Syndax Announces Plans to Advance into Phase 1b Portion of Trial Evaluating Revumenib in Relapsed or Refractory Metastatic MSS CRC

Rhea-AI Summary

Syndax Pharmaceuticals announced the advancement into Phase 1b of its Phase 1/2 trial of revumenib for relapsed or refractory metastatic MSS colorectal cancer (CRC). This decision follows a favorable safety profile observed in Phase 1a, as reviewed by the Independent Data Monitoring Committee (IDMC). In Phase 1a, 19 patients were treated across three dose levels, with revumenib being well-tolerated and no Grade 3 or higher treatment-related adverse events reported. Preliminary efficacy showed that 33% of patients had stable disease at 16 weeks. The trial will proceed with a 276 mg TID dosage in Phase 1b.

Positive

• Advancement into Phase 1b after favorable safety profile in Phase 1a.
• No Grade 3 or higher treatment-related adverse events observed.
• 33% of patients had stable disease at 16 weeks.
• Revumenib was well-tolerated at all dose levels.
• Supporting efficacy signals observed with a 33% stable disease rate.

Negative

• Only 44% of patients showed stable disease at 8 weeks, indicating room for improvement.
• The trial has data with only 19 patients in Phase 1a.

Oncology Doctor

Revumenib's progression to Phase 1b in treating relapsed or refractory metastatic microsatellite stable colorectal cancer (MSS CRC) is a significant step forward in oncology. Revumenib is a menin inhibitor, which is a novel therapeutic approach targeting a specific protein involved in cancer growth. The positive safety profile observed in Phase 1a, with no severe treatment-related adverse events, is particularly promising. This positions Revumenib as a potentially safer alternative compared to existing treatments.

The 33% stable disease rate at 16 weeks observed in the trial is a substantial finding. For context, achieving stable disease in heavily pre-treated patients indicates that the drug is effectively halting disease progression, which is a critical outcome in cancer treatment. This result, combined with the drug's favorable safety profile, suggests that Revumenib could fill an unmet need in MSS CRC, where treatment options are currently limited.

Short-term implications: Investors should note that the advancement to Phase 1b means Syndax is confident in the drug's potential efficacy and safety. However, it's essential to recognize that the drug is still in the early stages of clinical development and further trials are necessary to confirm these findings.

Long-term implications: If future trials continue to show positive results, Revumenib could become a cornerstone treatment for MSS CRC, potentially leading to significant market adoption and revenue growth for Syndax. However, the drug's journey through clinical trials is fraught with uncertainties and investors should be cautious and monitor upcoming trial data closely.

Financial Analyst

The announcement marks a critical milestone for Syndax Pharmaceuticals as it progresses with Revumenib. From a financial perspective, this advancement implies potential future revenue streams if the drug continues to show promise through further stages of clinical trials. As a clinical-stage biopharmaceutical company, Syndax's valuation heavily relies on its pipeline progress and the market potential of its drugs.

Short-term analysis: The favorable safety profile and early efficacy signals can bolster investor confidence, potentially leading to a positive market response. However, the company's cash flow and financial health remain pivotal, as clinical trials are costly and Syndax must ensure it has adequate funding to continue its research and development activities.

Long-term analysis: Should Revumenib reach commercialization, it could significantly enhance Syndax's market position and financial performance. Considering the promising initial data, the drug could attract partnerships or acquisition interest, further boosting the company's financial prospects. Yet, investors must remain cautious of the high-risk nature of biopharmaceutical stocks, as any negative trial results could adversely impact Syndax's stock price and financial stability.

Medical Research Analyst

The data supporting Revumenib's continuation to Phase 1b for MSS CRC is noteworthy in the medical research community. The use of menin inhibitors is still relatively novel and Revumenib's promising initial safety and efficacy profile could pave the way for new therapeutic paradigms in colorectal cancer treatment. The trial's results should be interpreted with cautious optimism, as further validation in larger cohorts is required.

Trial design insights: The Phase 1a trial's ability to test multiple dose levels and observe no Grade 3 or greater treatment-related adverse events is commendable. Selecting 276 mg TID as the go-forward dose indicates a balance between efficacy and manageable side effects. The absence of severe adverse events and the reported rates of stable disease are critical in early-phase trials, laying the groundwork for more comprehensive future studies.

Implications for future research: This trial's outcomes might encourage more research into menin inhibitors for solid tumors beyond hematological malignancies. The focus will likely shift towards understanding the molecular mechanisms that underlie the observed efficacy and further refining patient selection criteria to enhance treatment outcomes.

– IDMC recommendation to advance based on favorable safety profile observed in Phase 1a portion of trial –

WALTHAM, Mass., June 6, 2024 /PRNewswire/ -- Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, today announced that it has advanced into the Phase 1b portion of its Phase 1/2 proof-of-concept trial of revumenib, the Company's highly selective, oral menin inhibitor, as a monotherapy in patients with relapsed or refractory (R/R) metastatic microsatellite stable (MSS) colorectal cancer (CRC). The Company's decision was supported by the trial's Independent Data Monitoring Committee (IDMC) following its recent pre-planned review of initial data from the Phase 1a portion of the trial.

