Pertuzumab

iStock, Sean Pavone Beginning this week in Chicago, the American Association for Cancer Research’s annual conference will feature presentations that could have far-reaching implications for breast and blood cancers and more. Kicking off Friday and running through June 3 at McCormick Place Convention Center in Chicago, the 2025 annual meeting of the American Association for Cancer Research will include some of the most cutting-edge developments in cancer, which experts believe could have far-reaching implications across the industry and for medical practice. “As we head into the 2025 ASCO Annual Meeting, there are several key breast cancer trials that reflect major advancements in how we approach treatment,” Jason Mouabbi, assistant professor of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center, told BioSpace in an email. Meanwhile, Lore Gruenbaum, chief scientific officer of The Leukemia & Lymphoma Society, is looking forward to a host of blood cancer-related presentations, including those that explore minimal residual disease (MRD) testing in multiple myeloma—a development she called “exciting.” MRD testing, Gruenbaum added, “will likely change clinical development strategies for novel agents and may provide significant time savings” for drugmakers. Besides breast and blood cancers, many of the late-breakers at ASCO 2025 are focused on melanoma, gastric, prostate and lung cancers. Breast and Blood Cancers Amid the variety of presentations at ASCO 2025, the buzz around breast and blood cancers stands out. One such attention-grabber is Takeda and Protagonist Therapeutics’ investigational hepcidin mimetic rusfertide, which the partners are developing for polycythemia vera, a rare but potentially deadly blood malignancy. “Rusfertide is a promising emerging treatment option,” Gruenbaum told BioSpace, noting that the molecule could provide an effective alternative for patients who do not adequately respond to standard therapies. In March, Takeda and Protagonist released topline data from their Phase III VERIFY study, which showed that rusfertide met its primary efficacy endpoint, eliciting treatment responses in 77% of patients versus 33% of placebo counterparts. Rusfertide likewise aced key secondary endpoints, including reducing phlebotomies, boosting hematocrit control and improving patient-reported outcomes. While Gruenbaum had not yet seen the ASCO abstract , “the data available so far indicate the potential for Rusfertide to significantly reduce the need for phlebotomies and improve hematocrit control in patients with polycythemia vera,” she said, adding that an improvement in quality of life data “could be very meaningful to patients.” VERIFY has been granted a plenary spot at the conference. In breast cancer, several presentations have drummed up considerable pre-conference interest. One of these is AstraZeneca’s Phase III SERENA-6 trial, which MD Anderson’s Mouabbi said is “one of the most anticipated studies at ASCO.” SERENA-6 combines the pharma’s oral SERD camizestrant with a CDK4/6 blocker to treat patients with HR-positive, HER2-negative advanced breast cancer with emergent ESR1 mutations. High-level outcomes posted in February showed the camizestrant regimen significantly improved progression-free survival in these patients versus standard-of-care aromatase inhibitors. AstraZeneca did not reveal specific data at the time—but will do so now at ASCO. “This trial is especially compelling because it’s the first to show a statistically significant improvement in progression-free survival in this setting, without requiring radiographic progression,” Mouabbi told BioSpace . “It’s a potential paradigm shift in how we manage endocrine resistance.” Like VERIFY, SERENA-6 is also a plenary presentation . AstraZeneca will also have additional Phase III data from DESTINY-Breast09, which will be “another standout” presentation, according to Mouabbi. The trial centers on the antibody-drug conjugate Enhertu—which AstraZeneca is developing in partnership with Daiichi Sankyo—testing it with or without Roche’s Perjeta as a first-line option in patients with HER2-positive metastatic breast cancer. Last month, the partners announced that Enhertu significantly improved progression-free survival in Destiny-Breast09, though again without providing specific data. “This is a significant development for HER2+ patients, offering a less chemotherapy-intensive option with robust efficacy,” Mouabbi said. Other notable breast cancer presentations, according to Mouabbi, include Merck and Gilead’s ASCENT-04/KEYNOTE-D19 , which combines the anti-TROP2 ADC Trodelvy with the mega-blockbuster Keytruda, and Pfizer and Arvinas’ VERITAC-2 trial, which in March returned