FDA Approves FoundationOne Liquid CDx for Solid Tumors

The FDA has approved the FoundationOne Liquid CDx, a liquid biopsy for all solid tumors with multiple companion diagnostic indications.^1,2

The regulatory decision was based on analytical and clinical validation studies that collected over 7500 samples and 30,000 unique variants across more than 30 tumor types. When investigators analyzed the platform across these varied tumors, the test showed high sensitivity and specificity, even at the low allele frequencies that were noted in the collected blood samples.

The assay is intended to be utilized as a tool to help inform treatment decisions in accordance with FDA-approved labeling and professional guidance for patients with solid tumors. FoundationOne Liquid CDx will serve as a companion diagnostic to determine which patients will benefit from FDA-approved targeted therapies, including an indication for rucaparib (Rubraca), which recently received regulatory approval for use in select adult patients with BRCA1/2-mutated metastatic castration-resistant prostate cancer (mCRPC), and 3 frontline TKIs in non–small cell lung cancer.

“We believe that cancer patients and their physicians deserve the highest quality genomic testing to make informed decisions about personalized treatment,” Brian Alexander, MD, MPH, chief medical officer at Foundation Medicine, stated in a press release. “Created from our scientific expertise and pioneering spirit, FoundationOne Liquid CDx underscores our commitment to advance patient care across all cancer types by bringing forward multiple FDA-approved comprehensive genomic profiling options that are increasingly essential for high-quality cancer care.”

The liquid biopsy evaluated over 300 cancer-associated genes for aberrations and test results are delivered as part of an integrated report that determines alterations matched to FDA-approved treatments. The report also contains data regarding genomic signatures such as microsatellite instability and blood tumor mutational burden, in addition to single gene alterations to inform the use of other treatment approaches, like immunotherapy. Moreover, the report also includes relevant clinical trial information and content developed in agreement with professional guidelines for patients with any solid tumor.

“Tumors with BRCA mutations are by far the most responsive to PARP inhibitors in mCRPC, and when we started development of [rucaparib] for mCRPC, we knew it was important to develop a plasma-based companion diagnostic for physician and patient ease of use,” Patrick J. Mahaffy, president and CEO of Clovis Oncology, stated in a press release. “What we could not have foreseen was how important a plasma-based test would be in this COVID-19 environment, in which even important procedures, such as tissue-based biopsies, can be difficult to schedule for patients. We are pleased that the FDA approved a plasma-based companion diagnostic to identify [patients with] mCRPC who might benefit from treatment with [rucaparib].”

The objective response rate (ORR) in patients with BRCA­1/2-mutated mCRPC who received rucaparib in the ongoing phase 2 TRITON trial was 46% (95% CI, 31-63) per FoundationOne Liquid CDx, which was comparable to the 44% (95% CI, 31-57) reported with clinical trial assays for those enrolled on the trial; this highlights the utility and consistency of using a liquid biopsy assay for patient selection, according to Clovis Oncology, Inc.

In May 2020, the FDA granted rucaparib an accelerated approval for adult patients with BRCA-associated mCRPC who received prior treatment with androgen receptor–directed therapy and a taxane-based chemotherapy based on data from the TRITON.

The international, multicenter, open-label trial enrolled male patients with mCRPC linked with 1 of 13 homologous recombination repair gene alterations. Participants had progressed on androgen-receptor therapy and 1 prior taxane-based chemotherapy and they had an ECOG performance status of 0 or 1. Patients were excluded from the analysis if they had received previous treatment with a PARP inhibitor, mitoxantrone, cyclophosphamide, or platinum-based chemotherapy.³

Participants were given rucaparib at 600 mg twice daily until either radiographic progression or discontinuation of treatment. Investigators radiographically evaluated patients’ tumors every 8 weeks for the duration of 24 weeks, and then every 12 weeks thereafter. Prostate-specific antigen (PSA) assessments were also done every 4 weeks.

The primary end points of the trial were confirmed ORR per RECIST/Prostate Cancer Clinical Trials Working Group 3 criteria in those with measurable disease at baseline and PSA response in those who did not have measurable disease at baseline.

A total of 45 patients with BRCA1/2 mutations were determined to be evaluable for PSA response, while a total of 25 patients with BRCA1/2 mutations were evaluable for radiographic response.

