Merus’ MCLA-129 Demonstrates Promising Single-Agent Efficiency in METex14 NSCLC in Poster Presentation at the 2024 ASCO® Annual Meeting

Rhea-AI Summary

Merus N.V. (Nasdaq: MRUS) announced promising results for its bispecific antibody MCLA-129 in treating METex14 non-small-cell lung cancer (NSCLC) at the 2024 ASCO Annual Meeting. The study involved 22 patients, with 64% continuing treatment as of February 16, 2024. MCLA-129 showed a 53% confirmed partial response rate and an 80% reduction in tumor size in evaluable patients. The safety profile included infusion-related reactions in 86% of patients, with serious reactions in 18%. The company plans to start a new cohort investigation combining MCLA-129 with chemotherapy later this year.

Positive

• 53% confirmed partial response rate in evaluable patients.
• 80% reduction in target lesion tumor size from baseline.
• 64% of patients continuing treatment as of the cutoff date.
• Plans to start a cohort investigating MCLA-129 in combination with chemotherapy.
• Potential for further development through partnership.

Negative

• 7 patients were excluded from the efficacy population.
• 4 patients discontinued due to adverse events before completing 2 treatment cycles.
• Infusion-related reactions occurred in 86% of patients, with 18% experiencing Grade 3 or higher reactions.
• A patient developed treatment-related interstitial lung disease.
• Venous thromboembolism was recorded in 2 patients, with 1 case possibly treatment-related.

Insights

Oncology Doctor

Understanding the efficacy of MCLA-129: The data presented indicates a notable response rate in patients with METex14 NSCLC. With 53% of patients showing confirmed partial responses, this bispecific antibody demonstrates solid potential. The differentiation between TKI-naïve and previously treated cancers is a critical detail; TKI-naïve patients responded better (60%) compared to those who had prior MET TKI treatment (43%). This suggests that MCLA-129 might be more effective as an earlier line of therapy.

Safety profile considerations: The safety data revealed a high incidence of infusion-related reactions (86% of patients), with 18% experiencing severe (>G3) reactions. This is a considerable safety signal that requires attention. The occurrence of treatment-related interstitial lung disease and venous thromboembolism also flags significant adverse events that need to be carefully managed in a clinical setting.

Implications for further development: The ongoing response and adverse event rates underscore the need for a careful balance between efficacy and safety. Combining MCLA-129 with chemotherapy in 2L+ EGFRm NSCLC, as planned, may enhance therapeutic outcomes but could also introduce compounded risks. Close monitoring and strategic patient selection will be imperative.

Medical Research Analyst

Clinical trial metrics: The trial had a relatively small sample size (22 patients), which limits the generalizability of the findings. While the response rate of 53% for partial responses is promising, the small cohort and short observation period might mean these results don't fully represent long-term outcomes or rare adverse effects. It's essential to confirm these results in larger, more diverse populations.

Strategic alignment: The potential partnership opportunities mentioned by the CEO highlight a strategic angle for investors. Successful partnerships can bring in additional resources and expertise, important for advancing MCLA-129 through later-stage trials and eventual commercialization. Investors should monitor announcements regarding such collaborations closely.

Market impact: The collaboration with Betta Pharmaceuticals, which holds exclusive rights in China, is a significant strategic move. This collaboration could accelerate product development in one of the fastest-growing markets for oncology drugs, potentially leading to quicker revenue realization from that region.

UTRECHT, The Netherlands and CAMBRIDGE, Mass., June 03, 2024 (GLOBE NEWSWIRE) -- Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics^® and Triclonics^®), today announced the publication of a poster regarding MCLA-129 presented at the 2024 American Society of Clinical Oncology^® (ASCO^®) Annual Meeting taking place in Chicago May 31-June 4, 2024.

“These data continue to support our view that MCLA-129 is a very active drug, and that our Biclonics^® platform really can create clinically active drugs for patients with cancer. We plan to start a cohort investigating MCLA-129 in combination with chemotherapy in 2L+ EGFRm NSCLC later this year,” said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. “We continue to evaluate MCLA-129 with a focused investment and remain interested in a partnership to resource the further development of this asset.”