mixed results for their investigational PROTAC degrader vepdegestrant. Bi – and Trispecifics Aside from specific presentations, experts are also looking forward to advancements in various treatment modalities. Such developments could give rise to new treatment opportunities for what Scott Kopetz, professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, called “cold tumors”—those that are unlikely to elicit an immune response and are, in turn, less susceptible to immunotherapies. In particular, Kopetz has his eye on bispecific antibodies, which he said could usher in “a new era in VEGF-targeted therapies.” These emerging therapies “not only inhibit angiogenesis [the formation of new blood vessels] but also enhance immune responses,” he continued, noting that such a mechanism could lead to “promising efficacy and safety in advanced solid tumors.” As a result, bispecific antibodies could yield “potential breakthroughs” in the treatment of immunologically cold tumors, such as castration-resistant prostate and gallbladder cancers, Kopetz said. According to Gruenbaum, bispecifics, and now also trispecific antibody platforms, could likewise open up new treatment avenues for blood cancers. ASCO, she continued, will witness initial clinical data for two trispecifics, including Johnson & Johnson’s JNJ-5322 and Ichnos Glenmark Innovation’s ISB-2001, both of which are being developed for relapsed/refractory multiple myeloma. There is also now a growing number of bispecific therapies for blood cancers, some of which are inching toward regulatory approval, which they could secure “in the near future,” Gruenbaum said. Drug developers are also starting to move these agents into earlier lines of therapy, she added. For David Piwnica-Worms, chair of Cancer Systems Imaging at MD Anderson, ASCO 2025 will be an opportunity to learn about some of the latest developments in radiopharmaceuticals. “We’re really seeing two trends,” he told BioSpace in an email. The first deals with identifying biomarkers for cancers earlier in the disease cycle, while the second is focused on identifying novel isotopes. Both of these trends, Piwnica-Worms said, underscore that “this is an exciting time” for the radiopharma space, since “the field is rapidly expanding with new isotopes and new molecular targets.” China in Focus In a May 21 note to investors, analysts at Truist Securities made an astute observation: nearly a third of presentations at ASCO involve assets that came from Chinese companies. The considerable presence of China at the conference reflects “the country’s increase in R&D efforts, as per the Truist note. “China’s biotech innovation footprint has clearly expanded on the global stage.” Christiana Bardon, co-managing partner at biotech investment firm MPM BioImpact, made a similar observation. In an email to BioSpace , she pointed out that whereas Chinese companies “historically have focused on making ‘fast-follower drugs,” they are now taking an active leadership role in innovation and are advancing “disruptive, first-in-class medicines.” Bardon pointed to Summit Therapeutics’ and its Chinese partner Akeso’s PD-1/VEGF bispecific ivonescimab, “which may displace Keytruda’s dominant position in cancer immunotherapy.” According to Bardon, many Big Pharma players have been playing catch-up to Summit and Akeso in this space: “Since Summit Therapeutics in-licensed ivonescimab from Akeso, we have seen BioNTech, Merck, and Pfizer reach for additional PD(L)1 x VEGF assets from China.” Bardon sees no real problem with this, however. “Increasing innovation will ultimately benefit patients, regardless of where it originates,” she said. Paul Moore, chief scientific officer at Zymeworks, agreed, noting that China’s ascent as a worldwide leader in cancer innovation creates a “more competitive environment” across the oncology space, in turn pushing U.S. companies to be more “innovative and efficient.” Drugmakers, Moore offered, should become more “intentional” about their pipelines, look for opportunities to differentiate themselves and “prioritize thoughtful trial design.” Studies should pay particular consideration to the underlying biological mechanisms of diseases, while also taking advantage of companies’ respective “unique areas of expertise,” he added. Such an approach, Moore explained, is likely to result in drug candidates “with novel biological mechanisms and strong clinical potential.” Development efficiency will no longer be enough, Moore added. “Real progress will come from therapies...that offer something new and impactful for patients.” In all, he said that healthy competition between global leaders in biopharma innovation could lead to a “steel-sharpens-steel phenomenon.”

