Blueprint Medicines to Present the First Promising and Most Advanced Clinical Data for a CDK2 Inhibitor in Combination with an Approved CDK4/6 Inhibitor in HR+/HER2- Breast Cancer at the 2024 ASCO Annual Meeting
Blueprint Medicines announced updated Phase 1 data for their CDK2 inhibitor, BLU-222, in combination with ribociclib and fulvestrant, for HR+/HER2- breast cancer. The study showed BLU-222 was well-tolerated with no dose-limiting toxicities. Updated data indicate significant biomarker reductions correlated with BLU-222 exposure. Early results suggest clinical activity, including one unconfirmed partial response. Detailed findings will be presented at the 2024 ASCO Annual Meeting.
- BLU-222, in combination with ribociclib and fulvestrant, was well-tolerated at all tested dose levels.
- No dose-limiting toxicities or severe adverse events were reported.
- Significant biomarker reductions (TK1 and ctDNA) were observed, indicating potential clinical benefit.
- Early signal of clinical activity includes an unconfirmed partial response in a highly pretreated patient.
- Pharmacokinetic data showed dose-proportional exposures with sustained coverage above predicted efficacious concentration.
- The maximum tolerated dose of BLU-222 has not yet been identified.
- The clinical activity evidence remains early and unconfirmed.
- Patients had to have previously progressed on prior CDK4/6 inhibitors, indicating a challenging patient population.
Insights
The updated Phase 1 data from Blueprint Medicines suggests that their CDK2 inhibitor, BLU-222, in combination with ribociclib and fulvestrant, shows early promise in the treatment of HR+/HER2- breast cancer. The absence of dose-limiting toxicities and severe adverse events, as well as the reduction in biomarkers like thymidine kinase 1 (TK1) and circulating tumor DNA (ctDNA), are particularly noteworthy. These biomarkers are significant as they are indicators of tumor proliferation and burden, respectively. A potential unconfirmed partial response in a highly pre-treated patient is encouraging, although further data and validation are needed before drawing firm conclusions. Overall, this could represent a significant advancement in metastatic breast cancer treatment, but investors should temper expectations until more comprehensive data is available.
From a medical research perspective, the compelling reductions in TK1 and ctDNA biomarkers and the favorable pharmacokinetic profile of BLU-222 offer promising signals. The mechanism of action underlying CDK2 inhibitors could address resistance mechanisms in patients who have progressed on CDK4/6 inhibitors. However, it is important to recognize that these are early-phase results and the study is still in the dose escalation phase. The real impact will be seen in later-stage, larger-scale trials which will provide more robust efficacy and safety data. Investors should note that despite the positive early signals, the path from Phase 1 to market approval is fraught with challenges.
For retail investors, the news about Blueprint Medicines' BLU-222 in combination with ribociclib and fulvestrant is generally positive. The absence of dose-limiting toxicities and early evidence of clinical activity increase the likelihood of successful later-stage trials, which could potentially lead to FDA approval and subsequent market adoption. However, it's prudent to consider that this is a long-term play, as further clinical trials are needed. If successful, BLU-222 could provide a new revenue stream and strengthen Blueprint Medicines' portfolio, potentially leading to an increase in stock value. However, investors should remain cautious and aware of the inherent risks associated with clinical development.
-- Updated Phase 1 dose escalation data show that BLU-222 in combination with ribociclib and fulvestrant was well-tolerated at clinically active dose levels with no dose-limiting toxicities --
-- Early signal of clinical activity includes compelling biomarker reductions correlated with BLU-222 exposure --
"At ASCO, we will present highly encouraging clinical data showing that our selective CDK2 inhibitor BLU-222, in combination with ribociclib, a standard of care CDK4/6 inhibitor for HR+ breast cancer, is very well-tolerated and delivers early evidence of clinical activity. This represents a highly significant milestone and holds promise as an important new cornerstone for the treatment of breast cancer, including in the front-line metastatic setting," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "These data validate the potency and selectivity of BLU-222, its potential as a first- and best-in-class CDK2 inhibitor, and its use as the combination partner of choice in breast cancer. With these data in hand, we are advancing ongoing partnering discussions that aim to accelerate development of BLU-222 into registration-directed clinical trials."
Updated Phase 1/2 VELA Trial Results
Based on previously reported positive BLU-222 monotherapy clinical data, a combination dose escalation arm was initiated in the VELA trial to assess the safety and clinical activity of BLU-222 in combination with ribociclib, a CDK4/6 inhibitor approved by the
The combination of BLU-222, ribociclib, and fulvestrant was well-tolerated at all BLU-222 dose levels tested. No dose-limiting toxicities, treatment-related severe adverse events (SAEs), or BLU-222-related treatment discontinuations were reported. Treatment-related hematologic and gastrointestinal AEs were generally mild. The maximum tolerated combination dose has not been identified, and combination dose escalation is ongoing.
