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Bispecific antibodies are one of the most active areas of cancer research, and pharmaceutical companies are busy striking deals to add them to their pipelines. One of the most talked about drugs at this year\u2019s annual meeting of the American Society of Clinical Oncology was a bispecific antibody that did not even have data presented at the conference.<\/p>\n
Summit Therapeutics announced preliminary Phase 3 data<\/a> for ivonescimab, which is designed to target the proteins EGFR and VEGF. The study, HARMONi, met a goal of showing statistically significant progression-free survival, but was just short of that threshold on the measure of overall survival. That\u2019s key because the FDA has made statistically significant overall survival a requirement for regulatory approval. The full results may yet reach that mark. Investors and clinicians paid close attention to Summit\u2019s data because they could read through to other drugs from this emerging class.<\/p>\n BioNTech has one such drug, a clinical-stage asset that is now the centerpiece of the company\u2019s combination strategy. The bispecific antibody, BNT327, binds to the proteins PD-L1 and VEGF-A. BioNTech aims to test this mechanism in combination with other modalities in its pipeline, such as its messenger RNA technology and antibody drug conjugates (ADCs).<\/p>\n Bristol Myers Squibb is buying into this strategy, paying BioNTech $1.5 billion up front<\/a> to collaborate on BNT327\u2019s development. Each company may also test drugs from their own pipelines in combination with the bispecific antibody.<\/p>\n BNT327 came from BioNTech\u2019s $800 million acquisition of the drug\u2019s developer, Biotheus. Ethan Smith, oncology director at Norstella, said that deal now looks like a shrewd one as growing interest and demand for these assets push the buying prices upward. Pfizer last month paid $1.25 billion up front to license rights to a bispecific antibody<\/a> targeting PD-1\/VEGF developed by China-based 3SBio (preliminary Phase 2 results<\/a> were reported at ASCO). But Smith and other industry observers believe BioNTech and BMS are well positioned with their partnered asset now in pivotal testing in lung cancer and entering a late-stage testing in triple negative breast cancer.<\/p>\n \u201cWith an extensive development plan for BNT327, including combinatorial trials, a differentiated mechanism of action (PD-L1), and Summit\u2019s HARMONi setback, analysts will closely monitor upcoming data,\u201d Smith wrote in an email. \u201cBMS will hope this asset will become the heir apparent to its immunotherapy blockbusters (e.g. Opdivo) that are nearing the end of their commercial lives.\u201d<\/p>\n If you were not able to make it to the ASCO meeting, here are some of the highlights we caught while on the ground at the largest cancer conference in the world:<\/p>\n Moving Immunotherapy Into Earlier Lines of Therapy<\/strong><\/p>\n AstraZeneca immunotherapy Imfinzi posted clinical data in gastric\/gastroesophageal cancer that could support its use as a new standard treatment in the perioperative setting \u2014 before and after surgery to remove cancer. A Phase 3 test evaluated the PD-L1 inhibitor plus chemotherapy as neoadjuvant (before) and adjuvant (after) treatment, followed by Imfinzi monotherapy. That regimen was compared to perioperative chemotherapy alone. Results showed Imfinzi and chemo led to a statistically significant 29% reduction<\/a> in the risk of disease progression, recurrence, or death compared to standard of care chemo.<\/p>\n \u201cWe got two thirds of patients who are free from both recurrence and progression two years later,\u201d Susan Galbraith, executive vice president of oncology R&D said during a briefing with journalists. \u201cThis is a considerable amount of time given a quarter of patients don\u2019t survive beyond two years with the current standard of care.\u201d<\/p>\n The Imfinzi arm also showed a statistically significant benefit in event-free survival, the first for an immunotherapy in this type of cancer in this setting, Leerink Partners analyst Andrew Berens wrote in a research note. Norstella\u2019s Smith said that these results are hoped to set a new standard of care, but he does not expect trial designs such as this will be seen in the future as the relative benefit of neoadjuvant and adjuvant immunotherapy cannot be ascertained.<\/p>\n Two Takes on Degrading a Key Breast Cancer Target<\/strong><\/p>\n Phase 3 data reported for experimental AstraZeneca drug camizestrant showed this therapy\u2019s potential to help patients whose breast cancer is driven by an ESR1 mutation in the gene that codes for the estrogen receptor. Camizestrant is an oral selective estrogen receptor degrader, or SERD.<\/p>\n ESR1 mutations are rare at the time of breast cancer diagnosis, found in less than 5% of patients, AstraZeneca\u2019s Galbraith said. But during standard first-line treatment with an aromatase inhibitor alongside a CDK4\/6 inhibitor, ESR1 mutations emerge in about 30% of patients, which drives drug resistance.<\/p>\n AstraZeneca\u2019s pivotal test for camizestrant employed an unusual treatment switching strategy. Patient blood was tested periodically for circulating tumor DNA (ctDNA). Upon detection of the ESR1 mutation, patients were allowed to switch out the aromatase inhibitor for the AstraZeneca drug. Results showed<\/a> camizestrant and CDK4\/6 inhibitors led to a median 16.0 months of progression-free survival compared to 9.2 months for the comparator arm. Galbraith said it\u2019s the first time ctDNA has been used in a Phase 3 study for this kind of monitoring, and the results mean that this type of drug intervention can be implemented earlier. Results were published<\/a> in the New England Journal of Medicine.