Positive recommendation based on phase III INAVO120 data showing ItovebiTM (inavolisib) in combination with palbociclib and fulvestrant more than doubled progression-free survival in the first-line setting1 The Itovebi-based regimen also demonstrated a statistically significant and clinically meaningful benefit in overall survival (OS) in the final OS analysis Final OS data will be presented in an oral session at the 2025 American Society of Clinical Oncology Annual Meeting 23 May 2025 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Itovebi™ (inavolisib), in combination with palbociclib (Ibrance®) and fulvestrant, for the treatment of adult patients with PIK3CA-mutated, oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, following recurrence on or within 12 months of completing adjuvant endocrine treatment. If approved, the Itovebi-based regimen has the potential to transform the standard of care in this first-line setting, where treatments are currently limited.1 A final decision regarding the approval is expected from the European Commission in the near future. “The positive CHMP recommendation for the Itovebi-based regimen represents a significant step towards providing people in the EU with PIK3CA-mutated, ER-positive advanced breast cancer with a targeted therapy in the first-line setting,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “This recommendation is further enforced by the recent final overall survival results from the INAVO120 study, showing the regimen can meaningfully extend survival.” The presence of a PIK3CA mutation, found in approximately 40% of hormone receptor (HR)-positive breast cancers, can make the disease more aggressive and worsen survival outcomes.2,3 This underscores the importance of testing for PIK3CA mutations prior to first-line treatment so that people with a poor prognosis can benefit from an effective, PI3K-targeted therapy as soon as possible. The CHMP’s positive opinion is based on the phase III INAVO120 results, published in the New England Journal of Medicine in October 2024, which showed a 57% reduction in the risk of disease worsening or death (progression-free survival [PFS]) with the Itovebi-based regimen compared with palbociclib and fulvestrant alone (15.0 months vs. 7.3 months; hazard ratio [HR]=0.43, 95% CI: 0.32-0.59, p1 The PFS benefit was consistent across all pre-specified subgroups, including people whose disease had spread to three or more locations, characterised as difficult-to-treat disease.1 The Itovebi-based regimen was well tolerated, with no new safety signals observed.1 Positive topline results from the final overall survival (OS) analysis, announced in January 2025, showed a statistically significant and clinically meaningful OS benefit with the Itovebi-based regimen. OS data were immature at the time of primary analysis, but a clear positive trend was observed (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338 (boundary of 0.0098)).1 The full results from the OS analysis will be presented in an oral session at the 2025 American Society of Clinical Oncology Annual Meeting. The Itovebi-based regimen is approved for the treatment of adults with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer in the United States, Switzerland, Canada, Australia, United Arab Emirates and China, with data from INAVO120 under review with other global health authorities. Beyond INAVO120, Itovebi is currently being investigated in three company-sponsored phase III studies (INAVO121, INAVO122, INAVO123), all in PIK3CA-mutated, locally advanced or metastatic breast cancer in various combinations.4-7 We are exploring additional studies in breast cancer and other tumour types with the hope of providing the benefit of this targeted therapy to more people with PIK3CA mutations. Itovebi is an oral, targeted treatment that has been shown to provide well-tolerated and durable disease control in people with advanced PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, who often have a poor prognosis and are in urgent need of new treatment options.1-3 Itovebi has been designed to help minimise the overall burden and toxicity of treatment and is differentiated from other PI3K inhibitors due to its high potency and specificity for the PI3K alpha isoform versus other isoforms, and unique mechanism of action that facilitates the degradation of mutated PI3K alpha.8,9 The INAVO120 study [NCT04191499] is a phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy and safety of Itovebi™ (inavolisib) in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.4 The study included 325 patients, who were randomly assigned to either the investigational or control treatment arm.4 The primary endpoint is progression-free survival, as assessed by investigators, defined as the time from