Merus Presents Interim Data on MCLA-145 Monotherapy and in Combination with Pembrolizumab at the 2024 ASCO® Annual Meeting
Merus presented interim clinical data on MCLA-145 at the 2024 ASCO Annual Meeting. MCLA-145, a bispecific antibody targeting CD137 and PD-L1, was tested as monotherapy and in combination with pembrolizumab in patients with advanced or metastatic solid tumors. Key findings include a manageable safety profile and early clinical activity in difficult-to-treat cancers. Specifically, 5 partial responses were observed in monotherapy patients across various cancer types and 2 out of 6 patients at the recommended dose showed partial responses. In combination therapy, 1 partial response and 1 complete response were observed. MCLA-145 treatments showed reduced Grade ≥3 adverse events with less frequent dosing schedules. The company plans to advance clinical development of MCLA-145 potentially through collaboration.
- MCLA-145 showed early clinical activity in difficult-to-treat cancers.
- Manageable safety profile reported for both monotherapy and combination therapy.
- 5 partial responses observed in monotherapy across various cancer types.
- Reduced Grade ≥3 adverse events by 50% when shifting to Q3W dosing.
- Combination therapy observed 1 partial response and 1 complete response.
- Liver toxicity, a common CD137 related adverse event, was controlled with no Grade 4 events at Q3W.
- All patients were heavily pre-treated, with a median of 3 prior therapies, potentially impacting the generalizability of results.
- Only 5 partial responses observed in a small sample size of 52 monotherapy patients.
- Combination therapy showed efficacy with only 1 partial and 1 complete response out of 19 evaluable patients.
- The data is interim, and long-term efficacy and safety remain uncertain.
Insights
The interim data presented by Merus for MCLA-145, both as monotherapy and in combination with pembrolizumab, offers important insights into its clinical potential. The observation of partial responses in various cancer types, including glioblastoma and sarcoma, indicates that MCLA-145 may possess broad-spectrum activity against tumors that have been challenging to treat. The fact that one patient with glioblastoma experienced a response lasting over three years is particularly noteworthy, given the aggressive nature of this cancer.
Furthermore, the manageable safety profile, especially the reduction of high-grade treatment-emergent adverse events from a bi-weekly to a tri-weekly dosing schedule, suggests that MCLA-145 could be a viable option for long-term therapy. The control of liver toxicity, a known issue with CD137 targeting therapies, also supports this notion.
For retail investors, it's essential to note that while early results are promising, these findings are still in the preliminary phase. Successful outcomes in larger, more diverse patient populations will be necessary to gauge the full potential of MCLA-145. The combined therapy with pembrolizumab showing complete response in PD-L1+ NSCLC patients points toward a synergistic effect, which could be a game-changer in immunotherapy.
From a financial perspective, the interim data on MCLA-145 is encouraging for Merus. Positive clinical outcomes can significantly impact a company's valuation, especially in the biotech sector where successful therapies can lead to exponential growth. The combination therapy with pembrolizumab, a well-established checkpoint inhibitor, could potentially open new revenue streams through collaborative agreements and co-marketing opportunities.
Importantly, the shift to a tri-weekly dosing schedule not only improves the safety profile but also enhances patient compliance and reduces treatment costs, which are critical factors for market adoption. However, investors should be cautious and consider the typical high volatility associated with clinical-stage biotech companies. The results, while positive, are still interim and the final outcomes of ongoing and future trials will be more indicative of the drug's market potential.
Merus's focus on advancing petosemtamab into phase 3 trials and potential collaborations for MCLA-145 could further streamline operations and optimize resource allocation. This strategic focus may reassure investors about the company’s long-term vision and operational efficiency.
UTRECHT, The Netherlands and CAMBRIDGE, Mass., June 02, 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 updated interim clinical data on MCLA-145 monotherapy and in combination with pembrolizumab were presented at the 2024 American Society of Clinical Oncology® (ASCO®) Annual Meeting taking place in Chicago May 31-June 4, 2024.
“MCLA-145 as monotherapy or with pembrolizumab appears to have a manageable safety profile and early clinical activity in these difficult to treat cancers. Our biomarker data suggest that both dose and less frequent administration may be important determinants of clinical activity, and we are encouraged by the progress we are making with MCLA-145,” said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. “As our company is now increasingly focused on our lead asset petosemtamab and plan to initiate phase 3 trials in head and neck cancer later this year, we aim to advance clinical development of MCLA-145 in the context of a potential collaboration.”
MCLA-145 (CD137 x PD-L1 Biclonics®): Solid Tumors
Interim data included in the presentation describe data from patients (pts) with advanced/metastatic solid tumors who received MCLA-145 Q2W in 28 day cycles or every three weeks (Q3W) in 21 day cycles. Pts treated with the combination of MCLA-145 and pembrolizumab had cancers that either relapsed after PD-(L)1 therapies or were immunotherapy (IO) naïve.
Rapid oral presentation title: Phase I study of MCLA-145, a bispecific antibody targeting CD137 and PD-L1, in solid tumors, as monotherapy or in combination with pembrolizumab
Observations in the presentation include:
- As of a January 3, 2024 data cutoff date, 72 pts with multiple cancer types were treated;
25% of pts had non-small cell lung cancer (NSCLC)- All patients were heavily pre-treated with a median of 3 prior therapies; prior IO in
49% of the monotherapy pts and100% of the combination pts
- All patients were heavily pre-treated with a median of 3 prior therapies; prior IO in
- In monotherapy, 52 pts with a variety of tumor types and treated at different dose levels were evaluable for response
- 5 partial responses (PRs) were observed at different dose levels in glioblastoma (ongoing as of the cutoff date for >3 years), sarcoma (pretreated with pazopanib and gemcitabine/docetaxel), cervical, anal, and gastric cancer by Response Evaluation Criteria in Solid Tumors v1.1. per investigator assessment
- 2 of 6 pts PRs (
33% ) were observed for pts treated at the recommended dose for expansion (RDE), 40 mg Q3W - 3 of 6 PRs (
50% ) were observed for pts with evaluable baseline tumor CD8 T-cell density of ≥ 250 cells/mm2 responded
- In combination with pembrolizumab, 19 pts with a variety of tumor types and treated at different dose levels were evaluable for response
- 1 PR in Merkel cell carcinoma was observed at 25 mg Q3W
- 1 complete response was observed in PD-L1+ NSCLC at the RDE 40 mg Q3W
- 3 pts were continuing combination therapy at cutoff date
- MCLA-145 monotherapy or in combination with pembrolizumab had a well-tolerated and manageable safety profile at the RDE, 40mg Q3W
- Shifting from Q2W to Q3W resulted in a
50% reduction of Grade (G) ≥3 treatment-emergent adverse events in both monotherapy and combination therapy - Liver toxicity, a common CD137 related adverse event, was controlled with no G4 events observed at Q3W
- Shifting from Q2W to Q3W resulted in a
The full presentation is available on the Merus website.
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-145, 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®; our belief that for MCLA-145, biomarker data suggest that both dose and less frequent administration may be important determinants of clinical activity; our statements concerning the progress we are making with MCLA-145; our increasingly focus on our lead asset petosemtamab and plan to initiate phase 3 trials in head and neck cancer later this year; and our aim to advance clinical development of MCLA-145 in the context of a potential collaboration. 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
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