On January 5, 2023 Inspirna, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule cancer therapeutics, reported interim data from its ongoing Phase 1b/2 clinical trial of abequolixron in patients with non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) (Press release, Inspirna, JAN 5, 2023, View Source [SID1234625898]).

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Abequolixron (RGX-104) is a first-in-class, small molecule liver X receptor (LXR) agonist designed to target APOE dysregulation and enhance anti-tumor immunity by inhibiting tumor angiogenesis, depleting myeloid derived suppressor cells (MDSC), and activating cytotoxic T lymphocytes (CTL). Abequolixron is currently being evaluated in a Phase 1b/2 clinical trial in combination with docetaxel in second- or third-line (2/3L) NSCLC as well as second-line (2L) SCLC. The primary objectives of the study include characterizing the safety profile and the antitumor activity of the abequolixron and docetaxel combination.

"The data thus far demonstrate that abequolixron is well tolerated in combination with full dose docetaxel, while showing encouraging clinical activity suggesting that this drug candidate could be a valuable addition to a current standard of care chemotherapy in heavily-pretreated patients with lung cancer," said Hossein Borghaei, D.O., M.S., Chief of the Division of Thoracic Medical Oncology at Fox Chase Cancer Center and Principal Investigator on the study. "I am very encouraged by the overall response rate, disease control rate, and time to progression so far seen in the study and I look forward to further evaluation of this unique compound as the clinical trial progresses."

"These data, while early, clearly show the potential that abequolixron may have in driving deep responses in patients with heavily-pretreated lung cancer," said Masoud Tavazoie, M.D., Ph.D., Chief Executive Officer of Inspirna. "We are excited to begin the new year by announcing these promising data for abequolixron and look forward to sharing more updates as we continue advancing our novel pipeline in difficult-to-treat cancers."

Key findings from the data

As of December 2, 2022, 17 patients were treated at the Recommended Phase 2 Dose (RP2D) as determined in the dose escalation stage, with 120mg abequolixron twice daily (BID), 5 days on/2 days off, plus docetaxel. Thirteen patients were evaluable for response per RECIST v1.1, including five patients with 2/3L NSCLC and eight patients with 2L SCLC.
The ORR across all evaluable patients was 38% (n=13), with a disease control rate (DCR) of 77%, including five patients who achieved partial response (PR).
In the 2/3L NSCLC cohort, of five evaluable patients, four patients achieved PRs with two patients achieving confirmed partial responses. Four of the five patients were on study treatment for > 19 weeks, including one patient for 25 weeks, one patient for 28 weeks and one ongoing patient at 37 weeks.
In the 2L SCLC cohort, of eight evaluable patients, one patient achieved a PR and five patients had a best overall response (BoR) of stable disease (SD). Four patients (50%) were on study drug progression free for > 24 weeks. One of the patients with a BoR of SD, although experiencing CNS progression at week 12, stayed on therapy for clinical benefit for 30 weeks without experiencing systemic PD.
Across the two cohorts (N=17), the most common TEAEs were fatigue in 12 patients, diarrhea and nausea in 9 patients, decreased appetite in 8 patients and neutropenia and weight loss in 7 patients. Of the most common TEAEs, Grade 4 events were neutropenia (2 patients) and Grade 3 events were fatigue (2 patients), diarrhea (1 patient), nausea (1 patient), decreased appetite (1 patient) and the others were Grade < 2.
The expansion stage of the study is ongoing and continues to enroll patients with 2/3L NSCLC. In addition, this Phase 1b/2 study includes an ongoing expansion arm of abequolixron in combination with Yervoy (ipilimumab) in second- or third-line endometrial cancer as part of a clinical collaboration with Bristol Myers Squibb.

About Abequolixron (RGX-104)

Abequolixron is an orally administered small molecule agonist of the Liver X Receptor (LXR) which activates expression of the APOE tumor suppressor protein. APOE expression becomes dysregulated (silenced) in the tumors of select patients with solid cancers. APOE dysregulation results in increased tumor angiogenesis (tumor blood vessel growth) as well as a shifting of the tumor myeloid cell population from immune-stimulatory to immune-suppressive, which are both counteracted by abequolixron. Abequolixron is currently being tested in a Phase 1b/2 clinical trial in combination with standard-of-care regimens in several lung cancer indications that are enriched for APOE dysregulation, including SCLC and NSCLC.