REMARRY and PURSUIT trials: liquid biopsy-guided rechallenge with anti-epidermal growth factor receptor (EGFR) therapy with panitumumab plus irinotecan for patients with plasma RAS wild-type metastatic colorectal cancer
Abstract Background Previous clinical trials have demonstrated the potential efficacy of rechallenge with anti- epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) for patients with RAS/BRAF V600E wild-type metastatic colorectal cancer (mCRC). Moreover, post hoc biomarker analyses o...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-06-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-021-08395-2 |
| _version_ | 1819012296511324160 |
|---|---|
| author | Hiromichi Nakajima Daisuke Kotani Hideaki Bando Takeshi Kato Eiji Oki Eiji Shinozaki Yu Sunakawa Kentaro Yamazaki Satoshi Yuki Yoshiaki Nakamura Takeharu Yamanaka Takayuki Yoshino Takashi Ohta Hiroya Taniguchi Yoshinori Kagawa |
| author_facet | Hiromichi Nakajima Daisuke Kotani Hideaki Bando Takeshi Kato Eiji Oki Eiji Shinozaki Yu Sunakawa Kentaro Yamazaki Satoshi Yuki Yoshiaki Nakamura Takeharu Yamanaka Takayuki Yoshino Takashi Ohta Hiroya Taniguchi Yoshinori Kagawa |
| author_sort | Hiromichi Nakajima |
| collection | DOAJ |
| description | Abstract Background Previous clinical trials have demonstrated the potential efficacy of rechallenge with anti- epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) for patients with RAS/BRAF V600E wild-type metastatic colorectal cancer (mCRC). Moreover, post hoc biomarker analyses of clinical trials has suggested that RAS status in circulating tumor DNA (ctDNA) has a high probability to select patients who could benefit from anti-EGFR mAb rechallenge. Methods This trial is composed of 2 phases: a monitoring phase (REMARRY) and a trial phase (PURSUIT). A monitoring phase, the REMARRY study, aims to evaluate the dynamics of plasma RAS status during the subsequent treatments after refractory to anti-EGFR therapy in patients with mCRC with RAS/BRAF V600E wild-type tumors who have progressed after a response to previous anti-EGFR therapy, using a highly sensitive digital polymerase chain reaction OncoBEAM RAS CRC kit in a central laboratory (Sysmex, Japan). A trial phase, the PURSUIT trial, is a multicenter, single-arm phase II trial to assess the efficacy and safety of rechallenge therapy with panitumumab plus irinotecan in patients without RAS mutations in ctDNA (plasma RAS negative) in the REMARRY study. Key eligibility criteria of the PURSUIT trial include RAS/BRAF V600E wild-type mCRC in tumor tissue refractory or intolerant to fluoropyrimidine, oxaliplatin, and irinotecan; progression after complete or partial response to previous anti-EGFR therapy; plasma RAS negative (defined as plasma mutant allele frequencies [MAF] of all RAS ≤ 0.1%) within 28 days prior to enrollment; 4 months or more between the last administration of previous anti-EGFR mAb and the start of protocol treatment; and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1. The primary endpoint is the confirmed objective response rate (ORR). The target sample size of the PURSUIT trial is 50 patients. Biomarker analyses will be performed in parallel using the OncoBEAM RAS CRC kit and a next-generation sequencing-based ctDNA analysis (Guardant360). Discussion Our trial aims to confirm the clinical benefit of anti-EGFR mAb rechallenge therapy in patients with plasma RAS negative. Moreover, through biomarker analyses, our trial will shed light on which patients would benefit from rechallenge in addition to being plasma RAS negative. Trial registration The REMARRY study: UMIN, UMIN000036424 . Registered date: April 5, 2019. The PURSUIT trial: jRCT, jRCTs031190096 . Registered date: October 1, 2019. |
| first_indexed | 2024-12-21T01:41:48Z |
| format | Article |
| id | doaj.art-02b244cb3c0549f99cadc14324637692 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-21T01:41:48Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-02b244cb3c0549f99cadc143246376922022-12-21T19:20:08ZengBMCBMC Cancer1471-24072021-06-012111610.1186/s12885-021-08395-2REMARRY and PURSUIT trials: liquid biopsy-guided rechallenge with anti-epidermal growth factor receptor (EGFR) therapy with panitumumab plus irinotecan for patients with plasma RAS wild-type metastatic colorectal cancerHiromichi Nakajima0Daisuke Kotani1Hideaki Bando2Takeshi Kato3Eiji Oki4Eiji Shinozaki5Yu Sunakawa6Kentaro Yamazaki7Satoshi Yuki8Yoshiaki Nakamura9Takeharu Yamanaka10Takayuki Yoshino11Takashi Ohta12Hiroya Taniguchi13Yoshinori Kagawa14Department of Gastrointestinal Oncology, National Cancer Center Hospital EastDepartment of Gastrointestinal Oncology, National Cancer Center Hospital EastDepartment of Clinical Oncology, Aichi Cancer Center HospitalDepartment of Surgery, National Hospital Organization Osaka National HospitalDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Gastroenterology, The Cancer Institute Hospital of the Japanese Foundation for Cancer ResearchDepartment of Clinical Oncology, St. Marianna University School of MedicineDivison of Gastrointestinal Oncology, Shizuoka Cancer CenterDepartment of Gastroenterology and Hepatology, Hokkaido University HospitalDepartment of Gastrointestinal Oncology, National Cancer Center Hospital EastDepartment of Biostatistics, Yokohama City University School of MedicineDepartment of Gastrointestinal Oncology, National Cancer Center Hospital EastDepartment of Clinical Oncology, Kansai Rosai HospitalDepartment of Gastrointestinal Oncology, National Cancer Center Hospital EastDepartment of Colorectal Surgery, Osaka General Medical CenterAbstract Background Previous clinical trials have demonstrated the potential efficacy of rechallenge with anti- epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) for patients with RAS/BRAF V600E wild-type metastatic colorectal