Study Shows Guardant360 Liquid Biopsy Predicts Response to Pembrolizumab-Based Immunotherapy in Patients with Metastatic Non-Small Cell Lung Cancer

Rhea-AI Summary

A study published in JCO Precision Oncology demonstrates that the Guardant360^® liquid biopsy test effectively indicates treatment response in patients with metastatic non-small cell lung cancer (mNSCLC) undergoing pembrolizumab-based therapy. In a study involving 51 patients, molecular responders experienced significantly improved progression-free survival (14.1 months) and overall survival (22.1 months) versus non-responders. Guardant Health's test analyzes DNA from blood samples to guide treatment decisions, addressing the need for early indications of therapeutic efficacy.

Positive

• Molecular responders achieved progression-free survival of 14.1 months versus 4.4 months for non-responders.
• Overall survival was 22.1 months for molecular responders compared to 12.0 months for non-responders.
• Guardant360 test is covered by Medicare for advanced solid tumors, enhancing potential user base.

Negative

• A limited subset of patients with mNSCLC respond to pembrolizumab-based therapy, highlighting the need for alternative treatments.

For patients with metastatic non-small cell lung cancer (mNSCLC), not harboring an actionable mutation, immunotherapy is often recommended for first-line treatment. A new study in JCO Precision Oncology shows the Guardant360^® liquid biopsy test provides an early indication of treatment response to pembrolizumab-based immunotherapy by detecting molecular response or changes in circulating tumor DNA (ctDNA) levels early on.¹⁰ The study was led by researchers at the Perelman School of Medicine at the University of Pennsylvania.

The single-center, prospective, observational study evaluated molecular response in patients with mNSCLC (n=51) receiving pembrolizumab-based therapy, as monotherapy or with chemotherapy, as first- or second-line treatment. Changes in ctDNA were evaluated from baseline to nine weeks post-therapy initiation, and correlated with clinical and radiographic response.

In the study, the Guardant360 test showed that molecular responders achieved improved durable clinic benefit (log mean 49.4% vs. 3.5%) and significantly longer progression-free survival (median 14.1 vs. 4.4 months) and overall survival (median 22.1 vs. 12.0 months) compared to non-molecular responders. Molecular response was also associated with radiologic response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) .

“Unfortunately, only a subset of patients with metastatic non-small cell lung cancer will respond to pembrolizumab-based therapy, and their failure to achieve clinical benefit becomes evident after their disease has progressed,” said Helmy Eltoukhy, Guardant Health CEO. “This study adds to the growing body of evidence showing that our Guardant360 test can effectively measure molecular response, giving clinicians an earlier indication whether to continue or stop treatment, explore other therapeutic regimens, or enroll the patient in a clinical trial.”

The Guardant360 test is used to guide treatment in metastatic non-small cell lung cancer as the number of treatment-relevant genomic alterations continues to grow. Using next-generation sequencing, Guardant360 analyzes 83 genes using cell-free tumor DNA from blood samples. The Guardant360 test is broadly covered by Medicare for use across the vast majority of advanced solid tumors, including patients with metastatic non-small cell lung cancer. Last year, the FDA approved the Guardant360 CDx for tumor mutation profiling, also known as comprehensive genomic profiling (CGP), in patients with any solid malignant neoplasm (cancerous tumor).

"These are exciting results that further support the value of liquid biopsies as a noninvasive tool to measure early treatment responses by evaluating molecular response or changes in circulating tumor DNA," said Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence at Penn’s Perelman School of Medicine and Abramson Cancer Center "We look forward to additional studies to help make this approach a reality in the clinical setting to personalize immunotherapy based treatment decisions for patients with metastatic non-small cell lung cancer."

The publication, titled “Serial Monitoring of Circulating Tumor DNA by Next-Generation Gene Sequencing as a Biomarker of Response and Survival in Patients With Advanced NSCLC Receiving Pembrolizumab-Based Therapy,” can be found here: doi.org/10.1200/PO.20.00321.