Pharmacokinetic data showed dose-proportional exposures of BLU-222, with sustained coverage above the predicted efficacious concentration at the 400 mg BID dose level. In addition, the combination of BLU-222 with ribociclib and fulvestrant had no clinically meaningful impact on individual drug exposures.
Preliminary clinical activity showed compelling reductions in thymidine kinase 1 (TK1) and circulating tumor DNA (ctDNA), biomarkers that have been shown to be predictive of clinical benefit. TK1, a biomarker of tumor proliferation, had the deepest reduction among patients treated with BLU-222 400 mg BID, ribociclib 400 mg QD, and combined with fulvestrant, and was statistically significantly correlated with BLU-222 exposure. All patients with evaluable ctDNA, a biomarker of tumor burden, treated with the BLU-222 400 mg BID combination dose regimen showed ctDNA reductions. Early evidence of clinical benefit includes an unconfirmed partial response in a patient who had previously progressed following six lines of therapy in the metastatic setting, including prior palbociclib and trastuzumab deruxtecan. These data highlight the impact of CDK2 inhibition when BLU-222 is combined with other therapies.
Detailed data will be presented by Dr. Dejan Duric from the Henri and Belinda Termeer Center for Targeted Therapies at Massachusetts General Hospital on June 2, 2024, during the "Breast Cancer – Metastatic" poster session at 9:00 a.m. CT. At the time of presentation, a copy of the poster will be available in the "Science—Publications and Presentations" section of the company's website at www.BlueprintMedicines.com.
About BLU-222
BLU-222 is a highly selective and potent investigational CDK2 inhibitor with first- and best-in-class potential, designed by scientists at Blueprint Medicines. CDK2 is a cell cycle regulator and an important cancer target, with relevance in HR+/HER2- breast cancer and other malignancies, such as subsets of ovarian and endometrial cancer. Across multiple cancer types, aberrant CCNE1 hyperactivates CDK2, resulting in cell cycle dysregulation and tumor proliferation. Aberrant CCNE1 has been observed as a primary driver of disease, as well as a mechanism of resistance to CDK4/6 inhibitors. In HR+/HER2- breast cancer, the advent of CDK4/6 inhibitors has improved treatment; however, disease progression is nearly universal, and new innovation is needed to improve outcomes and prolong clinical benefit. Historically, CDK2 inhibitor development by others has been challenged due to poor selectivity limiting tolerability and combination potential. Beyond BLU-222, Blueprint Medicines is advancing additional preclinical therapeutic candidates for cell cycle targets including BLU-956, a next-generation CDK2 inhibitor, a CDK2 targeted protein degradation program, and an additional undisclosed research program.
About Blueprint Medicines
Blueprint Medicines is a global, fully integrated biopharmaceutical company that invents life-changing medicines. We seek to alleviate human suffering by solving important medical problems in two core focus areas: allergy/inflammation and oncology/hematology. Our approach begins by targeting the root causes of disease, using deep scientific knowledge in our core focus areas and drug discovery expertise across multiple therapeutic modalities. We have a track record of success with two approved medicines, including AYVAKIT®/AYVAKYT® (avapritinib) which we are bringing to patients with systemic mastocytosis (SM) in the
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation: statements regarding plans, strategies, timelines and expectations for Blueprint Medicines' operations, including its expectations for our current or future approved drugs and drug candidates, including BLU-222; the development of BLU-222 and whether it has first-and best-in-class potential; the potential benefits of any of our current or future approved drugs or drug candidates in treating patients, including the potential benefits of BLU-222 in combination with ribociclib and fulvestrant in patients with HR+/HER2- breast cancer; and the potential to partner with a third party to accelerate development of BLU-222 into registration-directed clinical trials. The words "aim," "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "target" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks and uncertainties related to: the delay of any current or planned clinical trials or the development of the company's current or future drug candidates; the company's ability to successfully demonstrate the safety and efficacy of its drug candidates and gain approval of its drug candidates on a timely basis, if at all; the possibility that preclinical and clinical results for the company's drug candidates may not support further development of such drug candidates either as monotherapies or in combination with other agents or may impact the anticipated timing of data or regulatory submissions; the timing of the initiation of clinical trials and trial cohorts at clinical trial sites and the possibility patient enrollment rates may be delayed or slower than anticipated; the actions of regulatory agencies and how this may affect the initiation, timing and progress of clinical trials; the company's ability to obtain, maintain and enforce patent and other intellectual property protection for its products and current or future drug candidates it is developing; and the success of the company's current and future collaborations, partnerships or licensing arrangements. Any forward-looking statements contained in this press release represent the company's views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, the company explicitly disclaims any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements.
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