Of the 45 evaluable patients with BRCA1/2 mutations, the median age was 71 years (range, 50-88); more than half of patients, or 62.2%, had an ECOG performance status of 1. Patients had received previous therapies such as abiraterone acetate (Zytiga; 55.6%), enzalutamide (Xtandi; 73.3%), both abiraterone and enzalutamide (31.1%), docetaxel (95.6%), cabazitaxel (Jevtana; 8.9%), sipuleucel-T (Provenge; 13.3%), and radium-223 dichloride (Xofigo; 11.1%).

Moreover, the majority of patients with BRCA1/2 mutations, or 88.9%, had bone metastases; 62.2% of patients had nodal metastases and 42.2% had visceral metastases. Additionally, 33.3% of patients had a germline BRCA1/2 mutation and 66.7% had a somatic BRCA1/2 mutation.

The preliminary results included information collected on 85 participants who were enrolled on the trial through June 29, 2018. At a median follow-up of 5.7 months, results indicated that rucaparib elicited a 44% confirmed ORR (95% CI, 24.4%-65.1%) per investigator assessment among evaluable men with BRCA1/2-mutated disease. Of patients with BRCA1/2 alterations, 51.1% achieved a confirmed PSA response to rucaparib.

All 11 investigator-assessed radiographic responses reported in the patients with BRCA-mutated tumors were partial responses (PRs) and 9 patients (36.0%) had stable disease. The median duration of response had not been reached.

Updated data were presented at the 2019 ESMO Congress. At a median follow-up of 13.1 months (range, 4.1-28.5), data showed that the agent elicited a 43.9% confirmed ORR and a confirmed PSA response of 52.0% in patients with mCRPC whose tumors harbored a BRCA1/2 mutation.⁴ Notably, these responses proved to be durable, with more than half, or 60%, lasting for 24 weeks or longer.

With regard to safety, all-grade treatment-emergent adverse effects reported in more than 20% of patients included asthenia/fatigue (55.3%), nausea (49.5%), anemia/decreased hemoglobin (37.9%), decreased appetite (27.9%), transient increased aspartate transaminase/alanine aminotransferase (24.7%), constipation (24.7%), vomiting (22.1%), and diarrhea (21.1%).

“Now that we have drugs that specifically benefit patients with BRCA mutations, the ability to identify who has these mutations is paramount,” Celestia S. Higano, MD, FACP, of the University of Washington School of Medicine, added in the release. “In contrast to tissue biopsy, a liquid biopsy is a blood-plasma test that is less invasive than a tissue biopsy for assessing germline or somatic BRCA mutations. The FDA’s approval of liquid biopsy tests represents a significant advancement for clinicians and patients to make timely decisions about treatment options.”

FoundationOne Liquid CDx is expected to become commercially available on August 28, 2020. The test will be covered across all solid tumors for eligible Medicare and Medicare Advantage beneficiaries per the Centers for Medicare and Medicaid Services National Coverage Decision Memo criteria.

References

1. FDA approves FoundationOne Liquid CDx to serve as Rubraca (rucaparib) companion diagnostic to identify eligible patients with BRCA1/2-mutant, metastatic castration-resistant prostate cancer (mCRPC). News release. Clovis Oncology, Inc. August 26, 2020. Accessed August 26, 2020. https://bwnews.pr/2EEVIMm.
2. FDA approves Foundation Medicine’s FoundationOne Liquid CDx, a comprehensive pan-tumor liquid biopsy test with multiple companion diagnostic indications for patients with advanced cancer. News release. Foundation Medicine. August 26, 2020. Accessed August 26, 2020. https://bit.ly/2EtxNQs.

• Clovis Oncology highlights Rubraca (rucaparib) updated data from the ongoing TRITON2 clinical trial in patients with mCRPC and exploratory and integrated analyses in recurrent ovarian cancer at the ESMO Congress 2019. News release. Clovis Oncology, Inc. September 29, 2019. Accessed August 26, 2020. https://bit.ly/2u4iEPS.
• Abida W, Bryce AH, Vogelzang NJ, et al. Preliminary results from TRITON2: a phase 2 study of rucaparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination repair (HRR) gene alterations. Ann Oncol. 2018;29(suppl_8):viii271-viii302. doi: 10.1093/annonc/mdy284