On January 17, 2025 AstraZeneca reported that Calquence (acalabrutinib) in combination with bendamustine and rituximab has been approved in the US for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (Press release, AstraZeneca, JAN 17, 2025, View Source [SID1234649766]).

The approval was granted by the Food and Drug Administration (FDA) after securing Priority Review. It was based on results from the ECHO Phase III trial which were presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Congress.

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL), often diagnosed at an advanced stage.[1],[2] It is estimated that there are more than 21,000 patients diagnosed with MCL in the US, UK, France, Germany, Spain, Italy, Japan and China.[3]

Michael Wang, MD, Puddin Clarke Endowed Professor, Director of Mantle Cell Lymphoma Program of Excellence and principal investigator in the trial, said: "Managing this aggressive cancer requires maximising efficacy while maintaining tolerability, especially for elderly patients. Results from the pivotal ECHO trial highlight the promise of the acalabrutinib combination in defining a new standard of care, with today’s approval underscoring the transformative potential of this regimen as a first-line treatment for older patients with mantle cell lymphoma."

Dave Fredrickson, Executive Vice-President, Oncology Haematology Business Unit, AstraZeneca, said: "With today’s approval, Calquence provides a critical new treatment option to mantle cell lymphoma patients in the US, with Calquence proven to deliver nearly one and a half years of additional time without disease progression. This approval brings a new and effective treatment option to those living with this disease and further reinforces our belief in Calquence as a backbone therapy across multiple blood cancers."

Meghan Gutierrez, Chief Executive Officer, Lymphoma Research Foundation, said: "New treatment options have long been needed in the first-line treatment of mantle cell lymphoma in the US. Patients with this rare and often aggressive cancer can experience severe symptoms by the time they are diagnosed – having an effective therapy that can significantly improve outcomes for patients early in the treatment process is a much-needed advancement."

Results from the ECHO trial showed Calquence plus bendamustine and rituximab reduced the risk of disease progression or death by 27% compared to standard-of-care chemoimmunotherapy (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.57-0.94; p=0.016). Median PFS was 66.4 months for patients treated with the Calquence combination versus 49.6 months with chemoimmunotherapy alone.

This approval additionally converts Calquence’s accelerated approval to a full approval for adult patients with MCL treated with at least one prior therapy, as granted by the FDA in October 2017.

The ECHO trial enrolled patients throughout the COVID-19 pandemic. After censoring for COVID-19 deaths, PFS was further improved in both arms, with the Calquence combination reducing the risk of disease progression or death by 36% (HR 0.64; 95% CI 0.48-0.84). Although OS data were not mature at the time of the analysis, when censored for COVID-19, a favourable trend was seen for OS (HR 0.75; 95% CI 0.53-1.04), despite 69% of patients in the chemoimmunotherapy arm receiving treatment with a BTK inhibitor on relapse or disease progression.

The safety and tolerability of Calquence was consistent with its known safety profile, and no new safety signals were identified.

The US regulatory submission was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, Calquence plus chemoimmunotherapy is also under review by regulatory authorities in Australia, Canada, and Switzerland for the same indication. Regulatory applications are also under review in the EU, Japan, and other countries based on the ECHO results.

Notes

Mantle cell lymphoma (MCL)
While MCL patients initially respond to treatment, patients do tend to relapse.[4] MCL comprises about 3-6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 population in Western countries; in the US, it is estimated that approximately 4,000 new patients are diagnosed with MCL each year.4,[5]

ECHO
ECHO is a randomised, double-blind, placebo-controlled, multi-centre Phase III trial evaluating the efficacy and safety of Calquence plus bendamustine and rituximab compared to SoC chemoimmunotherapy (bendamustine and rituximab) in adult patients at or over 65 years of age (n=635) with previously untreated MCL.[6] Patients were randomised 1:1 to receive either Calquence or placebo administered orally twice per day, continuously, until disease progression or unacceptable toxicity. Additionally, all patients received six 28-day cycles of bendamustine on days 1 and 2 and rituximab on day 1 of each cycle, followed by rituximab maintenance for two years if patients achieved a response after induction therapy.6

The primary endpoint is PFS assessed by an Independent Review Committee; other efficacy endpoints include OS, overall response rate (ORR), duration of response (DoR) and time to response (TTR).6 The trial was conducted in 27 countries across North and South America, Europe, Asia and Oceania.6

The ECHO trial enrolled patients from May 2017 to March 2023, continuing through the COVID-19 pandemic. Prespecified PFS and OS analyses censoring for COVID-19 deaths were conducted to assess the impact of COVID-19 on the study outcome in alignment with the FDA. Patients with blood cancer remain at a disproportionately high risk of severe outcomes from COVID-19, including hospitalisation and death compared to the general population.6,[7]

Calquence
Calquence (acalabrutinib) is a second-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.[8] In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.

