On May 26, 2022 Inspirna, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and biologic cancer therapeutics, reported new data from the ongoing Phase 1b clinical trial studying RGX-202-01 in combination with FOLFIRI and bevacizumab (FOLFIRI/BEV) in second-line advanced colorectal cancer (CRC) at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held June 3-7 in Chicago, Illinois (Press release, Inspirna, MAY 26, 2022, View Source [SID1234615133]).

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"These exciting new data show the potential of RGX-202-01 to drive meaningful responses in patients with advanced or metastatic colorectal cancer, especially in the KRAS mutant setting where there is a clear opportunity to improve on the standard of care," said Andrew Hendifar, M.D., Assistant Professor at Cedars-Sinai Medical Center and principal investigator on the study. "RGX-202-01 employs a novel mechanism by inhibiting SLC6a8, part of a pathway that becomes activated by colorectal cancer cells in order for these cells to survive, proliferate, and metastasize. Importantly, along with its preliminary signal of efficacy, these results also demonstrate that RGX-202-01 is very well-tolerated, enabling it to be combined with FOLFIRI/BEV and provide further optionality in this difficult-to-treat indication."

RGX-202-01 is an oral, potential first-in-class small molecule inhibitor of SLC6a8, a creatine transporter that drives colorectal cancer and certain other cancers’ progression. It is currently being evaluated in a Phase 1b dose escalation and expansion study in combination with FOLFIRI/BEV in second-line, advanced or metastatic CRC. The primary endpoint of the study is to determine maximum tolerated dose (MTD), overall response rate (ORR), and treatment-emergent adverse events (TEAEs). In the dose escalation stage of the study, two dose levels of RGX-202-01 with FOLFIRI/BEV have been evaluated in patients with advanced or metastatic CRC who have progressed on available oxaliplatin based first line therapy. In the ongoing expansion stage, additional patients with CRC are being treated at the dose of 3000mg PO BID to provide further characterization of the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the treatment.

Key findings to be presented at ASCO (Free ASCO Whitepaper) 2022:

The data cutoff for the presentation is April 28, 2022. As of data cutoff, 19 patients were enrolled in the study, including eight total patients in the dose escalation stage treated with either 2400mg twice daily (BID) of RGX-202-01 plus FOLFIRI/BEV (n = 4) or 3000mg BID RGX-202-01 plus FOLFIRI/BEV (n = 4), and 11 patients treated in the expansion stage with 3000mg BID RGX-202-01 plus FOLFIRI/BEV.
The dose escalation stage did not reach an MTD.
No dose limiting toxicities (DLT) were observed at either 2400mg BID or 3000mg BID doses.
There were only two Grade 4 TEAEs, and one of those was considered unrelated to treatment with RGX-202-01, and no Grade 5 TEAEs were observed.
17 patients were evaluable for response per RECIST v1.1 at data cutoff, of which 10 patients had KRAS mutant tumors and seven patients had KRAS wild-type tumors.
In the KRAS mutant population, five patients (50%) had confirmed partial responses (PR) and five patients (50%) had stable disease (SD).
In the KRAS wild-type population, one patient (14%) had an unconfirmed PR, five patients (71%) had SD, and one patient (14%) had progressive disease (PD).
Preliminary median progression-free survival (mPFS) was 11.8 months in the enrolled patients with KRAS mutant tumors.
Tumor regression was observed to deepen over time in patients with KRAS mutant tumors, with first radiographic achievement of PR appearing as late as 40 weeks post-treatment induction.
Overall, results show ORR and mPFS exceed expected benefit with standard-of-care alone in second-line CRC.
"We are very encouraged by the data reported today showing a strong signal of activity and meaningful responses, especially in patients harboring KRAS mutant tumors," said Masoud Tavazoie, M.D., Ph.D., Chief Executive Officer of Inspirna. "The results not only support our efforts to continue advancing RGX-202-01 in CRC, but also validate the ability of our RNA-DRIVEr platform to discover and develop new drug candidates with the potential to address cancers of high unmet medical need. We look forward to sharing these results at ASCO (Free ASCO Whitepaper) and further advancing RGX-202-01 drug development."

The abstract is available for viewing on the ASCO (Free ASCO Whitepaper) website, and the poster will be available at View Source following the session.

Poster Presentation Details

Title: Phase 1b study of RGX-202-01, a first-in-class oral inhibitor of the SLC6A8/CKB pathway, in combination with FOLFIRI and bevacizumab (BEV) in second-line advanced colorectal cancer (CRC)

Date and time: Saturday, June 4, 2022, 8:00 a.m. CDT

Session: Gastrointestinal Cancer—Colorectal and Anal

Abstract ID: 3579