Biodesix, Inc.

Globeimmune, Inc.

University of Texas System

Heinrich Röder

Julia Grigorieva

Joanna Röder

Maxim Tsypin

Carlos Oliveira

Arni Steingrimsson

Krista Meyer

Senait Asmellash

Kevin Sayers

Caroline Maher

Devalingam Mahalingam

Jenna Allen

Thomas Campbell

Robert W Georgantas, Iii

Laura Maguire

Jeffrey Weber

Ami Steingrimsson

A method is disclosed of predicting cancer patient response to immune checkpoint inhibitors, e.g., an antibody drug blocking ligand activation of programmed cell death 1 (PD-1) or CTLA4. The method includes obtaining mass spectrometry data from a blood-based sample of the patient, obtaining integrated intensity values in the mass spectrometry data of a multitude of pre-determined mass-spectral features; and operating on the mass spectral data with a programmed computer implementing a classifier. The classifier compares the integrated intensity values with feature values of a training set of class-labeled mass spectral data obtained from a multitude of melanoma patients with a classification algorithm and generates a class label for the sample. A class label 'early' or the equivalent predicts the patient is likely to obtain relatively less benefit from the antibody drug and the class label “late” or the equivalent indicates the patient is likely to obtain relatively greater benefit from the antibody drug.

Predictive test for patient benefit from antibody drug blocking ligand activation of the T-cell programmed cell death 1 (PD-1) checkpoint protein and classifier development methods

Laboratory test apparatus for conducting a mass spectrometry test on a blood-based sample of a cancer patient includes a classification procedure implemented in a programmed computer that generates a class label. In one form of the test, 'Test 1', if the sample is labelled “Bad” or equivalent the patient is predicted to exhibit primary immune resistance if they are later treated with anti-PD-1 or anti-PD-L1 therapies. In “Test 2” the Bad class label predicts that the patient will have a poor prognosis in response to treatment by either anti-PD-1 or anti-PD-L1 therapies or alternative chemotherapies, such as docetaxel or pemetrexed. “Test 3” identifies patients that are likely to have a poor prognosis in response to treatment by either anti-PD-1 or anti-PD-L1 therapies but have improved outcomes on alternative chemotherapies. A Good class label by either Test 1 or 2 predicts very good outcome on anti-PD-1 or anti-PD-L1 monotherapy.

Apparatus and method for identification of primary immune resistance in cancer patients

A method for predicting an unfavorable outcome for a patient admitted to a hospital, e.g., with a COVID-19 infection is described. Attributes from an electronic health record for the patient are obtained including at least findings obtained at admission, basic patient characteristics, and laboratory data. The attributes are supplied to a classifier implemented in a programmed computer which is trained to predict a risk of the unfavorable outcome. The classifier is arranged as a hierarchical combination of (a) an initial binary classifier stratifying the patient into either a high risk group or a low risk group, and (b) child classifiers further classifying the patient in a lowest risk group or a highest risk group depending how the initial binary classifier stratified the patient as either a member of the high risk or low risk group. The initial binary classifier is configured as a combination of a trained classification decision tree and a logistical combination of atomic classifiers with drop-out regularization.

Method for predicting risk of unfavorable outcomes, e.g., in COVID-19 hospitalization, from clinical characteristics and basic laboratory findings

A method is disclosed for predicting in advance whether a melanoma patient is likely to benefit from high dose IL2 therapy in treatment of the cancer. The method makes use of mass spectrometry data obtained from a blood-based sample of the patient and a computer configured as a classifier and making use of a reference set of mass spectral data obtained from a development set of blood-based samples from other melanoma patients. A variety of classifiers for making this prediction are disclosed, including a classifier developed from a set of blood-based samples obtained from melanoma patients treated with high dose IL2 as well as melanoma patients treated with an anti-PD-1 immunotherapy drug. The classifiers developed from anti-PD-1 and IL2 patient sample cohorts can also be used in combination to guide treatment of a melanoma patient.

Predictive test for melanoma patient benefit from interleukin-2 (IL2) therapy

A method of generating a classifier includes a step of classifying each member of a development set of samples with a class label in a binary classification scheme with a first classifier; and generating a second classifier using a classifier development process with an input classifier development set being the members of the development set assigned one of the two class labels in the binary classification scheme by the first classifier. The second classifier stratifies the members of the set with an early label into two further sub-groups. We also describe identifying a plurality of different clinical sub-groups within the development set based on the clinical data and for each of the different clinical sub-groups, conducting a classifier generation process for each of the clinical sub-groups thereby generating clinical subgroup classifiers. We further describe an example of a hierarchical arrangement of such classifiers and their use in predicting, in advance of treatment, ovarian cancer patient outcomes on platinum-based chemotherapy.

