NEW YORK – With a pan-cancer local coverage determination for its Guardant360 test now finalized and US Food and Drug Administration approval anticipated in the first half of this year, Guardant Health has settled the major regulatory and reimbursement hurdles for its non-invasive advanced cancer genotyping and can now accelerate its efforts in cancer screening and early-stage adjuvant testing, and focus on new companion diagnostic associations for its flagship test.
As part of this shift, Guardant announced this January at the JP Morgan Healthcare Conference a collaboration with NRG Oncology for a randomized trial called NRG-GI005 COBRA, which will enroll over 1,400 Stage II colon cancer patients. The trial will track these patients' outcomes to see whether using of Guardant's multi-omic Lunar test to guide post-surgery adjuvant treatment decisions offers an improvement over current standard of care.
In addition to that trial, Guardant said Monday that it will also be working this year on a second prospective interventional study for Lunar in the adjuvant setting, this one with Stand Up 2 Cancer (SU2C), Massachusetts General Hospital, and Dana-Farber Cancer Institute.
These two trials join an ongoing 24-month, prospective colorectal cancer screening study for the same assay technology, called ECLIPSE, which aims to enroll around 10,000 individuals who are at average risk of colorectal cancer and undergoing colonoscopy.
Although Guardant's plans for these two programs that it calls Lunar-1 and Lunar-2 have been in the works now for some time, the firm has previously been dividing its attention between early cancer detection and achieving a critical mass of clinical validity and utility data to insure a path to adoption for Guardant360.
The finalization last December of the pan-cancer local coverage determination for the test by Medicare contractor Palmetto GBA closed one of these doors, and FDA approval this year should shut the other, executives said this week.
During a call discussing its firm's Q4 2019 financial results, Guardant fielded questions about its discussions with FDA and whether there might be a delay from what the company previously said was an expectation for approval in the first half of this year.
President and COO AmirAli Talasaz said that because the premarket approval application Guardant has submitted to FDA is for a first-of-its-kind test "the process is a bit unpredictable." For example, the company recently had to furnish an "additional data package … based on questions and requests from the agency," he said. Despite this, Guardant remains "very confident that the discussions are going in the right direction," and its previously stated expected timeline still holds.
Once the test receives FDA approval, Guardant360 would be covered not only under the Palmetto pan-cancer LCD, but also under Medicare's national coverage determination for comprehensive next-gen sequencing assays. CEO Helmy Eltoukhy said, though, that the company sees FDA approval and the ability to leverage the NCD as offering only "marginal improvement" over the impact of the December LCD finalization. That said, he added, it'll "certainly help in terms of conversations with private payors and especially some of the laggards that are there."
"I think even more so it'll help with the middle majority and late majority [adopters] in the market in terms of really being that stamp of quality," Eltoukhy added. "We're still very much in the early innings of adoption right now. And when you look at comprehensive genomic testing rates … they're fairly low. They are still below 25 percent of the market whether it's tissue or liquid, and there's still a lot more work to do to [increase adoption]."
As the company now turns away from these longstanding hurdles for Guardant360 in the cancer early detection and adjuvant testing space, Talasaz said that Guardant is "very happy" with how the ECLIPSe screening trial has begun, ramping up now to over 70 sites.
Although the trial has a timeline of about 24 months, so won't finish during this year, he said that because of the structure, the period from final recruitment to data lock up should be very quick.
For COBRA, the company is still working out when it might start to analyze and report results. "It's a major program in collaboration with a major network and CRO, so we … still need a little bit more time before putting some specific timelines out there of when that study would end," Talasaz said.
The newly announced second study with SU2C will be similar to COBRA, but focused on stage III, rather than stage II colorectal cancers.
All three efforts are designed to validate the clinical utility of the Lunar assay in their respective settings, and, if successful, could play a pivotal role in supporting potential FDA approval and Medicare coverage, according to Guardant.
Talasaz added that the post-pan-cancer LCD and post-FDA period for Guardant is also shaping up to be an opportunity for increased work with pharmaceutical partners to explore expanded companion diagnostic indications for the increasingly established Guardant360.
"We believe that overcoming tissue limitations, together with a rapid turnaround time and broad commercial reach, is increasing interest in Guardant as a companion diagnostic partner," he said during the earnings call.
In this vein, the company announced this January that it is collaborating with Amgen to develop a novel CDx claim for Guardant360 for the pharma firm's investigational KRAS inhibitor, AMG 510, in non-small cell lung cancer.
"We believe that the development of Guardant360 CDx would ultimately increase the number of patients who are identified as eligible for [this drug] as a targeted therapy, thus improving access to this potentially life-changing treatment for the 13 percent of lung cancer patients with this biomarker, Talasaz said during the call.
Partnering for the development of novel drugs is also just one aspect of this picture.
FDA approval for Guardant360 is expected to mirror what the agency has concluded for analogous tissue-based comprehensive NGS assays, wherein a test panel may cover tens or hundreds of genes but regulatory approval is only furnished for those with FDA-recognized CDx indications.
This means that there could also be a process of CDx recognition for various other gene alterations or signatures that Guardant360 already measures, but which are not yet FDA recognized. One of these is tumor mutational burden, which is a target of significant interest across NGS test developers, both tissue- and blood-based.
Though Guardant has remained buttoned up on plans to seek regulatory approval for its TMB assessment as a companion to specific immunotherapy drugs, the company saw publication today of another study suggesting clinical utility in its ability to measure the biomarker, albeit using its broader research-use assay GuardantOMNI.
In a retrospective analysis led by researchers from the Perelman School of Medicine at the University of Pennsylvania and published Wednesday in Clinical Cancer Research, investigators found that patients in whom the GuardantOMNI assay detected higher volumes of mutations were more likely to see a clinical benefit from treatment with pembrolizumab (Merck's Keytruda) at six months. They were also more likely to survive longer without disease progression.
"There is an important clinical need to identify new, non-invasive biomarkers to help us guide each patient to the treatments that have the best chance of success for them, and our findings show we may now have a tool to help us do that," the study’s lead author Charu Aggarwal, an assistant professor at Penn, said in a statement.
Overall, the group analyzed 52 patients who received the immunotherapy as standard-of-care first-line treatment. TMB was significantly higher for patients who experienced a durable clinical benefit (a complete response, a partial response, or stable disease for more than six months) compared to those who did not.
Patients who achieved a DCB had a median of 21.3 mutations per megabase, compared to 12.4 per in those who did not.
Looking at progression-free and overall survival, the team found that a different TMB cutoff seemed to best differentiate responders from non-responders. The 28 patients with more than 16 detectable mutations per megabase had a median PFS of 14.1 months compared to 4.7 months for those with 16 or fewer.
Although the authors said the results need to be replicated in a larger prospective trial to be able to inform clinical practice, they wrote that theirs is the most comprehensive data so far showing a correlation between blood-based TMB and clinical outcomes in this first-line NSCLC immunotherapy setting.