KEYNOTE-177: Phase 3, open-label, randomized study of first-line pembrolizumab (Pembro) versus investigator-choice chemotherapy for mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal carcinoma (mCRC)
| Autor: | Takayuki Yoshino, Minori Koshiji Rosales, Dung T. Le, Luis A. Diaz, Thierry André, Dirk Jäger, Johanna C. Bendell, Bao Lam, S. Peter Kang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Colorectal cancer Lymphocyte medicine.medical_treatment First line Pembrolizumab law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law Internal medicine Medicine Chemotherapy business.industry Microsatellite instability medicine.disease 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis DNA mismatch repair business |
| Zdroj: | Journal of Clinical Oncology. 36:TPS877-TPS877 |
| ISSN: | 1527-7755 0732-183X 0256-3002 |
| DOI: | 10.1200/jco.2018.36.4_suppl.tps877 |
| Popis: | TPS877 Background: Approximately 5% of mCRCs are dMMR, leading to high levels of MSI. CRCs with MSI-H have abundant lymphocyte infiltrates and strong expression of immune checkpoints. In the phase 2 KEYNOTE-016 study, the anti–programmed death 1 (PD-1) antibody pembro provided an ORR of 40% in patients (pts) with progressive dMMR mCRC vs 0% in pts with MMR-proficient mCRC. KEYNOTE-177 (ClinicalTrials.gov, NCT02563002) is an international, randomized, open-label, phase 3 study to evaluate the efficacy and safety of pembro vs standard-of-care (SOC) chemotherapy as first-line therapy for dMMR or MSI-H mCRC. Methods: Pts aged ≥18 years with locally confirmed dMMR or MSI-H stage IV CRC, measurable disease per RECIST v1.1 by local site assessment, ECOG performance status 0-1, adequate organ function, no active autoimmune disease or brain metastases, and no prior systemic therapy for mCRC are eligible. Pts will be randomized 1:1 to receive pembro 200 mg every 3 weeks (Q3W) or investigator’s choice of SOC chemotherapy (options include mFOLFOX6 or FOLFIRI alone or in combination with bevacizumab or cetuximab; must be chosen prior to randomization). Treatment will continue until disease progression, unacceptable toxicity, pt/investigator decision to withdrawal, or completion of 35 cycles (pembro only). Response will be evaluated Q9W per RECIST v1.1 by central imaging vendor review and per immune-related RECIST. Pts in the SOC arm who have disease progression and meet crossover criteria may be eligible to receive pembro for up to 17 treatment cycles. Eligible pts may continue pembro after initial RECIST-defined progression. AEs will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. Pts are to be followed up for survival Q9W. Primary end point is PFS per RECIST v1.1 by central imaging vendor review. Secondary end points include ORR per RECIST v1.1 by central imaging vendor review, OS, and safety and tolerability. Other end points include DOR and HRQoL. Planned enrollment in KEYNOTE-177 is 270 pts across 23 countries. Clinical trial information: NCT02563002. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|