Methods of treating cancer
Inventors
Frampton, Garrett Michael • Yelensky, Roman • Sun, James Xin • Johnson, Douglas Buckner • Lovly, Christine Marie • Sosman, Jeffrey Alan • Fabrizio, David • Stephens, Philip James • Miller, Vincent A.
Assignees
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Publication Number
US-11725247-B2
Publication Date
2023-08-15
Expiration Date
Abstract
Methods and compositions for treating cancer such as melanomas are disclosed.
Core Innovation
The disclosure identifies tumor mutational burden as a predictor of benefit from therapy comprising an inhibitor of PD-1 or PD-L1 in melanoma. It describes acquiring a responder-status value from the number of somatic alterations in a predetermined gene set in a melanoma sample or a sample derived from the melanoma. The alterations are detected using [procedural detail omitted for safety], and the resulting value is compared with a reference value.
Tumor mutational burden serves as a clinically practical surrogate for broader mutational load, where higher mutation counts track whole-exome metrics and correlate with response, progression-free survival, and overall survival. The disclosure describes response stratification using alteration-per-megabase thresholds and mutation surrogates. The responder-status value guides treatment, therapy selection, and responder classification. The background section is omitted, so the problem stated there is not explicitly described in patent.
Claims Coverage
The claims encompass four inventive features across independent claims 1, 14, 15, and 16, covering treatment, therapy selection, subject evaluation, and an evaluation system for melanoma response to PD-1 or PD-L1 inhibitor therapy.
Treatment guided by responder status
Claim 1 covers acquiring responder status for a subject with melanoma using tumor mutational burden, measured as the number of somatic alterations in a predetermined gene set, with detection by [procedural detail omitted for safety], and administering PD-1 or PD-L1 inhibitor therapy when responder status is increased compared with a reference value.
Selection of PD-1 or PD-L1 inhibitor therapy
Claim 14 covers selecting therapy for a subject with melanoma based on responder status comprising a tumor mutational burden measure from a melanoma sample or a sample derived from the melanoma, wherein an increased value compared with a reference indicates that the subject is or is likely to be a responder.
Evaluation of melanoma response
Claim 15 covers evaluating a subject with melanoma by acquiring responder status based on tumor mutational burden and identifying the subject as a responder, complete responder, partial responder, or non-responder based on whether the responder-status value is equal to or greater than, or less than, a reference value.
System for evaluating melanoma response
Claim 16 covers a processor and memory configured to acquire responder status based on tumor mutational burden and identify the subject as a responder, complete responder, partial responder, or non-responder by comparing the responder-status value with a reference value.
The four independent claims cover tumor mutational burden-based responder assessment for melanoma across treatment, therapy selection, evaluation, and system configurations, sharing common claim elements including a predetermined gene set, somatic alteration measurement, and comparison with a reference value.
Stated Advantages
The approach is described as faster, less costly, and more objective.
It is described as capable of detecting actionable alterations alongside tumor mutational burden.
Higher tumor mutational burden correlates with response to PD-1 or PD-L1 inhibitor therapy, providing an objective basis for evaluating response and selecting or guiding therapy.
High-mutation-burden tumors are reported to be associated with longer progression-free survival and overall survival.
Documented Applications
Guiding administration of PD-1 or PD-L1 inhibitor therapy for a subject with melanoma based on responder status.
Selecting PD-1 or PD-L1 inhibitor therapy for a subject with melanoma based on whether the tumor mutational burden-based responder-status value indicates likely response.
Evaluating and classifying a subject with melanoma as a responder, complete responder, partial responder, or non-responder to PD-1 or PD-L1 inhibitor therapy.
Response-guided adjustments to therapy dose or schedule, addition of an agent for a non-responder or partial responder, and prognostication of melanoma progression.
Using a system comprising a processor and memory to evaluate response to PD-1 or PD-L1 inhibitor therapy and inform treatment reports.
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