Clinical Validation of Companion Diagnostics for the Selection of Patients with Non–Small Cell Lung Cancer Tumors Harboring Epidermal Growth Factor Receptor Exon 20 Insertion Mutations for Treatment with Amivantamab

Amivantamab, an epidermal growth factor receptor (EGFR)–c-Met bispecific antibody, targets activating/resistance EGFR mutations and MET mutations/amplifications. In the ongoing CHRYSALIS study (ClinicalTrials.gov Identifier: NCT02609776), amivantamab demonstrated antitumor activity in patients with non–small cell lung cancer harboring EGFR exon 20 insertion mutations (ex20ins) that progressed on or after platinum-based chemotherapy, a population in which amivantamab use has been approved by the US Food and Drug Administration. This bridging study clinically validated two novel candidate companion diagnostics (CDx) for use in detecting EGFR ex20ins in plasma and tumor tissue, Guardant360 CDx and Oncomine Dx Target Test (ODxT), respectively. From the 81 patients in the CHRYSALIS efficacy population, 78 plasma and 51 tissue samples were tested. Guardant360 CDx identified 62 positive (16 negative), and ODxT identified 39 positive (3 negative), samples with EGFR ex20ins. Baseline demographic and clinical characteristics were similar between the CHRYSALIS-, Guardant360 CDx–, and ODxT–identified populations. Agreement with local PCR/next-generation sequencing tests used for enrollment into CHRYSALIS demonstrated high adjusted negative (99.6% and 99.9%) and positive (100% for both) predictive values with the Guardant360 CDx and ODxT tests, respectively. Overall response rates were comparable between the CHRYSALIS, Guardant360 CDx, and ODxT populations. Both the plasma- and tissue-based diagnostic tests provided accurate, comprehensive, and complementary approaches to identifying patients with EGFR ex20ins who could benefit from amivantamab therapy. Amivantamab, an epidermal growth factor receptor (EGFR)–c-Met bispecific antibody, targets activating/resistance EGFR mutations and MET mutations/amplifications. In the ongoing CHRYSALIS study (ClinicalTrials.gov Identifier: NCT02609776), amivantamab demonstrated antitumor activity in patients with non–small cell lung cancer harboring EGFR exon 20 insertion mutations (ex20ins) that progressed on or after platinum-based chemotherapy, a population in which amivantamab use has been approved by the US Food and Drug Administration. This bridging study clinically validated two novel candidate companion diagnostics (CDx) for use in detecting EGFR ex20ins in plasma and tumor tissue, Guardant360 CDx and Oncomine Dx Target Test (ODxT), respectively. From the 81 patients in the CHRYSALIS efficacy population, 78 plasma and 51 tissue samples were tested. Guardant360 CDx identified 62 positive (16 negative), and ODxT identified 39 positive (3 negative), samples with EGFR ex20ins. Baseline demographic and clinical characteristics were similar between the CHRYSALIS-, Guardant360 CDx–, and ODxT–identified populations. Agreement with local PCR/next-generation sequencing tests used for enrollment into CHRYSALIS demonstrated high adjusted negative (99.6% and 99.9%) and positive (100% for both) predictive values with the Guardant360 CDx and ODxT tests, respectively. Overall response rates were comparable between the CHRYSALIS, Guardant360 CDx, and ODxT populations. Both the plasma- and tissue-based diagnostic tests provided accurate, comprehensive, and complementary approaches to identifying patients with EGFR ex20ins who could benefit from amivantamab therapy. Mutations of the epidermal growth factor receptor gene (EGFR) are among the most frequent genetic alterations in non–small cell lung cancer (NSCLC). The targeting of EGFR-activating mutations with EGFR tyrosine kinase inhibitors (TKIs) has dramatically improved clinical outcomes and survival in some patients.1Ramalingam S.S. Vansteenkiste J. Planchard D. Cho B.C. Gray J.E. Ohe Y. Zhou C. Reungwetwattana T. Cheng Y. Chewaskulyong B. Shah R. 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Cho B.C. amivantamab in EGFR exon 20 insertion cell lung Thorac Oncol. 16: Full Text Full Text PDF Google Scholar on the data from that the use of amivantamab for the treatment of patients with EGFR ex20ins NSCLC that progressed on or after platinum-based chemotherapy approved by the US Food and Drug and the in The of companion diagnostics (CDx) that patients with genomic most to benefit are identified to the US Food and Drug has approved the use of CDx with for the treatment of patients with lung the and of in treatment last accessed January 19, In the CHRYSALIS study of patients with EGFR ex20ins were on local or sequencing testing of tumor or The bridging study the efficacy outcomes with amivantamab in patients with EGFR ex20ins identified local tests in the CHRYSALIS study and in those who been identified the Guardant360 CDx or the Oncomine Dx Target Test tumor The ongoing phase 1 CHRYSALIS study is the and efficacy of amivantamab in patients with advanced NSCLC and a of patients who harbor EGFR ex20ins last accessed January 19, with EGFR ex20ins were on local testing of tumor or testing to to with and validated Clinical or local This bridging study on the efficacy population from CHRYSALIS, which the 81 patients with EGFR ex20ins after on platinum-based chemotherapy, who were at the phase and who at or who or by the data Park K. N. P. Kim S. Lee J. Kim D. S. A. J. J. Lee Lee K.H. N. Yang T. K. Yang J.C. J. A. M. Cho B.C. amivantamab in EGFR exon 20 insertion cell lung Thorac Oncol. 