Guardant360 CDx Receives Approval for Use in Advanced Solid Tumors in Japan


Regulatory approval has been granted for Guardant360 in Japan and will offer tumor mutation profiling and companion diagnostics for therapies in patients with solid tumors which have KRAS G12C or MSI-H status.

Guardant360 CDx has been approved by the Ministry of Health, Labor, and Welfare to perform comprehensive genomic profiling in patients with advanced solid cancers, according to Guardant Health.1

The CDx was also granted approval to be used as a companion diagnostic to select those with microsatellite instability–high (MSI-H) solid tumors who could benefit from treatment with pembrolizumab (Keytruda), in addition to patients with MSI-high advanced colorectal cancer (CRC) who could benefit from treatment with nivolumab (Opdivo).

“We are delighted to receive regulatory approval in Japan for the Guardant360 CDx test. We strongly believe that our liquid biopsy test will help to enhance the quality of cancer management in Japan by offering tumor mutation profiling and companion diagnostics for therapies in patients whose tumors have KRAS G12C or MSI-H status,” Simranjit Singh, chief executive officer of Guardant Health AMEA and representative director of Guardant Health Japan, stated in a press release. “One of the key benefits of our liquid biopsy test is that it enables physicians to match patients to appropriate treatment quickly without the complications and delays of a tissue biopsy.”

Guardant360 CDx, a liquid biopsy test which helps guide treatment decisions for patients with advanced-stage cancer, was the first of its kind to receive approval from the FDA in August 2020 for comprehensive tumor mutation profiling across all solid cancers.2

Back in May 2017, the FDA granted approval to pembrolizumab for use in both adult and pediatric patients with unresectable or metastatic, MSI-H or mismatch repair deficient (dMMR) solid tumors.3 The approval could be used in individuals whose tumors had progressed following treatment and those who do not have satisfactory alternative therapeutic options available. The immunotherapy was also approved for use in patients with MSI-H or dMMR CRC after progression on fluoropyrimidine, oxaliplatin, and irinotecan.

This decision was based on results of 5 single-arm clinical trials: KEYNOTE-016 (NCT01876511), KEYNOTE-164 (NCT02460198), KEYNOTE-012 (NCT01848834), KEYNOTE-028 (NCT02054806), and KEYNOTE-158 (NCT02628067).

A total of 149 patients with MSI-H or dMMR cancers were enrolled across the 5 trials. Of the participants, 90 had CRC and 59 had 1 of 14 other tumor types. Within these trials, pembrolizumab was given at the recommended dose of 200 mg every 3 weeks or 10 mg/kg every 2 weeks until progressive disease, intolerable toxicity, or a maximum of 24 months.

Among the enrolled participants, the median age was 55 years, 56% of patients were male and 77% were White. Thirty-six percent of patients had an ECOG performance status of 0 and 64% had a status of 1. Additionally, 2% of patients had locally advanced, unresectable disease, and 98% had metastatic disease. Of those who had metastatic or unresectable disease, the median number of prior therapies received was 2, and in patients with metastatic CRC, 84% had received at least 2 prior lines of therapy versus 53% in patients with other solid tumors.

Among the 149 patients, 135 had MSI-H or dMMR tumor status determined with IHC tests for dMMR or laboratory-developed, investigational polymerase chain reaction (PCR) tests for MSI-H status. The remaining 14 participants’ MSI-H status was determined through a retrospective evaluation of 415 tumor samples using a central laboratory-developed PCR test. Forty-seven patients were found to have dMMR cancer per IHC, 60 patients had MSI-H disease per PCR, and 42 patients were identified with both tests.

Findings revealed pembrolizumab to elicit an objective response rate (ORR) of 39.6% (95% CI, 31.7%-47.9%), including a complete response (CR) rate of 7.4% and a partial response (PR) rate of 32.2%. The immunotherapy induced an ORR of 36.0% in patients with CRC, and 46% in patients with other tumor types.