Calquence has been used to treat more than 85,000 patients worldwide[9] and is approved for the treatment of chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) in the US and Japan, approved for CLL in the EU and many other countries worldwide and approved in China for relapsed or refractory CLL and SLL. Calquence is also approved for the treatment of adult patients with previously untreated MCL in the US, and in China and several other countries for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Calquence is not currently approved for the treatment of MCL in Japan or the EU.

As part of an extensive clinical development programme, Calquence is currently being evaluated as a single treatment and in combination with standard-of-care chemoimmunotherapy for patients with multiple B-cell blood cancers, including CLL, MCL and diffuse large B-cell lymphoma.

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On January 16, 2025 Silexion Therapeutics (NASDAQ: SLXN), a clinical-stage biotech advancing RNA interference (RNAi) therapies for KRAS-driven cancers, reported compelling new preclinical data for SIL-204, its next-generation siRNA candidate (Press release, Silexion Therapeutics, JAN 16, 2025, View Source [SID1234649764]). These findings reaffirm the company’s innovative approach to addressing some of the most challenging cancers, including pancreatic cancer, which is marked by KRAS mutations in over 90% of cases.

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The newly released data reveal significant synergy between SIL-204 and first-line chemotherapy agents, including 5-fluorouracil, irinotecan, and gemcitabine. In human pancreatic tumor cell models harboring KRAS G12D mutations, SIL-204 amplified the efficacy of these standard therapies, resulting in greater reductions in cancer cell confluence compared to chemotherapy alone. This underscores SIL-204’s potential to enhance treatment regimens for pancreatic cancer and other KRAS-driven cancers, potentially addressing a substantial unmet medical need.

Building on the success of its first-generation LODER platform, which improved overall survival in Phase 2 trials, SIL-204 takes Silexion’s RNAi approach further by targeting a broader spectrum of KRAS mutations. With toxicology studies set to begin soon and Phase 2/3 trials planned for 2026, Silexion remains on track to advance its groundbreaking candidate into the clinic.

Shortly releasing this new data, Silexion also announced the pricing of a $5 million public offering to support its preclinical and clinical efforts. While this may introduce near-term dilution, if the offering is to close, the additional capital seems to bolster the company’s ability to drive innovation and achieve key clinical milestones as it moves forward.

As KRAS-driven cancers continue to be among the most aggressive and elusive to treat, Silexion’s progress with SIL-204 positions it as an important innovator to watch in the precision oncology space, offering hope for transformative therapies that could redefine cancer care.

On January 16, 2025 Prelude Corporation (PreludeDx), a leader in precision diagnostics for early-stage breast cancer, reported that the U.S. Food and Drug Administration (FDA) granted Breakthrough Device designation for its DCISionRT test (Press release, PreludeDx, JAN 16, 2025, View Source [SID1234649763]).

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DCISionRT provides individualized risk assessment and predicts the benefit of radiation therapy (RT) for women diagnosed with ductal carcinoma in situ (DCIS), also known as Stage 0 breast cancer. DCISionRT represents a significant advancement in DCIS patient care by combining tumor biology with clinicopathologic factors to deliver personalized results. The test analyzes seven protein biomarkers and four clinical factors to generate a Decision Score that helps physicians identify which patients are most likely to benefit from RT and can help reduce over- and under-treatment.

"DCISionRT addresses an unmet need for DCIS patients by answering the questions, ‘Do I need radiation therapy?’, and ‘will I benefit?’. DCISionRT helps patients and their physicians to make a better and more informed treatment decision." says Dan Forche, President and CEO of PreludeDx.

The test is designed for women aged 30-85 with DCIS and:

Predicts the benefit of radiation therapy after breast conserving surgery (BCS)
Is Prognostic for 10-year risk of breast cancer recurrence
Identifies patients with residual risk even after BCS and radiation therapy
The FDA’s Breakthrough Device designation is reserved for medical devices that provide for more effective treatment or diagnosis, and offer significant advantages over existing approved or cleared alternatives. Breakthrough Devices will receive priority review by the FDA, which can significantly shorten the time it takes to get approval.

Forche continued, "We will continue to work closely with the FDA and we remain committed to providing access to advanced precision diagnostics in breast cancer care that improve patient outcomes through new and innovative tools."

