Guardant360 CDx Approved in Japan for Utilization in Advanced Solid Tumors

The Ministry of Health, Labour, and Welfare has approved Guardant360 CDx to perform comprehensive genomic profiling in patients with advanced solid cancers.

The Ministry of Health, Labour, and Welfare has approved Guardant360 CDx to perform comprehensive genomic profiling in patients with advanced solid cancers, according to an announcement from Guardant Health.1

The test was also approved for utilization as a companion diagnostic to select those with microsatellite instability–high (MSI-H) solid tumors who could derive benefit from pembrolizumab (Keytruda), as well as 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.”

In May 2017, the FDA granted an accelerated approval to pembrolizumab for use in adult and pediatric patients with unresectable or metastatic, MSI-H or mismatch repair deficient (dMMR) solid tumors that have progressed following treatment and who do not have satisfactory alternative therapeutic options available.2 The immunotherapy was also greenlit for use in those with MSI-H or dMMR CRC after progression on a fluoropyrimidine, oxaliplatin, and irinotecan.

The regulatory decision was based on findings from 149 patients with MSI-H or dMMR cancers who had been included in 5 single-arm clinical trials: KEYNOTE-016 (NCT01876511; n = 58), KEYNOTE-164 (NCT02460198; n = 61), KEYNOTE-012 (NCT01848834; n = 6), KEYNOTE-028 (NCT02054806; n = 5), and KEYNOTE-158 (NCT02628067; n = 19). Of those included, 90 patients had CRC and 59 had 1 of 14 other tumor types.

In these trials, pembrolizumab was given at a 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.

The median age among these patients was 55 years, and 36% were at least 65 years of age. Fifty-six percent of patients were male and 77% were White. Regarding ECOG performance status, 36% had a status of 0 and 64% had a status of 1. Moreover, 2% of patients had locally advanced, unresectable disease, and the majority (98%) had metastatic disease. In those with metastatic or unresectable disease, the median number of prior therapies received was 2. Notably, 84% of patients with metastatic CRC had previously received at least 2 lines of therapy vs 53% of those with other solid tumors.

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

Data from these trials indicated that pembrolizumab elicited an objective response rate (ORR) of 39.6% (95% CI, 31.7%-47.9%), which included a complete response (CR) rate of 7.4% and a partial response (PR) rate of 32.2%. Among the subset of patients with CRC, the immunotherapy induced an ORR of 36.0%; this rate was 46% in those with other tumor types.

Beyond CRC, patients with other tumor types who responded to treatment included those with 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).

The median duration of response (DOR) to pembrolizumab had not yet been reached (range, 1.6+ months to 22.7+ months). Among those who responded to the immunotherapy, 78% experienced a response that persisted for 6 months or longer.

The accelerated approval for the agent in this setting is contingent on results of a confirmatory trial.

Later the same year, in July 2017, the FDA granted an accelerated approval to nivolumab for use in adult and pediatric patients with MSI-H or dMMR metastatic CRC who had progressed after treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.3 This decision was based on findings from the phase 2 CheckMate-142 trial (NCT02060188).4

The open-label, international trial enrolled patients with recurrent or metastatic CRC, including those with MSI-H and microsatellite stable disease. These patients experienced disease progression during, after, or were intolerant to previous treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

Participants were randomized to receive either nivolumab monotherapy or nivolumab plus ipilimumab (Yervoy). The regulatory agency assessed a cohort of patients from the study (n = 74) who had MSI-H or dMMR disease who received at least 1 prior regimen for metastatic disease that contained fluoropyrimidine with oxaliplatin or irinotecan for metastatic disease. These patients were given nivolumab at 3 mg/kg every 2 weeks. Treatment was administered until intolerable toxicity or radiographic progression.

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

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

In those with dMMR/MSI-H metastatic disease, the median time to response was 2.8 months (interquartile range, 1.4-3.2) per investigator assessment. The median DOR to nivolumab had not yet been reached at the time of the analysis, which had a data cutoff date of January 3, 2017. Sixty-seven percent of patients (95% CI, 38%-88%) had responses last for at least 6 months. Eight patients experienced responses that persisted for 12 months or longer.

After 36 investigator-assessed progression events, the median PFS was 14.3 months (95% CI, 4.30–not estimable), with a 12-month PFS rate of 50% (95% CI, 38%-61%). The 12-month OS rate with nivolumab was 73% (95% CI, 62%-82%).

“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.”


  1. Guardant Health receives regulatory approval for Guardant360 CDx in Japan. News release. Guardant Health; March 14, 2022. Accessed March 16, 2022.
  2. 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 March 16, 2022.
  3. FDA grants nivolumab accelerated approval for MSI-H or dMMR colorectal cancer. News release. FDA; July 31, 2017. Accessed March 16, 2022.
  4. 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