16: Full Text Full Text PDF Google Scholar The of bridging study to the efficacy outcomes in patients who been identified by the Guardant360 CDx or ODxT to those in the efficacy population from the CHRYSALIS The point the overall response as response or P. J. L.H. D. R. J. S. S. M. L. L. L. R. D. J. response in guideline J Full Text Full Text PDF PubMed Scopus Google Scholar in guideline version as by of response a point of the plasma and tumor samples from patients in the CHRYSALIS efficacy population were used for CDx samples from patients with EGFR ex20ins mutations who were in the efficacy population were tested. samples by of the local tests used in the CHRYSALIS study were to the of CDx samples were to negative for EGFR ex20ins of samples is in Guardant360 CDx and Oncomine Dx Target samples were from patients who the for in the CHRYSALIS study from the ex20ins of as were samples from patients in the versus Lung study last accessed January 19, NSCLC tissue samples were and The bridging study approved by the from patients who were in the CHRYSALIS Guardant360 CDx is a in diagnostic that targeted for the of EGFR ex20ins tumor from the plasma of The of Guardant360 CDx EGFR ex20ins as in-frame insertion between and of the EGFR gene the of negative data from patients who from the ex20ins of the CHRYSALIS study as well as clinical data from the study were samples from the the ex20ins of and from the study were positive for EGFR ex20ins by local 19 patients with EGFR ex20ins from the CHRYSALIS study were in the analysis in the efficacy analysis Guardant360 CDx to the standard of the clinical S. B.C. M. R. D. Lee C.P. H. A. of a comprehensive cancer and 2018; PubMed Scopus Google Scholar ODxT is a in diagnostic that targeted to EGFR ex20ins from from tumor samples the Dx and of clinical by a to the and tumor or tumor the of the of tumor among the samples were that the ODxT Test for tumor and were tested. were from the and into an to the used for and in the sequencing and the were into that were to a by the on and and were for EGFR ex20ins on the ODxT Test the of negative NSCLC samples that were identified as negative by or testing were 18 patients with EGFR ex20ins from the CHRYSALIS study were in the analysis in the efficacy analysis at the ODxT to the The and the were used to demographic and characteristics between populations. The and are in patients with advanced NSCLC 12 from last platinum-based chemotherapy at the and progressed on or after platinum-based chemotherapy and who were positive by the CDx tests for EGFR ex20ins. of The used to the in in the populations. and the are and negative values were the local as the are for and negative predictive values with CDx were by of the positive and negative predictive values to an EGFR ex20ins of J.W. Gandara D.R. Frampton G.M. Madison R. Peled N. Bufill J.A. Dy G.K. Ou S.I. Stephens P.J. McPherson J.D. Lara Jr., P.N. Burich R.A. Ross J.S. Miller V.A. Ali S.M. Mack P.C. Schrock A.B. Diverse EGFR exon 20 insertions and co-occurring molecular alterations identified by comprehensive genomic profiling of NSCLC.J Thorac Oncol. 2018; 13: 1560-1568Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar of the adjusted positive and negative predictive were the point in which the The efficacy population from the CHRYSALIS study the 81 patients with EGFR ex20ins who were at the and progressed on or after platinum-based chemotherapy. and tissue samples from these patients were the Guardant360 and ODxT the 81 3 plasma samples for Guardant360 and among the 78 patients who were 62 were identified as EGFR ex20ins positive and as ex20ins negative ODxT samples were or the tumor tissue samples that were with 39 were EGFR ex20ins 3 were ex20ins and The demographic and characteristics were between the with EGFR ex20ins identified by local or ODxT all identified EGFR the 62 a of and of the patients were and Baseline tests CDx to to to of of to to to companion Oncomine Dx Target in a CDx, companion Oncomine Dx Target of the between the from the local and the CDx tests, the positive and negative values were samples with a CDx from multiple the CHRYSALIS efficacy population, patients with EGFR ex20ins who were of the efficacy population, samples from the and With a high positive and no were with and a the point for negative on the and for an EGFR ex20ins of J.W. Gandara D.R. Frampton G.M. Madison R. Peled N. Bufill J.A. Dy G.K. Ou S.I. Stephens P.J. McPherson J.D. Lara Jr., P.N. Burich R.A. Ross J.S. Miller V.A. Ali S.M. Mack P.C. Schrock A.B. Diverse EGFR exon 20 insertions and co-occurring molecular alterations identified by comprehensive genomic profiling of NSCLC.J Thorac Oncol. 