"In our first clinical trial exploring expansion of revumenib beyond hematological malignancies, initial results from the Phase 1a portion of the trial are encouraging," said Neil Gallagher, M.D., Ph.D., President, Head of Research and Development at Syndax. "We are particularly pleased to observe a compelling safety profile consistent with our existing revumenib dataset, as well as efficacy signals that include a 33% stable disease rate at 16 weeks as a monotherapy, which compares favorably with current standard-of-care and supports advancement into the Phase 1b portion. As we continue to focus on preparations for the potential launches of revumenib and axatilimab later this year, we look forward to continuing to explore the role revumenib could play in the treatment of R/R metastatic MSS CRC."

The Phase 1/2 trial (NCT05731947) is designed to assess the safety, tolerability, and anti-tumor activity of revumenib in patients with relapsed or refractory metastatic MSS CRC. The Phase 1a dose escalation portion of the trial enrolled a total of 19 patients who had a median of four prior therapies across three dose cohorts, including 163 mg, 226 mg, and 276 mg three times a day (TID).  Revumenib was well-tolerated at all dose levels tested and the safety profile was consistent with the Company's previously reported data. No Grade 3 or greater treatment-related adverse events (TRAEs) were observed and the most common TRAEs were decreased appetite, dysgeusia, nausea, and fatigue.  In addition, the initial efficacy results provide early clinical support that revumenib may be able to impact disease progression in R/R patients with metastatic MSS CRC. At doses believed to achieve full target saturation, dose levels 2 and 3, 44% (4/9) of patients had stable disease at 8 weeks, and 33% (3/9) of patients had stable disease at 16 weeks.  One patient with prolonged stable disease remained on study for 32 weeks. Based on the initial data, 276 mg TID was selected as the go-forward dose in the Phase 1b portion.

About Metastatic MSS CRC

Metastatic microsatellite stable (MSS) colorectal cancer (CRC) represents the second leading cause of cancer death in the U.S. with an estimated incidence in the relapsed or refractory (R/R) setting of over 55,000 patients per year. Activation of the Wnt/β-catenin signaling pathway is believed to be a key initiating step and growth driver for the majority of CRC tumors. The menin-MLL1 protein complex has been shown to regulate β-catenin activity and disrupting this complex through menin inhibition blocks growth of Wnt/β-catenin driven CRC tumors in preclinical models.

About Revumenib

Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged (KMT2Ar), also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and mutant nucleophosmin (mNPM1) acute myeloid leukemia (AML). Positive topline results from the pivotal AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology Annual Meeting, and data from the Phase 1 portion of AUGMENT-101 in acute leukemia was published in Nature. Pivotal data from the AUGMENT-101 trial in R/R NPM1 AML patients are expected in the fourth quarter of 2024.  Revumenib was granted Orphan Drug Designation by the FDA and European Commission for the treatment of patients with AML and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.  The NDA filing for revumenib in R/R KMT2Ar acute leukemia is currently under Priority Review by the FDA under RTOR with a PDUFA action date of September 26, 2024.

About Syndax

Syndax Pharmaceuticals is a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies. Highlights of the Company's pipeline include revumenib, a highly selective menin inhibitor, and axatilimab, a monoclonal antibody that blocks the CSF-1 receptor. For more information, please visit www.syndax.com or follow the Company on X (formerly Twitter) and LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "anticipate," "believe," "could," "estimate," "expects," "intend," "may," "plan," "potential," "predict," "project," "should," "will," "would" or the negative or plural of those terms, and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Syndax's expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the progress, timing, clinical development and scope of clinical trials, the reporting of clinical data for Syndax's product candidates, and the potential use of its product candidates to treat various cancer indications and fibrotic diseases. Many factors may cause differences between current expectations and actual results, including: unexpected safety or efficacy data observed during preclinical or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; changes in expected or existing competition; changes in the regulatory environment; failure of Syndax's collaborators to support or advance collaborations or product candidates; and unexpected litigation or other disputes. Other factors that may cause Syndax's actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Syndax's filings with the U.S. Securities and Exchange Commission, including the "Risk Factors" sections contained therein. Except as required by law, Syndax assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

Syndax Contact
Sharon Klahre
Syndax Pharmaceuticals, Inc.
sklahre@syndax.com
Tel 781.684.9827

SNDX-G

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SOURCE Syndax Pharmaceuticals, Inc.

FAQ

What is the latest update on Syndax's trial for revumenib in metastatic MSS CRC?

Syndax has advanced into Phase 1b following favorable safety and preliminary efficacy results from Phase 1a.

What were the results of the Phase 1a trial for revumenib?

The Phase 1a trial showed that revumenib was well-tolerated with no Grade 3 or higher adverse events and a 33% stable disease rate at 16 weeks.

What dosage will be used in the Phase 1b trial for revumenib?

The Phase 1b trial will use a 276 mg TID dosage of revumenib.

How many patients were enrolled in the Phase 1a trial for revumenib?

A total of 19 patients were enrolled in the Phase 1a trial.

What is the significance of the Independent Data Monitoring Committee's recommendation for Syndax?

The IDMC recommended advancing to Phase 1b due to the favorable safety profile observed in Phase 1a.