KEYTRUDA (Page 12 of 21)
14.7 Microsatellite Instability-High or Mismatch Repair Deficient Cancer
The efficacy of KEYTRUDA was investigated in patients with MSI-H or mismatch repair deficient (dMMR), solid tumors enrolled in one of five uncontrolled, open-label, multi-cohort, multi-center, single-arm trials. Patients with active autoimmune disease or a medical condition that required immunosuppression were ineligible across the five trials. Patients received either KEYTRUDA 200 mg every 3 weeks or KEYTRUDA 10 mg/kg every 2 weeks. Treatment continued until unacceptable toxicity or disease progression that was either symptomatic, rapidly progressive, required urgent intervention, or occurred with a decline in performance status. A maximum of 24 months of treatment with KEYTRUDA was administered. For the purpose of assessment of anti-tumor activity across these 5 trials, the major efficacy outcome measures were ORR as assessed by BICR according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and DoR.
|Study||Design and Patient Population||Number of Patients||MSI-H/dMMR Testing||Dosage||Prior Therapy|
|CRC = colorectal cancerPCR = polymerase chain reactionIHC = immunohistochemistry|
|KEYNOTE-016 NCT01876511|| ||28 CRC30 non-CRC||local PCR or IHC||10 mg/kg every 2 weeks|| |
|KEYNOTE-164 NCT02460198|| ||61||local PCR or IHC||200 mg every 3 weeks||Prior fluoropyrimidine, oxaliplatin, and irinotecan +/- anti-VEGF/EGFR mAb|
|KEYNOTE-012 NCT01848834|| ||6||central PCR||10 mg/kg every 2 weeks||≥1 prior regimen|
|KEYNOTE-028 NCT02054806|| ||5||central PCR||10 mg/kg every 2 weeks||≥1 prior regimen|
|KEYNOTE-158 NCT02628067|| ||19||local PCR or IHC (central PCR for patients in rare tumor non-CRC cohorts)||200 mg every 3 weeks||≥1 prior regimen|
A total of 149 patients with MSI-H or dMMR cancers were identified across the five trials. Among these 149 patients, the baseline characteristics were: median age of 55 years, 36% age 65 or older; 56% male; 77% White, 19% Asian, and 2% Black; and 36% ECOG PS of 0 and 64% ECOG PS of 1. Ninety-eight percent of patients had metastatic disease and 2% had locally advanced, unresectable disease. The median number of prior therapies for metastatic or unresectable disease was two. Eighty-four percent of patients with metastatic CRC and 53% of patients with other solid tumors received two or more prior lines of therapy.
The identification of MSI-H or dMMR tumor status for the majority of patients (135/149) was prospectively determined using local laboratory-developed, polymerase chain reaction (PCR) tests for MSI-H status or immunohistochemistry (IHC) tests for dMMR. Fourteen of the 149 patients were retrospectively identified as MSI-H by testing tumor samples from a total of 415 patients using a central laboratory developed PCR test. Forty-seven patients had dMMR cancer identified by IHC, 60 had MSI-H identified by PCR, and 42 were identified using both tests.
Efficacy results are summarized in Tables 67 and 68.
|NR = not reached|
|Objective Response Rate|
|ORR (95% CI)||39.6% (31.7, 47.9)|
|Complete response rate||7.4%|
|Partial response rate||32.2%|
|Duration of Response|
|Median in months (range)||NR (1.6+, 22.7+)|
|% with duration ≥6 months||78%|
|Objective Response Rate||Duration of Response range|
|N||n (%)||95% CI||(months)|
|CR = complete responsePR = partial responseSD = stable diseasePD = progressive diseaseNE = not evaluable|
|CRC||90||32 (36%)||(26%, 46%)||(1.6+, 22.7+)|
|Non-CRC||59||27 (46%)||(33%, 59%)||(1.9+, 22.1+)|
|Endometrial cancer||14||5 (36%)||(13%, 65%)||(4.2+, 17.3+)|
|Biliary cancer||11||3 (27%)||(6%, 61%)||(11.6+, 19.6+)|
|Gastric or GE junction cancer||9||5 (56%)||(21%, 86%)||(5.8+, 22.1+)|
|Pancreatic cancer||6||5 (83%)||(36%, 100%)||(2.6+, 9.2+)|
|Small intestinal cancer||8||3 (38%)||(9%, 76%)||(1.9+, 9.1+)|
|Breast cancer||2||PR, PR||(7.6, 15.9)|
|Prostate cancer||2||PR, SD||9.8+|
|Small cell lung cancer||1||CR||8.9+|
|Renal cell cancer||1||PD|
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.