Methods and compositions for prediction of therapeutic efficacy of cancer treatments and cancer prognosis
Inventors
Sahin, Ugur • Tureci, Ozlem • Maurus, Daniel
Assignees
Ganymed Pharmaceuticals GmbH • TRON Translationale Onkologie an der Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz gGmbH • Astellas Pharma Inc
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Publication Number
US-12188097-B2
Publication Date
2025-01-07
Expiration Date
Abstract
The invention generally relates to methods and compositions for the prediction of therapeutic efficacy of cancer treatments and the prognosis of cancer. The invention discloses markers that are associated with favorable and unfavorable outcomes, respectively, in certain cancer treatments and are useful as prognostic markers for cancer. Methods involving these markers are disclosed for predicting cancer therapy benefit and prognosing clinical outcome for cancer patients.
Core Innovation
The invention concerns biomarker-driven methods for treating a human cancer patient having a CLDN18.2-positive tumor by predicting therapeutic efficacy and prognosis using patient SNP genotypes. The disclosed approach links specific FCGR3A single-nucleotide polymorphism genotypes with likely responder status and clinical outcomes such as progression-free survival and recurrence or stable disease-related outcomes.
A central aspect is determining or using a determined genotype for at least one SNP in a sample obtained from the cancer patient, wherein the at least one SNP includes FCGR3A rs396991. The disclosed selection criterion identifies the cancer patient as a likely responder to treatment with an anti-CLDN18.2 antibody based on the patient having a heterozygous FCGR3A rs396991 [TG] genotype or a homozygous FCGR3A rs396991 [TT] genotype, followed by administering the anti-CLDN18.2 antibody.
The patent further includes methods for detecting the state of FCGR3A rs396991 SNP in genomic DNA from a human patient having a CLDN18.2-positive cancer by contacting a detection reagent with a target nucleic acid and detecting hybridization between the detection reagent and the target nucleic acid. Additional SNP genotyping may be used by detecting nucleotide states at both alleles for at least one additional SNP, with the description including SNPs in genes such as MUC1, IL-10, DNMT3A, SMAD4, EGF, CDH1, and ERCC1.
Claims Coverage
The document includes three independent claims covering genotype-guided selection for anti-CLDN18.2 antibody therapy using FCGR3A rs396991, a treatment method limited to patients with specified FCGR3A rs396991 genotypes, and detection of the FCGR3A rs396991 SNP state in genomic DNA for identifying likely responders. Across these independent claims, the inventive subject matter centers on FCGR3A rs396991 genotype-based selection of likely responders and hybridization-based SNP detection in genomic DNA samples.
FCGR3A rs396991 genotype-based responder identification for anti-CLDN18.2 antibody treatment
Determining or having determined a genotype for at least one single-nucleotide polymorphism in a sample obtained from a human cancer patient having a CLDN18.2-positive tumor, the at least one SNP including FCGR3A rs396991; identifying the cancer patient as a likely responder to treatment with an anti-CLDN18.2 antibody based on the patient having a heterozygous FCGR3A rs396991 [TG] genotype or a homozygous FCGR3A rs396991 [TT] genotype; and administering the anti-CLDN18.2 antibody to the human cancer patient.
Anti-CLDN18.2 antibody administration to patients with specified FCGR3A rs396991 genotypes
Administering an anti-CLDN18.2 antibody to a human cancer patient, wherein the patient has been determined to have a heterozygous FCGR3A rs396991 [TG] genotype or a homozygous FCGR3A rs396991 [TT] genotype.
Hybridization-based detection of FCGR3A rs396991 genotype in genomic DNA and genotype-guided anti-CLDN18.2 treatment
Obtaining a sample comprising genomic DNA from a patient having a CLDN18.2-positive cancer; detecting which nucleotide is present at both alleles of FCGR3A rs396991 in the sample by contacting a detection reagent with a target FCGR3A rs396991-containing nucleic acid and detecting hybridization between the detection reagent and the target nucleic acid, wherein the state of the FCGR3A rs396991 SNP is homozygous [GG], homozygous [TT], or heterozygous [TG]; identifying the patient as a likely responder to treatment with an anti-CLDN18.2 antibody based on the patient having a heterozygous FCGR3A rs396991 [TG] genotype or a homozygous FCGR3A rs396991 [TT] genotype; and administering the anti-CLDN18.2 antibody to the patient.
Overall, the independent claims define genotype-guided treatment with an anti-CLDN18.2 antibody using FCGR3A rs396991 [TG] or [TT] to identify likely responders, with one independent claim also requiring hybridization-based detection of the FCGR3A rs396991 SNP state in genomic DNA before administering the antibody.
Stated Advantages
Identifies patients as likely responders to treatment with an anti-CLDN18.2 antibody based on FCGR3A rs396991 [TG] or [TT] genotype.
Supports predicting therapeutic efficacy and prognosis for CLDN18.2-positive cancer patients using patient SNP genotypes.
Documented Applications
Treating a human cancer patient having a CLDN18.2-positive tumor with an anti-CLDN18.2 antibody, selecting likely responders using FCGR3A rs396991 [TG] or [TT] genotypes (including gastroesophageal cancer embodiments in dependent claims).
Detecting the FCGR3A rs396991 SNP state in genomic DNA from a patient having a CLDN18.2-positive cancer using detection reagent contact and detecting hybridization, then using the result to identify a likely responder and administer the anti-CLDN18.2 antibody.
Clinical/biomarker study with IMAB362-treated gastric or gastroesophageal adenocarcinoma patients using SNP genotype profiling and linking specific SNP/Fc receptor/complement/SNP genotypes to responder/non-responder and progression-free survival.
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