Classifier generation methods and predictive test for ovarian cancer patient prognosis under platinum chemotherapy

A method of predicting whether an MDS patient has a good or poor prognosis uses a general purpose computer configured as a classifier and mass-spectrometry data obtained from a blood-based sample. The classifier assigns a classification label of either Early or Late (or the equivalent) to the patient's sample. Patients classified as Early are predicted to have a poor prognosis or worse survival whereas those patients classified as Late are predicted to have a relatively better prognosis and longer survival time. The groupings demonstrated a large effect size between groups in Kaplan-Meier analysis of survival. Most importantly, while the classifications generated were correlated with other prognostic factors, such as IPSS score and genetic category, multivariate and subgroup analysis showed that they had significant independent prognostic power complementary to the existing prognostic factors.

Predictive test for prognosis of myelodysplastic syndrome patients using mass spectrometry of blood-based sample

A blood-based sample from a cancer patient is subject to mass spectrometry and the resulting mass spectral data is classified with the aid of a computer to see if the patient is a member of a class of patients having a poor prognosis. If so, the mass spectral data is further classified with the aid of the computer by a second classifier which identifies whether the patient is nevertheless likely to obtain durable benefit from immunotherapy drugs, e.g., immune checkpoint inhibitors, anti-CTLA4 drugs, and high dose interleukin-2.

Method for identification of cancer patients with durable benefit from immunotherapy in overall poor prognosis subgroups

A method is disclosed of predicting cancer patient response to immune checkpoint inhibitors, e.g., an antibody drug blocking ligand activation of programmed cell death 1 (PD-1) or CTLA4. The method includes obtaining mass spectrometry data from a blood-based sample of the patient, obtaining integrated intensity values in the mass spectrometry data of a multitude of pre-determined mass-spectral features; and operating on the mass spectral data with a programmed computer implementing a classifier. The classifier compares the integrated intensity values with feature values of a training set of class-labeled mass spectral data obtained from a multitude of melanoma patients with a classification algorithm and generates a class label for the sample. A class label 'early' or the equivalent predicts the patient is likely to obtain relatively less benefit from the antibody drug and the class label 'late' or the equivalent indicates the patient is likely to obtain relatively greater benefit from the antibody drug.

Classifier generation methods are described in which features used in classification (e.g., mass spectral peaks) are selected, or deselected using bagged filtering. A development sample set is split into two subsets, one of which is used as a training set the other of which is set aside. We define a classifier (e.g., K-nearest neighbor, decision tree, margin-based classifier or other) using the training subset and at least one of the features (or subsets of two or more features in combination). We apply the classifier to a subset of samples. A filter is applied to the performance of the classifier on the sample subset and the at least one feature is added to a 'filtered feature list' if the classifier performance passes the filter. We do this for many different realizations of the separation of the development sample set into two subsets, and, for each realization, different features or sets of features in combination. After all the iterations are performed the filtered feature list is used to either select features, or deselect features, for a final classifier.

Bagged filtering method for selection and deselection of features for classification

A method and system for predicting in advance of treatment whether a cancer patient is likely, or not likely, to obtain benefit from administration of a yeast-based immune response generating therapy, which may be yeast-based immunotherapy for mutated Ras-based cancer, alone or in combination with another anti-cancer therapy. The method uses mass spectrometry of a blood-derived patient sample and a computer configured as a classifier using a training set of class-labeled spectra from other cancer patients that either benefited or did not benefit from an immune response generating therapy alone or in combination with another anti-cancer therapy. Also disclosed are methods of treatment of a cancer patient, comprising administering a yeast-based immune response generating therapy, which may be yeast-based immunotherapy for mutated Ras-based cancer, to a patient selected by a test in accordance with predictive mass spectral methods disclosed herein, in which the class label for the spectra indicates the patient is likely to benefit from the yeast-based immunotherapy.

Mass-spectral method for selection, and de-selection, of cancer patients for treatment with immune response generating therapies

A programmed computer functioning as a classifier operates on mass spectral data obtained from a blood-based patient sample to predict indolence or aggressiveness of prostate cancer. Methods of generating the classifier and conducting a test on a blood-based sample from a prostate cancer patient using the classifier are described.

Predictive test for aggressiveness or indolence of prostate cancer from mass spectrometry of blood-based sample

Hepatocellular carcinoma (HCC) is detected in a patient with liver disease. Mass spectrometry data from a blood-based sample from the patient is compared to a reference set of mass-spectrometry data from a multitude of other patients with liver disease, including patients with and without HCC, in a general purpose computer configured as a classifier. The classifier generates a class label, such as HCC or No HCC, for the test sample. A laboratory system for early detection of HCC in patients with liver disease is also disclosed. Alternative testing strategies using AFP measurement and a reference set for classification in the form of class-labeled mass spectral data from blood-based samples of lung cancer patients are also described, including multi-stage testing.

Early detection of hepatocellular carcinoma in high risk populations using MALDI-TOF mass spectrometry

Predictive test for melanoma patient benefit from antibody drug blocking ligand activation of the T-cell programmed cell death 1 (PD-1) checkpoint protein and classifier development methods

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Steamboat Springs, CO, United States of America

Heinrich Röder