Poster presentation title: Efficacy and safety of MCLA-129, an anti-EGFR/c-MET bispecific antibody, in non-small-cell lung cancer (NSCLC) with Hepatocyte Growth Factor Receptor (c-MET) exon 14 skipping mutations (METex14)

Observations in the presentation include:

• As of a February 16, 2024 data cutoff date, 22 patients (pts) were treated and 14 pts (64%) were continuing treatment
  • All the pts received MCLA-129 in monotherapy at the dose of 1500 mg, every 2 weeks
  • Pts received a median of 2 lines of prior therapy
  • 10 pts (45%) were tyrosine kinase inhibitor (TKI)-naïve and 12 (55%) had received prior TKIs
  • 7 pts were excluded from the efficacy population. 4 discontinued due to AEs <2 cycles of treatment and did not experience progressive disease while on study; 3 were ongoing as of the cutoff date with <2 treatment cycles
• 15 pts were evaluable for response having received ≥2 treatment cycles, measurable disease at baseline and ≥1 post-baseline scan
  • Response rate overall: 3 partial responses (PRs) and 6 unconfirmed PRs (uPRs) were observed by Response Evaluation Criteria in Solid Tumors v1.1 per investigator assessment; 5 of the 6 uPRs were confirmed and 1 uPR progressed after the data cutoff (8/15 confirmed PRs [53%])
  • 6 of 8 TKI-naïve cancers responded, one of which was an initial uPR that progressed after data cutoff
  • 3 of 7 cancers with prior MET TKI responded
  • Reduction in target lesion tumor size from baseline was demonstrated in 12 pts (80%)
• Early safety assessment in 22 pts treated with MCLA-129 monotherapy included
  • Infusion related reactions (composite term) in 86% (18% ≥ Grade (G)3)
  • One pt had treatment-related interstitial lung disease (G2)
  • Venous thromboembolism was recorded in 2 pts (1 G3 possibly treatment-related, the other G2 and not related to treatment)

The full presentation is available on the Publications page of our website. 

MCLA-129 is subject to a collaboration and license agreement with Betta Pharmaceuticals Co. Ltd. (Betta), which permits Betta to develop MCLA-129 and potentially commercialize exclusively in China, while Merus retains global rights outside of China. An abstract sponsored by Betta entitled: Efficacy and safety of MCLA-129, an EGFR/c-MET bispecific antibody, in advanced non-small cell lung cancer (NSCLC) was accepted for poster presentation at 2024 ASCO^®.

About Merus
Merus is a clinical-stage oncology company developing innovative full-length human bispecific and trispecific antibody therapeutics, referred to as Multiclonics^®. Multiclonics^® are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. For additional information, please visit Merus’ website, X and LinkedIn.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the clinical development of our clinical candidates, including MCLA-129, future clinical trial results or interim data, clinical activity and safety profile, and development plans in the on-going trials and described in forthcoming posters or presentations; the ability of our Mutliclonics^® platforms; our belief that these data continue to support our view that MCLA-129 is a very active drug for patients with cancer; our plans to start a cohort investigating MCLA-129 in combination with chemotherapy in 2L+ EGFR mutant NSCLC in 2024; and our continued evaluation MCLA-129 with a focused investment and interest in a partnership to resource the further development of this asset. These forward-looking statements are based on management’s current expectations. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our need for additional funding, which may not be available and which may require us to restrict our operations or require us to relinquish rights to our technologies or Biclonics®, Triclonics^® and multispecific antibody candidates; potential delays in regulatory approval, which would impact our ability to commercialize our product candidates and affect our ability to generate revenue; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; the unpredictable nature of our early stage development efforts for marketable drugs; potential delays in enrollment of patients, which could affect the receipt of necessary regulatory approvals; our reliance on third parties to conduct our clinical trials and the potential for those third parties to not perform satisfactorily; impacts of the market volatility; we may not identify suitable Biclonics^® or bispecific antibody candidates under our collaborations or our collaborators may fail to perform adequately under our collaborations; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; protection of our proprietary technology; our patents may be found invalid, unenforceable, circumvented by competitors and our patent applications may be found not to comply with the rules and regulations of patentability; we may fail to prevail in potential lawsuits for infringement of third-party intellectual property; and our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks.

These and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-Q for the quarter ended March 31, 2024 filed with the Securities and Exchange Commission, or SEC, on May 8, 2024, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except as required under applicable law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.

Multiclonics^®, Biclonics^® and Triclonics^® are registered trademarks of Merus N.V. 

FAQ

What were the results of Merus' MCLA-129 study in METex14 NSCLC presented at the 2024 ASCO Annual Meeting?

The study showed a 53% confirmed partial response rate and an 80% reduction in tumor size among evaluable patients.

How many patients were treated with MCLA-129 in Merus' recent study?

22 patients were treated with MCLA-129, with 64% continuing treatment as of the February 16, 2024, cutoff date.

What adverse events were observed in the MCLA-129 study?

Infusion-related reactions occurred in 86% of patients, with 18% experiencing Grade 3 or higher reactions. Additionally, one patient developed treatment-related interstitial lung disease, and two patients experienced venous thromboembolism.

What future plans does Merus have for MCLA-129?

Merus plans to start a cohort investigating MCLA-129 in combination with chemotherapy for 2L+ EGFRm NSCLC later this year and is interested in partnerships for further development.

What percentage of patients showed a reduction in tumor size in the MCLA-129 study?

80% of patients demonstrated a reduction in target lesion tumor size from baseline.