1 / 10

About These Slides

Phase II KEYNOTE-170/KEYNOTE-013 Update: Pembrolizumab in Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma. Integrating New Malignant Hematology Findings Into Practice: Independent Conference Coverage of ASH 2018* December 1-4, 2018; San Diego, California.

tea
Download Presentation

About These Slides

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Phase II KEYNOTE-170/KEYNOTE-013 Update: Pembrolizumab in Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma Integrating New Malignant Hematology Findings Into Practice: Independent Conference Coverage of ASH 2018* December 1-4, 2018; San Diego, California *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. Supported by educational grants from AbbVie, AstraZeneca, Celgene Corporation, Dova Pharmaceuticals, Incyte, Jazz Pharmaceuticals, Novartis Pharmaceuticals, Pharmacyclics, Seattle Genetics, and Takeda Oncology.

  2. About These Slides • Please feel free to use, update, and share some or all of these slides in your noncommercial presentations to colleagues or patients • When using our slides, please retain the source attribution: • These slides may not be published, posted online, or used in commercial presentations without permission. Please contact permissions@clinicaloptions.com for details Slide credit: clinicaloptions.com

  3. KEYNOTE-170/KEYNOTE-013 Pembrolizumab in R/R PMBCL: Background • R/R PMBCL associated with poor outcomes, few treatment options[1] • Genetic abnormalities (eg, activation of NF-kB, JAK/STAT[2]; amplification/translocation of 9p24[3-6]) often lead to overexpression of PD-L1 and PD-L2 in PMBCL • May be sensitive to PD-1 blockade • Pembrolizumab: humanized IgG4 monoclonal antibody against PD-1 • Phase Ib KEYNOTE-013 showed preliminary efficacy, safety of pembrolizumab in PMBCL[1] • 41% ORR; 12% CR rate; median DoR not reached • Phase II KEYNOTE-170 extends KEYNOTE-013 and adds biomarker analyses[1] • Current analysis presents updated safety, efficacy data from KEYNOTE-013 and full KEYNOTE-170 cohort with pembrolizumab in patients with R/R PMBCL Slide credit: clinicaloptions.com 1. Armand. ASH 2018. Abstr 228. 2. Savage. Blood. 2003;12:3871. 3. Green. Blood. 2010;17:3266. 4. Twa. Blood. 2014;123:2062. 5. Shi. Am J Surg Path. 2014;38:1715. 6. Chen. Clin Can Res. 2013;13:3462.

  4. Primary endpoints: ORR, safety (KEYNOTE-013 only) Secondary endpoints: DoR, PFS, OS, safety (KEYNOTE-170) KEYNOTE-170/KEYNOTE-013 Pembrolizumab in R/R PMBCL: Study Design Phase Ib KEYNOTE-013 Pembrolizumab 10 mg/kg Q2W (patients 1-10) or 200 mg Q3W (patients 11-21) R/R PMBCL patients ≥ 18 yrs of age without ASCT* (N = 21) Treatment up to 2 yrs or until unacceptable toxicity, PD, or study withdrawal Response assessment by PET/CT scan: • KEYNOTE-013: Wk 12 then Q8W (10 mg/kg Q2W) or Wks 6, 12 then Q9W (200 mg Q3W), IWG 2007 criteria • KEYNOTE-170: Wk 12 then Q12W, IWG 2007 criteria Slide credit: clinicaloptions.com Phase II KEYNOTE-170 R/R PMBCL patients ≥ 18 yrs of age without ASCT,* failed ≥ 2 prior regimens (N = 53) Pembrolizumab 200 mg Q3W Treatment up to 2 yrs or until unacceptable toxicity, PD, or study withdrawal *Failed, ineligible, or refused. Armand. ASH 2018. Abstr 228. NCT02576990.

  5. KEYNOTE-170/KEYNOTE-013 Pembrolizumab in R/R PMBCL: Patient Characteristics Slide credit: clinicaloptions.com Armand. ASH 2018. Abstr 228.

  6. KEYNOTE-170/KEYNOTE-013 Pembrolizumab in R/R PMBCL: Efficacy Slide credit: clinicaloptions.com *Insufficient data for response assessment.†Cheson criteria.‡Lugano criteria. §2 patients converted from PR to CR after 12 mos; 4 patients maintained CR after 2 yrs on treatment (2.3+, 2.5+, 3+, 3.5+ yrs). ǁNo relapses in patients with CR reported at database lock. Armand. ASH 2018. Abstr 228.

  7. KEYNOTE-170/KEYNOTE-013 Pembrolizumab in R/R PMBCL: Safety *Discontinuation. †Myositis. ‡Pneumonitis. §Includes thyroid disease, colitis, myositis, pneumonitis. Slide credit: clinicaloptions.com Armand. ASH 2018. Abstr 228.

  8. KEYNOTE-170/KEYNOTE-013 Pembrolizumab in R/R PMBCL: Biomarker Analyses • PD-L1 H score significantly associated with PFS (P = .029) • Median PFS for 0, mos: 2.0 (0.1-9.5) • Median PFS for 1-99, mos: 6.3 (2.6-11.1) • Patients with tissue available for biomarker analysis (n = 42) • KEYNOTE-013 (n = 5), KEYNOTE-170 (n = 37) • IHC membranous staining evaluated and scored by 2 independent pathologists • H score by IHC reflects percentage of PD-L1+ cells and relative intensity of staining • Range 0-300: 0 = no/low PD-L1+; 100 = ~ 50% cells PD-L1+ • PD-L1 H score correlated with magnitude of 9p24 abnormality by FISH (n = 40; P = .038) Slide credit: clinicaloptions.com *Both H scores = 0, at least 1 H score ≥ 100, all others 1-99. †P = .016. ‡P < .001. Armand. ASH 2018. Abstr 228.

  9. KEYNOTE-170/KEYNOTE-013 Pembrolizumab in R/R PMBCL: Conclusions • Pembrolizumab results in durable responses in R/R PMBCL • Median DoR not yet reached with median follow-up of 29.1 mos (KEYNOTE-013), 12.5 mos (KEYNOTE-170) • 12-mo OS > 50%; durable CR in both studies • Manageable toxicity profile • Biomarker analyses: PD-L1 H score associated with PFS; patients lacking expression of PD-L1/L2 have reduced response to pembrolizumab, worse outcomes • Data support receptor-level blockade in R/R PMBCL, per investigators • Future studies needed to validate/refine • Pembrolizumab received accelerated FDA approval for R/R PMBCL in June 2018 Slide credit: clinicaloptions.com Armand. ASH 2018. Abstr 228.

  10. Go Online for More CCO Coverage of ASH 2018! clinicaloptions.com/oncology Short slideset summaries and additional CME-certified analyses with expert facultycommentary on key studies in: Leukemias Lymphomas/CLL Multiple Myeloma Other Hematologic Diseases

More Related