randomisation in the clinical trial to the time when the disease progresses, or a patient dies from any cause.4 Secondary endpoints include overall survival, objective response rate, and clinical benefit rate.4 Beyond INAVO120, Itovebi is currently being investigated in three additional company-sponsored phase III clinical studies in PIK3CA-mutated, locally advanced or metastatic breast cancer in various combinations:5-7 in combination with fulvestrant versus alpelisib plus fulvestrant in HR-positive/HER2-negative breast cancer post cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and endocrine combination therapy (INAVO121; NCT05646862). in combination with pertuzumab plus trastuzumab for subcutaneous injection (SC) versus pertuzumab plus trastuzumab for SC and optional physician's choice of endocrine therapy as a maintenance treatment in HER2-positive disease (INAVO122; NCT05894239). in combination with a CDK4/6 inhibitor and letrozole versus placebo plus a CDK4/6 inhibitor and letrozole in the first-line setting in PIK3CA-mutated HR-positive/HER2-negative, endocrine-sensitive breast cancer (INAVO123; NCT06790693). HR-positive breast cancer is the most prevalent type of all breast cancers, accounting for approximately 70% of cases.10,11 A defining feature of HR-positive breast cancer is that its tumour cells have receptors that attach to one or both hormones – oestrogen or progesterone – which can contribute to tumour growth. People diagnosed with HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, creating a need for additional treatment options.11-13 The PI3K signalling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism of intrinsic resistance to standard of care endocrine therapy in combination with cyclin-dependent kinase 4/6 inhibitors.3 Roche has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough outcomes in human epidermal growth factor 2-positive and triple-negative breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including oestrogen receptor-positive breast cancer, which is a form of hormone receptor-positive breast cancer, the most prevalent type of all breast cancers.10,11 Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. References [1] Turner NC, et al. Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer. NEJM. 2024;391(17):1584-96. [2] Fillbrunn M, et al. PIK3CA mutation status, progression and survival in advanced HR+/HER2- breast cancer: a meta-analysis of published clinical trials. BMC Cancer. 2022;22:1002. [3] Anderson E, et al. A Systematic Review of the Prevalence and Diagnostic Workup of PIK3CA Mutations in HR+/HER2– Metastatic Breast Cancer. Int J Breast Cancer. 2020;2020:3759179. [4] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer (INAVO120) [Internet; cited 2025 May]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT04191499. [5] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy (INAVO121) [Internet; cited 2025 May]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05646862. [6] ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer (INAVO122) [Internet; cited 2025 May]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05894239. [7] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib Plus CDK4/​6 Inhibitor and Letrozole vs Placebo + CDK4/​6i and Letrozole in Participants With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer (INAVO123) [Internet; cited 2025 April]. Available from: https://clinicaltrials.gov/study/NCT06790693. [8] Juric D, et al. A phase I/Ib study of inavolisib (GDC-0077) in combination with fulvestrant in patients (pts) with PIK3CA-mutated hormone receptor-positive/HER2-negative (HR+/HER2–) metastatic breast cancer. Presented at San Antonio Breast Cancer Symposium, 2020 December 7-10; San Antonio, USA. Abstract #P5-17-05. [9] Hong R, et al. GDC-0077 is a selective PI3K alpha inhibitor that demonstrates robust efficacy in PIK3CA mutant breast cancer models as a single agent and in combination with standard of care therapies. Cancer Res. 2018;78(4):4-14. [10] National Cancer Institute: Surveillance, Epidemiology and Ends Result Program. Cancer Stat Facts: Female Breast Cancer Subtypes [Internet; cited 2025 April]. Available from: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. [11] Lim E, et al. The natural history of hormone receptor-positive breast cancer. Oncology (Williston Park). 2012;26(8):688-94,696. [12] Tomas R and Barrios CH. Optimal management of hormone receptor positive metastatic breast cancer in 2016. Ther Adv Med Oncol. 2015;7(6):304-20. [13] Galipeau N, et al. Understanding key symptoms, side effects, and impacts of HR+/HER- advanced breast cancer: qualitative study findings. J Patient-Rep Outcomes. 2019;3(1):10. The content above comes from the network. if any infringement, please contact us to modify.