cancer (mCRC). Moreover, post hoc biomarker analyses of clinical trials has suggested that RAS status in circulating tumor DNA (ctDNA) has a high probability to select patients who could benefit from anti-EGFR mAb rechallenge. Methods This trial is composed of 2 phases: a monitoring phase (REMARRY) and a trial phase (PURSUIT). A monitoring phase, the REMARRY study, aims to evaluate the dynamics of plasma RAS status during the subsequent treatments after refractory to anti-EGFR therapy in patients with mCRC with RAS/BRAF V600E wild-type tumors who have progressed after a response to previous anti-EGFR therapy, using a highly sensitive digital polymerase chain reaction OncoBEAM RAS CRC kit in a central laboratory (Sysmex, Japan). A trial phase, the PURSUIT trial, is a multicenter, single-arm phase II trial to assess the efficacy and safety of rechallenge therapy with panitumumab plus irinotecan in patients without RAS mutations in ctDNA (plasma RAS negative) in the REMARRY study. Key eligibility criteria of the PURSUIT trial include RAS/BRAF V600E wild-type mCRC in tumor tissue refractory or intolerant to fluoropyrimidine, oxaliplatin, and irinotecan; progression after complete or partial response to previous anti-EGFR therapy; plasma RAS negative (defined as plasma mutant allele frequencies [MAF] of all RAS ≤ 0.1%) within 28 days prior to enrollment; 4 months or more between the last administration of previous anti-EGFR mAb and the start of protocol treatment; and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1. The primary endpoint is the confirmed objective response rate (ORR). The target sample size of the PURSUIT trial is 50 patients. Biomarker analyses will be performed in parallel using the OncoBEAM RAS CRC kit and a next-generation sequencing-based ctDNA analysis (Guardant360). Discussion Our trial aims to confirm the clinical benefit of anti-EGFR mAb rechallenge therapy in patients with plasma RAS negative. Moreover, through biomarker analyses, our trial will shed light on which patients would benefit from rechallenge in addition to being plasma RAS negative. Trial registration The REMARRY study: UMIN, UMIN000036424 . Registered date: April 5, 2019. The PURSUIT trial: jRCT, jRCTs031190096 . Registered date: October 1, 2019.https://doi.org/10.1186/s12885-021-08395-2Metastatic colorectal cancerCirculating tumor DNALiquid biopsyRechallengeAnti-EGFR mAb |
| spellingShingle | Hiromichi Nakajima Daisuke Kotani Hideaki Bando Takeshi Kato Eiji Oki Eiji Shinozaki Yu Sunakawa Kentaro Yamazaki Satoshi Yuki Yoshiaki Nakamura Takeharu Yamanaka Takayuki Yoshino Takashi Ohta Hiroya Taniguchi Yoshinori Kagawa REMARRY and PURSUIT trials: liquid biopsy-guided rechallenge with anti-epidermal growth factor receptor (EGFR) therapy with panitumumab plus irinotecan for patients with plasma RAS wild-type metastatic colorectal cancer BMC Cancer Metastatic colorectal cancer Circulating tumor DNA Liquid biopsy Rechallenge Anti-EGFR mAb |
| title | REMARRY and PURSUIT trials: liquid biopsy-guided rechallenge with anti-epidermal growth factor receptor (EGFR) therapy with panitumumab plus irinotecan for patients with plasma RAS wild-type metastatic colorectal cancer |
| title_full | REMARRY and PURSUIT trials: liquid biopsy-guided rechallenge with anti-epidermal growth factor receptor (EGFR) therapy with panitumumab plus irinotecan for patients with plasma RAS wild-type metastatic colorectal cancer |
| title_fullStr | REMARRY and PURSUIT trials: liquid biopsy-guided rechallenge with anti-epidermal growth factor receptor (EGFR) therapy with panitumumab plus irinotecan for patients with plasma RAS wild-type metastatic colorectal cancer |
| title_full_unstemmed | REMARRY and PURSUIT trials: liquid biopsy-guided rechallenge with anti-epidermal growth factor receptor (EGFR) therapy with panitumumab plus irinotecan for patients with plasma RAS wild-type metastatic colorectal cancer |
| title_short | REMARRY and PURSUIT trials: liquid biopsy-guided rechallenge with anti-epidermal growth factor receptor (EGFR) therapy with panitumumab plus irinotecan for patients with plasma RAS wild-type metastatic colorectal cancer |
| title_sort | remarry and pursuit trials liquid biopsy guided rechallenge with anti epidermal growth factor receptor egfr therapy with panitumumab plus irinotecan for patients with plasma ras wild type metastatic colorectal cancer |
| topic | Metastatic colorectal cancer Circulating tumor DNA Liquid biopsy Rechallenge Anti-EGFR mAb |
| url | https://doi.org/10.1186/s12885-021-08395-2 |
| work_keys_str_mv | AT hiromichinakajima remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer AT daisukekotani remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer AT hideakibando remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer AT takeshikato remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer AT eijioki remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer AT eijishinozaki remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer AT yusunakawa remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer AT kentaroyamazaki remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer AT satoshiyuki remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer AT yoshiakinakamura remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer AT takeharuyamanaka remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer AT takayukiyoshino remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer AT takashiohta remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer AT hiroyataniguchi remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer AT yoshinorikagawa remarryandpursuittrialsliquidbiopsyguidedrechallengewithantiepidermalgrowthfactorreceptoregfrtherapywithpanitumumabplusirinotecanforpatientswithplasmaraswildtypemetastaticcolorectalcancer |