About Guardant Health

Guardant Health is a leading precision oncology company focused on helping conquer cancer globally through use of its proprietary blood tests, vast data sets, and advanced analytics. The Guardant Health oncology platform leverages capabilities to drive commercial adoption, improve patient clinical outcomes, and lower healthcare costs across all stages of the cancer care continuum. Guardant Health has commercially launched liquid biopsy-based Guardant360^®, Guardant360 CDx, and GuardantOMNI^® tests for advanced stage cancer patients, and Guardant Reveal^™ test for early-stage cancer patients. These tests fuel development of its LUNAR screening program, which aims to address the needs of asymptomatic individuals eligible for cancer screening and individuals at a higher risk for developing cancer with early detection.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of federal securities laws, including statements regarding the potential scope, impact or benefit of Guardant Health liquid biopsies which involve risks and uncertainties that could cause the actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on current expectations, forecasts and assumptions, and actual outcomes and results could differ materially from these statements due to a number of factors. These and additional risks and uncertainties that could affect Guardant Health’s financial and operating results and cause actual results to differ materially from those indicated by the forward-looking statements made in this press release include those discussed under the captions “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operation” and elsewhere in its Annual Report on Form 10-K for the year ended December 31, 2020 as well as in its other reports filed with the Securities and Exchange Commission, including, when filed, its Quarterly Report on Form 10-Q for the period ended March 31, 2021. The forward-looking statements in this press release are based on information available to Guardant Health as of the date hereof, and Guardant Health disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing Guardant Health’s views as of any date subsequent to the date of this press release.

REFERENCES

1. Raja R, Kuziora M, Philip Z. Brohawn PZ, et al. Early Reduction in ctDNA Predicts Survival in Patients with Lung and Bladder Cancer Treated with Durvalumab. Clin Cancer Res; 2018: 24(24): 6212-6222. DOI: 10.1158/1078-0432.CCR-18-0386.

2. Aggarwal C,Thompson JC, Chien A, et al. Dynamic monitoring of circulating tumor DNA next-generation gene sequencing as a predictive biomarker of response and progression-free survival after pembrolizumab monotherapy in patients with advanced NSCLC. J Clin Oncol; 2019: 37:15 suppl, 3040-3040. DOI:10.1200/JCO.2019.37.15.

3. Kim ST, Cristescu R, Bass AJ, et al. Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med; 2018: 24(9):1449-1458. DOI: 10.1038/s41591-018-0101-z.

4. Shaw AT, Martini JF, Besse B, et al. Early circulating tumor (ct)DNA dynamics and efficacy of lorlatinib in patients (pts) with advanced ALK-positive non-small cell lung cancer (NSCLC). J Clin Oncol; 2019: 37:15_suppl, 9019-9019. DOI: 10.1200/JCO.2019.37.15.

5. Pascual J, Cutts RJ, Kingston B, et al. Assessment of early ctDNA dynamics to predict efficacy of targeted therapies in metastatic breast cancer: Results from plasmaMATCH trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-02.DOI: 10.1158/1538-7445.SABCS20-PS5-02.

6. Mack PC, Redman MW, Moon J, et al. Residual circulating tumor DNA (ctDNA) after two months of therapy to predict progression-free and overall survival in patients treated on S1403 with afatinib +/- cetuximab. J Clin Oncol; 2020: 38:15_suppl, 9532-9532. DOI: 10.1200/JCO.2020.38.15.

7. Maron SB, Chatila WK, Millang BM, et al, Pembrolizumab with trastuzumab and chemotherapy (PTC) in HER2-positive metastatic esophagogastric cancer (mEG): Plasma and tumor-based biomarker analysis. J Clin Oncol; 2020: 38:15_suppl, 4559-4559. DOI: 10.1200/JCO.2020.38.15.

8. Modi S, Park H, Murthy RK, et al. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study. J Clin Oncol; 2020: 38(17):1887-1896. DOI: 10.1200/JCO.19.02318.

9. Zhang Q, Luo J, Wu S, et al. Prognostic and Predictive Impact of Circulating Tumor DNA in Patients with Advanced Cancers Treated with Immune Checkpoint Blockade. Cancer Discov; 2020: 10:12, 1842-1853. DOI: 10.1158/2159-8290.CD-20-0047.

10. Thompson JC, Carpenter EL, Silva BA, et al. Serial Monitoring of Circulating Tumor DNA by Next-Generation Gene Sequencing as a Biomarker of Response and Survival in Patients With Advanced NSCLC Receiving Pembrolizumab-Based Therapy. JCO Precis; 2021: 5, 510-524. DOI: 10.1200/PO.20.00321.

Source: Guardant Health, Inc.

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FAQ

What does the new Guardant360 study reveal about pembrolizumab treatment in mNSCLC?

The study shows that the Guardant360 test can indicate early treatment response, correlating ctDNA levels with clinical outcomes.

How does the Guardant360 test improve treatment for metastatic non-small cell lung cancer?

The test provides early molecular response assessments, allowing for timely treatment adjustments in patients.

What were the survival rates for molecular responders in the Guardant360 study?

Molecular responders experienced a median progression-free survival of 14.1 months and overall survival of 22.1 months.

When was the Guardant360 study published?

The study was published in JCO Precision Oncology.

What are the implications of the Guardant360 test for patients with mNSCLC?

It offers clinicians a tool to determine whether to continue, stop treatment, or explore clinical trials based on early molecular responses.