About DCISionRT for Breast DCIS

DCISionRT is the only risk assessment test for patients with ductal carcinoma in situ (DCIS) that predicts radiation therapy benefit. Patients with DCIS have cancerous cells lining the milk ducts of the breast, but they have not spread into surrounding breast tissue. In the US, over 60,000 women are newly diagnosed with DCIS each year. DCISionRT, developed by PreludeDx on technology licensed from the University of California San Francisco, and built on research that began with funding from the National Cancer Institute, enables physicians to better understand the biology of DCIS. The test provides a DecisionScore that identifies a woman’s risk as low, elevated, or residual risk. Unlike other risk assessment tools, the DCISionRT test combines protein expression from seven biomarkers and four clinicopathologic factors, and uses a non-linear algorithm to account for multiple interactions between individual factors in order to better interpret complex biological information. DCISionRT’s intelligent reporting provides a woman’s recurrence risk after breast conserving surgery alone and with the addition of radiation therapy. In turn, this new information may help patients and their physicians to make more informed treatment decisions.

On January 16, 2025 Caris Life Sciences (Caris), a leading next-generation AI TechBio company and precision medicine pioneer, reported a strategic and multi-faceted collaboration with Ontada, a business dedicated to oncology real-world evidence, clinical education and point of care technologies, to advance molecular research and cancer care, enhance the healthcare delivery system and ultimately drive precision medicine by supporting life sciences companies in the development of next-gen oncology therapies (Press release, Caris Life Sciences, JAN 16, 2025, View Source [SID1234649762]).

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"Rooted in a commitment to rigorous science and cancer care, the collaboration between Caris and Ontada includes strategic pillars spanning the development and delivery of multimodal data solutions, innovative research strategies and data-driven practices to provide actionable cancer care intelligence," said Caris President David Spetzler, MS, PhD, MBA. "By seamlessly integrating key entities of research, biopharma and patients, we collectively aim to revolutionize cancer research, drive innovation, advance precision medicine and improve patient outcomes."

"By bringing together two of the most extensive clinical and genomic data sets in community oncology, we have developed a unique resource for life sciences companies. Our goal with this resource is to empower them to address complex questions, potentially leading to groundbreaking research and improved cancer care," said Christine Davis, Ontada President. "Given the rapid evolution of oncology, this collaboration enables us to deliver insights more quickly, conduct more robust research and continue advancing precision care."

The collaboration leverages Caris’ molecular-rich, multimodal database generated from over 6.5 million tests producing over 13 quadrillion datapoints, and Ontada’s industry-leading real-world oncology data representing over 2.4 million cancer patient records available for research across more than 80 tumor types derived largely from community settings where, according to the National Cancer Institute, an estimated 85% of cancer patients are treated. Bringing together a synergistic convergence of cancer care, diagnostics and drug development, the collaboration extends beyond a combined data solution to advance oncology treatment through joint research projects.

"Caris and Ontada will collaboratively work to bridge the gap between research and real-world application, creating a streamlined pathway from research and development to clinical practice to benefit patients with faster access to more informed treatment decisions, personalized therapies, clinical trials and improved outcomes," said Chairman of the Caris Precision Oncology Alliance, James Hamrick, MD, MPH. "This collaboration marks a transformative approach to cancer care, fostering innovation, efficiency and patient-centered outcomes in oncology."

On January 16, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported to have participated in the 43rd Annual J.P. Morgan Healthcare Conference (Press release, Innovent Biologics, JAN 16, 2025, View Source [SID1234649761]).

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During the conference, Dr. De-Chao Michael Yu, Founder, Chairman and CEO of Innovent, delivered a presentation highlighting 2025 as a pivotal year for significantly business growth and concreate steps in global innovation. These efforts will further strengthen the foundation for Innovent’s vision of becoming a global premier biopharma company.

Clear path to sustainable growth

Innovent has established itself as a leading brand in oncology, consistently gaining momentum with an expanding portfolio of synergistic products. Additionally, another key growth driver, the general biomedicine segment, features a highly competitive product lineup, poised to unlock the substantial opportunities in chronic disease areas.

The company remains confident in achieving its domestic product revenue target of 20 billion RMB by 2027. Alongside rapid business growth, Innovent continues to enhance operational efficiency through effective and lean management practices, ensuring sustainable and healthy operating model.

Focus on world-class technology platforms and key therapeutic areas

Innovent Academy, the company’s innovation engine, has built a world-class technology platform, encompassing ScFv engineering, T cell engager (TCE), VHH bispecific antibodies, Topo1i ADC, dual payload ADC, and antibody peptide conjugates (APC). These platforms have consistently delivered innovative molecules, providing a driving force for the company’s long-term development.

