measurable disease as defined by 10 millimeters (mm) in the longest diameter for a soft tissue lesions or 15 mm in the short axis for a lymph node by response evaluation criteria in solid tumors (RECIST) and immune related response-criteria (irRC) for a response assessment.
• Participants has received at least 2 prior lines of standard chemotherapies for metastatic colorectal cancer (mCRC) and is refractory to or failing those chemotherapies.
• Age greater than or equal to (\>=) 18 years.
• Eastern Cooperative Oncology Group performance status of 0 to 1
• Life expectancy of \>=4 months.
• Has adequate organ function.
• 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.
• Is able to take medications "orally".

You may not qualify if:

• Has a serious illness or medical condition.
• Treatment with any of the following within the specified time frame before enrollment:
• Major surgery within the past 4 weeks (the surgical incision should be fully healed before study drug administration).
• Any anticancer therapy within the past 3 weeks before enrollment.
• Extended field radiation within the past 4 weeks or limited field radiation within the past 2 weeks before enrollment.
• Any investigational drug/device received within the past 4 weeks or 5 times the half-life (whichever is shorter) before enrollment.
• Previous treatment with TAS-102.
• Prior treatment with anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death ligand (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.
• 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).
• 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.
• Known or assumed hypersensitivity to TAS-102 or nivolumab or any of its ingredients, including polysorbate 80-containing infusion.
• Previous severe hypersensitivity reaction to treatment with another mAb.
• Pregnant or lactating female.
• Inappropriate for entry into this study in the judgment of the investigator.

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (3)

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Related Publications (1)

• Patel MR, Falchook GS, Hamada K, Makris L, Bendell JC. A phase 2 trial of trifluridine/tipiracil plus nivolumab in patients with heavily pretreated microsatellite-stable metastatic colorectal cancer. Cancer Med. 2021 Feb;10(4):1183-1190. doi: 10.1002/cam4.3630. Epub 2021 Feb 5.

  PMID: 33544407 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

trifluridine tipiracil drug combination; Nivolumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

After interim analysis, per study design plan, the trial was stopped for futility before enrollment into Stage 2.

Results Point of Contact

• Title: Taiho
• Organization: Taiho Oncology, Inc.

medicalinformation@taihooncology.com

844-878-2446

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2016
• First Posted: August 9, 2016
• Study Start: August 29, 2016
• Primary Completion: August 1, 2017
• Study Completion: September 7, 2017
• Last Updated: September 3, 2024
• Results First Posted: July 26, 2021

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share

Locations

US (3)