Patients who had other tumor types and responded to treatment included diagnoses of endometrial cancer (n = 5), biliary cancer (n = 3), gastric or gastroesophageal junction cancer (n = 5), pancreatic cancer (n = 5), small intestinal cancer (n = 3), breast cancer (n = 2), prostate cancer (n = 1), esophageal cancer (n = 1), retroperitoneal adenocarcinoma (n = 1), and small cell lung cancer (n = 1).

Median duration of response (DOR) to pembrolizumab had not yet been reached (range, 1.6+ to 22.7+). A response which persisted for 6 months or longer was experienced by 78% of those who responded to the immunotherapy.

“Guardant Health Japan is dedicated to bringing innovative and comprehensive liquid biopsy tests such as Guardant CDx to Japan so that patients with advanced stage cancer can benefit from genomic profiling information,” Gen Asano, general manager of Guardant Health Japan, added in the press release. “This regulatory approval has been made possible because of the collaborations we have with leading cancer experts in Japan.”

In July 2017, the same year as the accelerated approval of pembrolizumab, the FDA also granted accelerated approval to nivolumab to treat adult and pediatric patients with MSI-H or dMMR metastatic CRC who had progressed after treatment with fluoropyrimidine, oxaliplatin, and irinotecan, based on findings from the open-label, international, phase 2 CheckMate-142 trial (NCT02060188).4,5

CheckMate-142 enrolled patients 18 years or older with recurrent or metastatic CRC, including those with MSI-H and microsatellite stable disease who experienced disease progression during, after, or were intolerant to previous treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

Participants were randomized and received either nivolumab monotherapy or nivolumab plus ipilimumab (Yervoy). Patients were given nivolumab at 3 mg/kg every 2 weeks and treatment was administered until intolerable toxicity or radiographic progression.

ORR per investigator assessment was the primary end point of the trial with secondary end points including safety and tolerability, progression-free survival (PFS) based on investigator and blinded independent central review assessments, overall survival (OS), the association between biomarkers like PD-L1 expression and nivolumab activity, and quality of life.

Findings revealed that in the 53 patients who previously received fluoropyrimidine, oxaliplatin, and irinotecan, nivolumab induced an ORR of 28.0% (95% CI, 17%-42%) per independent radiographic review committee using RECIST v1.1 criteria, including 1 CR and 14 PRs. Among the 74 participants in the overall population the ORR achieved with nivolumab was 32% per blinded independent central review (95% CI, 22%-44%).

The median time to response was 2.8 months (interquartile range, 1.4-3.2) per investigator assessment in participants with dMMR/MSI-H metastatic disease. Median DOR to nivolumab was not reached at the time of the analysis, and 67% of patients (95% CI, 38%-88%) had responses that lasted for at least 6 months.

Additionally, 8 patients experienced responses that persisted for 12 months or longer. The median PFS was 14.3 months (95% CI, 4.30–not estimable) after 36 investigator-assessed progression events, and the 12-month PFS rate was 50% (95% CI, 38%-61%). The 12-month OS rate with nivolumab was 73% (95% CI, 62%-82%).

  1. Guardant Health receives regulatory approval for Guardant360 CDx in Japan. News release. Guardant Health; March 14, 2022. Accessed April 5, 2022.
  2. Guardant Health Guardant360 CDx first FDA-approved liquid biopsy for comprehensive tumor mutation profiling across all solid cancers; August 07, 2020. Accessed April 5, 2022.
  3. FDA approves Merck’s KEYTRUDA (pembrolizumab) for adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient cancer. News release. Merck; May 23, 2017. Accessed April 5, 2022.
  4. FDA grants nivolumab accelerated approval for MSI-H or dMMR colorectal cancer. News release. FDA; July 31, 2017. Accessed April 5, 2022.
  5. Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18(9):1182-1191. doi:10.1016/S1470-2045(17)30422-9
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