In particular, Innovent combines its world-class antibody engineering and multiple sets of differentiated linker payload technologies to create the TOPO1i ADC technology platform (SoloTx) and dual payload ADC technology platform (DuetTx), producing a pipeline of potential best-in-class (BIC) or first-in-class (FIC) ADC candidates.

The company has so far advanced 8 ADC candidates into clinic trials, supported by efficacy and safety data from over 600 patients, with multiple ADCs receiving breakthrough therapy designation (BTD). This further validates the differentiated advantage of the company’s ADC platform technology and its strong clinical execution.

Innovent continues to focus on high-potential therapeutic areas in oncology and general biomedicine. The "PD-1+precision therapies" pipeline strengthens its leadership in oncology, while the "IO+ADC" strategy is set to transform cancer treatment. Meanwhile, its general biomedicine pipeline covers next generation treatments for autoimmune, cardiovascular and metabolic, and ophthalmic diseases, aiming to elevate treatment standards for diverse patient populations.

Embracing new opportunities in global innovation

Innovent Academy’s advancements have paved the way for a globally competitive pipeline of next generation IO and ADC candidates. The company plans to expand into innovative ADCs, bispecific (multi-specific) antibodies, and next-generation autoimmune and CVM therapies for global development.

IBI343 (CLDN18.2 ADC): Phase 3 multi-regional clinical trial (MRCT) has been initiated in China and Japan for gastric cancer. Pancreatic cancer MRCT clinical Phase 1 data shows positive efficacy and safety signals in Chinese patients and has started patient enrollment in the U.S. Pivotal clinical trials are anticipated in 2025, subject to PoC validation.
IBI363：This first-in-class PD-1/IL-2α-biased bispecific antibody has shown promising Phase 1 clinical data, obtained from hundreds of patients in IO resistant non-small cell lung cancer (NSCLC), melanoma, and IO unresponsive "cold tumor" colorectal cancer (CRC). This points to its potential as the next generation IO cornerstone drug. Innovent is following up on the Phase 1b/2 expansion cohorts of these cancer types. Pivotal clinical studies in IO-resistant advanced squamous NSCLC and IO-naïve advanced melanoma are planned to launch in China in 2025, subject to PoC data and regulatory communication. A Phase 2 clinical study is ongoing in the U.S. and will further expand into cohorts for NSCLC, CRC, and melanoma.
IBI3009 (DLL3 ADC): Through global licensing collaboration with Roche, Innovent aims to accelerate the development of this potentially best-in-class DLL3 ADC for small cell lung cancer patients worldwide.
2025 outlook: unlocking growth opportunities

Looking ahead in 2025, the company anticipates a year of rapid growth, driven by six new drug launches and further advancements in commercialization across oncology and general biomedicine. Key highlights include:

Mazdutide (GCG/GLP-1): Expected approvals for weight loss and type 2 diabetes indications in the first and second half of 2025, respectively, will provide a best-in-class GCG/GLP-1 dual agonist drug offering robust weight loss and glucose reduction, substantial liver fat reduction as well as comprehensive metabolic benefits for the vast obese, overweight and diabetes population;
Teprotumumab (IGF-1R): Anticipated launch as China’s first anti-IGF-1R monoclonal antibody for thyroid eye disease (TED), addressing a 60-year treatment gap.
Picankibart (IL-23p19): Approval anticipated by late 2025. Picankibart is the first globally to report that over 80% of subjects achieved PASI 90 (≥90% improvement in psoriasis area and severity index) within 16 weeks of treatment. It also demonstrates clear advantages, including sustained long-term efficacy, effective in patients resistant to IL-17 inhibitors, and flexibility with seasonal dosing intervals. Picankibart is poised to deliver exceptional comprehensive benefits to psoriasis patients in China.
As the company advances key cornerstone products in its pipeline, we are actively expanding the development of mazdutide, teprotumumab, and picankibart into additional indications to maximize the portfolio’s value. Building on this solid foundation, next-generation candidates are gradually entering clinical development, aiming to address global challenges related to aging and chronic disease burden. These innovations focus on extending dosing intervals, oral delivery, and novel mechanisms of action.

Looking ahead to 2025, the company plans to submit NDAs or conduct ongoing registrational trials for seven drugs, while initiating pivotal or registrational trials for seven innovative pipeline candidates, pending PoC results. Additionally, molecules with global potential and novel mechanisms of action (MoAs) will progress into PoC and first-in-human studies. These efforts solidify Innovent’s vision of "growing into a global premier biopharma company."