2018; 13: 1560-1568Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar the adjusted negative predictive with Guardant360 and the adjusted positive predictive similar high of with with an adjusted positive predictive of and a negative predictive of the of EGFR a that a positive by ODxT or Guardant360 positive by a local that no for EGFR ex20ins were with between and Guardant360 CDx of Guardant360 CDx CDx companion negative overall positive in a between and ODxT of ODxT to to to negative Oncomine Dx Target overall positive in a CDx, companion negative overall positive negative Oncomine Dx Target overall positive The of the bridging study to clinically the CDx tests by comparable efficacy between the that been identified CDx and the identified local tests from the CHRYSALIS The of in the and in the were similar to the of in the CHRYSALIS efficacy population The rates of clinical as or response or for up to were comparable between the identified by local and tests CDx overall response response or benefit response or response and for at to two companion Oncomine Target response or response or response and for at to two in a CDx, companion Oncomine Target In the of patients who an response in the CHRYSALIS efficacy population, the In the of and 18 identified by Guardant360 and the were and In a combined analysis of CDx tests, the were in the identified by Guardant360 or ODxT and in the identified by CDx tests patients were negative by CDx The in the that positive by ODxT or by Guardant360 were and high of between the Guardant360 and ODxT tests a in ex20ins response or efficacy or Guardant360 and Guardant360 by Guardant360 CDx by companion epidermal growth factor exon 20 Oncomine Dx Target overall response response or in a between Guardant360 CDx and ODxT CDx tests were due to or tests were due to or companion Oncomine Dx Target tests were due to or in a CDx, companion epidermal growth factor exon 20 Oncomine Dx Target overall response CDx, companion Oncomine Dx Target patients with genomic who respond to targeted therapies is to that patients and clinically validated CDx that has been approved for use with a the selection of patients who benefit from This bridging study the efficacy of amivantamab in patients who been identified by two CDx tests, Guardant360 and with that in the efficacy population from the CHRYSALIS high of demonstrated between local tests and the two CDx tests in identifying patients with EGFR ex20ins. no were with The of the study with comparable in the identified by the local and ODxT the Guardant360 and ODxT CDx tests are clinically validated diagnostic tests that used for identifying patients for and use of amivantamab therapy. In the of a CDx for plasma- and tissue-based testing were testing of tumor samples tissue of which the in patients with advanced L. Tsao M.S. tissue for lung cancer in the of is for molecular J. 2014; PubMed Scopus Google Scholar In the of the tissue samples were or for testing with the ODxT the and selection of the for the molecular as a tissue the of the L. Tsao M.S. tissue for lung cancer in the of is for molecular J. 2014; PubMed Scopus Google Scholar, E. F. F. A. in the Clin Oncol. 2013; PubMed Scopus Google Scholar, M. S. M. J. D. E. P. N. A. P. I. B. S. A. D. K. C. C.R. M. A.C. B. G. L. G. M. J. P.A. C. and by Engl J Med. PubMed Scopus Google Scholar plasma testing is a and in which samples at multiple the of the all tumors into plasma or for J. N. H. M. A. The of for in cell lung Oncol. J.D. Oxnard G.R. C. M. P. Lindeman N. C.M. A.M. P. 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Li T. clinical outcomes for patients with NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations.J Thorac Oncol. 16: Full Text Full Text PDF Google Scholar The study by the of the of samples from populations. negative plasma and tumor tissue samples were for testing of the between the two CDx all of the tumor samples were of a for In the Guardant360 CDx and the tissue-based ODxT Test were clinically validated in bridging the use of the Guardant360 and ODxT CDx tests as an and complementary for the of patients for amivantamab with tests been approved by the US Food and Drug for use as a all of the patients who in and the and who for the patients as well as the at the clinical by and provided by Tracy T. and the and the and P.L. the and the of the to the of the