KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Clinical Trial Results
Advanced TMB-H Cancers
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Clinical Findings from KEYNOTE-158
Objective Response Rate and Duration of Response
Objective Response Rate (ORR): TMB ≥10 mut/Mb
Efficacy studied in 9 different cancers in 102 patientsResponse
Response
Duration of Response (DOR): TMB ≥10 mut/Mb
KEYTRUDA (n=30/102) |
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Median DORNot Reached(range: 2.2+ months to 34.8+ months)a |
Patients with responses lasting ≥12 months57% |
Patients with responses lasting ≥24 months50% |
Objective Response Rate (ORR): TMB ≥13 mut/Mb
Efficacy studied in 9 different cancers in 70 patientsResponse
Response
Duration of Response (DOR)
KEYTRUDA (n=26/70) |
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Median DORNot Reached(range: 2.2+ months to 34.8+ months)a |
Patients with responses lasting ≥12 months58% |
Patients with responses lasting ≥24 months50% |
Additional Information
Median follow-up time of 11.1 months.
In an exploratory analysis in 32 patients enrolled in KEYNOTE-158 whose cancer had TMB ≥10 mut/Mb and <13 mut/Mb, the ORR was 13% (95% CI, 4–29), including 2 complete responses and 2 partial responses.
Study Design from KEYNOTE-158
Study Overview
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Study Arms
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End Points
The major efficacy outcome measures were ORR and DOR in patients who received at least 1 dose of KEYTRUDA as assessed by blinded independent central review (BICR) according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Patient Population Details
Patients with previously treated unresectable or metastatic solid tumors identified as TMB-H (TMB ≥10 mut/Mb) in the following cancers:
- Anal
- Cervical
- Endometrial
- Mesothelioma
- Neuroendocrine
- Salivary
- Small cell lung
- Thyroid
- Vulvar