A Trial of Pembrolizumab (MK-3475) in Participants With Blood Cancers (MK-3475-013/KEYNOTE-013)
Summary
The purpose of this trial is to evaluate the safety, tolerability, and efficacy of pembrolizumab (MK-3475, KEYTRUDA®) and pembrolizumab in combination with lenalidomide (Cohort 5 only) in hematologic malignancies. The primary study hypotheses are that treatment with pembrolizumab will result in a clinically meaningful improvement in Objective Response Rate (ORR) or Complete Remission Rate (CRR). The study includes an initial dose determination to establish the recommended phase 2 dose (RP2D) of lenalidomide given in combination with pembrolizumab in Cohort 5. With Protocol Amendment 08, enrollment in the Multiple Myeloma arm (Cohort 2) has been completed and no further enrollment will be allowed and enrollment in the Non-Hodgkin Lymphoma Diffuse Large B Cell Lymphoma arm (Cohort 5) has been discontinued and no further enrollment will be allowed.
Timeline
- Start
- 2013-11-22
- Primary completion
- 2020-06-26
- Completion
- 2020-06-26
Outcome
Mixed primary results
registry NUMBER Cohort 1: Myelodysplastic Syndrome (MDS): 0.0 (0.0 to 10.5) Percentage of participants NCT01953692 ↗
registry analysis (superiority test); Cohort 1: Myelodysplastic Syndrome (MDS); p >0.9999; exact binomial distribution; note: one-sided p value NCT01953692 ↗
registry comparing the ORR for pembrolizumab to a fixed efficacy target of 10% using a binomial exact test. NCT01953692 ↗
registry NUMBER Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM): 0.0 (0.0 to 9.5) Percentage of participants NCT01953692 ↗
registry analysis (superiority test); Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM); p >0.9999; exact binomial distribution; note: one-sided p-value NCT01953692 ↗
registry comparing the ORR for pembrolizumab to a fixed efficacy target of 25% using a binomial exact test. NCT01953692 ↗
registry NUMBER Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL): 22.6 (11.1 to 38.3) Percentage of participants NCT01953692 ↗
registry analysis (superiority test); Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL); p = 0.0306; exact binomial distribution; note: one-sided p-value NCT01953692 ↗
registry comparing the complete remission for pembrolizumab to a fixed efficacy target of 10% using a binomial exact test. NCT01953692 ↗
registry NUMBER Pooled Cohort 4 Sub-cohorts (Cohorts 4A+4B+4C+4D): 22.1 (15.0 to 30.7) Percentage of participants NCT01953692 ↗
registry analysis (superiority test); Pooled Cohort 4 Sub-cohorts (Cohorts 4A+4B+4C+4D); p = 0.7696; exact binomial distribution; note: one-sided p-value NCT01953692 ↗
Publications
- Results Armand P, Shipp MA, Ribrag V, Michot JM, Zinzani PL, Kuruvilla J, Snyder ES, Ricart AD, Balakumaran A, Rose S, Moskowitz CH. Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. J Clin Oncol. 2016 Nov 1;34(31):3733-3739. doi: 10.1200/JCO.2016.67.3467.
- Results Ribrag V, Avigan DE, Green DJ, Wise-Draper T, Posada JG, Vij R, Zhu Y, Farooqui MZH, Marinello P, Siegel DS. Phase 1b trial of pembrolizumab monotherapy for relapsed/refractory multiple myeloma: KEYNOTE-013. Br J Haematol. 2019 Aug;186(3):e41-e44. doi: 10.1111/bjh.15888. Epub 2019 Apr 1. No abstract available.
- Kuruvilla J, Armand P, Hamadani M, Kline J, Moskowitz CH, Avigan D, Brody JD, Ribrag V, Herrera AF, Morschhauser F, Kanate A, Zinzani PL, Bitran J, Ghesquieres H, Schuster SJ, Farooqui M, Marinello P, Bartlett NL. Pembrolizumab for patients with non-Hodgkin lymphoma: phase 1b KEYNOTE-013 study. Leuk Lymphoma. 2023 Jan;64(1):130-139. doi: 10.1080/10428194.2022.2136956. Epub 2022 Nov 18.
- Garcia-Manero G, Ribrag V, Zhang Y, Farooqui M, Marinello P, Smith BD. Pembrolizumab for myelodysplastic syndromes after failure of hypomethylating agents in the phase 1b KEYNOTE-013 study. Leuk Lymphoma. 2022 Jul;63(7):1660-1668. doi: 10.1080/10428194.2022.2034155. Epub 2022 Mar 4.
- Griffin GK, Weirather JL, Roemer MGM, Lipschitz M, Kelley A, Chen PH, Gusenleitner D, Jeter E, Pak C, Gjini E, Chapuy B, Rosenthal MH, Xu J, Chen BJ, Sohani AR, Lovitch SB, Abramson JS, Ishizuka JJ, Kim AI, Jacobson CA, LaCasce AS, Fletcher CD, Neuberg D, Freeman GJ, Hodi FS, Wright K, Ligon AH, Jacobsen ED, Armand P, Shipp MA, Rodig SJ. Spatial signatures identify immune escape via PD-1 as a defining feature of T-cell/histiocyte-rich large B-cell lymphoma. Blood. 2021 Mar 11;137(10):1353-1364. doi: 10.1182/blood.2020006464.
- Armand P, Kuruvilla J, Michot JM, Ribrag V, Zinzani PL, Zhu Y, Marinello P, Nahar A, Moskowitz CH. KEYNOTE-013 4-year follow-up of pembrolizumab in classical Hodgkin lymphoma after brentuximab vedotin failure. Blood Adv. 2020 Jun 23;4(12):2617-2622. doi: 10.1182/bloodadvances.2019001367.
- Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G, Ozcan M, Portino S, Fogliatto L, Caballero MD, Walewski J, Gulbas Z, Ribrag V, Christian B, Perini GF, Salles G, Svoboda J, Zain J, Patel S, Chen PH, Ligon AH, Ouyang J, Neuberg D, Redd R, Chatterjee A, Balakumaran A, Orlowski R, Shipp M, Zinzani PL. Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 Dec 1;37(34):3291-3299. doi: 10.1200/JCO.19.01389. Epub 2019 Oct 14.
- van Vugt MJH, Stone JA, De Greef RHJMM, Snyder ES, Lipka L, Turner DC, Chain A, Lala M, Li M, Robey SH, Kondic AG, De Alwis D, Mayawala K, Jain L, Freshwater T. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019 Aug 8;7(1):212. doi: 10.1186/s40425-019-0663-4.
- Zinzani PL, Ribrag V, Moskowitz CH, Michot JM, Kuruvilla J, Balakumaran A, Zhang Y, Chlosta S, Shipp MA, Armand P. Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Blood. 2017 Jul 20;130(3):267-270. doi: 10.1182/blood-2016-12-758383. Epub 2017 May 10.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Lenalidomide | Other / unclassified | 20 mg | Oral |
| Subject | Lenalidomide | Other / unclassified | 25 mg | Oral |
| Subject | Pembrolizumab | Monoclonal antibody | 10 mg/kg | Intravenous |
| Subject | Pembrolizumab | Monoclonal antibody | 200 mg | Intravenous |