<\/p>\n In an email, Citeline analyst Anna Simmons called the camizestrant results \u201cstriking.\u201d But she said the drug faces interpretation challenges due to complexities of the trial design and the cost and logistical burden of frequent ctDNA testing.<\/p>\n \u201cDespite these limitations, this pivotal trial data validate both ctDNA-based therapeutic decision-making and introduces SERDs into the endocrine-sensitive first-line setting, earning camizestrant [FDA] breakthrough designation in June 2025,\u201d Simmons said.<\/p>\n Meanwhile, partners Arvinas and Pfizer aim to take on ESR1 mutations with a different type of degradation. Their drug, vepdegestrant, is part of a class of therapies that work by a mechanism called targeted protein degradation. It\u2019s the first drug from this emerging modality to reach a Phase 3 clinical trial, and the oral drug was tested as a second-line treatment for metastatic ER positive, HER2 negative breast cancer.<\/p>\n In patients who had the ESR1 mutation, results showed a statistically significant and clinically meaningful improvement in progression-free survival, meeting the main clinical trial goal<\/a>. But in those who did not have that mutation, results were not statistically significant.<\/p>\n Leerink\u2019s Berens said his firm is unconvinced vepdegestrant is best in class. He noted that camizestrant\u2019s data could bring that AstraZeneca drug into first-line treatment of HR positive, HER2 negative advanced breast cancer, which in turn would decrease the ESR1 mutant population addressable by the Arvinas\/Pfizer drug. Citeline\u2019s Simmons agreed with that point, but she added that vepdegestrant showed better tolerability, suggesting a potential best-in-class safety profile. Based on the Phase 3 results, Arvinas submitted an application<\/a> seeking FDA approval of the drug for the treatment of ER positive, HER2 negative advanced breast cancer that has the ESR1 mutation.<\/p>\n Competition in EGFR-Targeting Lung Cancer Drugs<\/strong><\/p>\n Johnson & Johnson\u2019s bispecific antibody, Rybrevant, has moved up to first-line treatment of non-small cell lung cancer<\/a> driven by exon 20 insertion mutations to the protein EGFR. Other companies are vying to offer another choice for patients whose cancer exhibits this genetic signature but does not respond to the J&J therapy. Shanghai-based Dizal Pharma is furthest along with DZD6008. This oral drug is under FDA review with a regulatory decision expected in July; the key data supporting the regulatory submission were presented at last year\u2019s ASCO meeting. One issue with EGFR-targeting drugs is that they hit normal EGFR in addition to disease-driving mutant versions of the protein. Dizal co-founder and CEO Xialin Zhang told MedCity News that DZD6008 offers a safer way to address EGFR because it selectively targets the mutant form of that protein.<\/p>\n Cullinan Therapeutics makes a similar claim for zipalertinib, which it is developing in partnership with Taiho Oncology<\/a>. A pivotal Phase 2b study, which included patients previously treated with chemo and Rybrevant, met the main overall response rate goal<\/a>; side effects were classified as Grade 1 or 2 and were manageable. Based on these results, Cullinan said it plans a regulatory submission for zipalertinib in the second half of 2025. A Phase 3 study that could support frontline use is ongoing.<\/p>\n Who\u2019s Ahead in Head and Neck Cancer?<\/strong><\/p>\n Head and neck cancers can be treated with the Merck checkpoint inhibitor Keytruda, but response rates to this immunotherapy are low in this malignancy. Efforts to improve patient outcomes include drugs that go after EGFR, which is a known driver of head and neck cancers. Merus and Bicara Therapeutics are each pursuing the target with bispecific antibodies in clinical testing as first-line treatments alongside Keytruda. At the ASCO meeting, data updates from early-stage tests showed how well these drug combos are working.<\/p>\n Merus\u2019s petosemtamab is designed to bind to EGFR and LGR5. Interim Phase 2 results presented at ASCO showed a 60% overall response rate<\/a>; the median duration of response was 11 months with 17 responders still on treatment as of the data cutoff. At 12 months, the overall response rate was 79%.<\/p>\n Bicara\u2019s drug, ficerafusp alfa, binds to EGFR and TGF-beta. Updated Phase 1\/1b results were presented at ASCO<\/a> with at least two years of follow up in patients who were HPV negative. The confirmed objective response rate was 54%; the overall response rate was 64%. The median duration of response was 21.7 months.<\/p>\n In a research note, Leerink\u2019s Berens pointed out petosemtamab\u2019s higher 12-month overall survival rate compared with Bicara\u2019s drug at the same time point, which bodes well for the Merus drug\u2019s eventual overall survival duration. William Blair analyst Matt Phipps also gives the edge to Merus.<\/p>\n \u201cIn our view, Merus\u2019s petosemtamab continues to show a stronger profile overall, with robust efficacy regardless of HPV status and PD-L1 expression level, monotherapy activity, and a timeline advantage with Phase 3 studies beginning to read out next year,\u201d Phipps wrote in a research note.<\/p>\n Enhertu Shows Potential for Earlier Use in Breast Cancer<\/strong><\/p>\n For more than a decade, the standard of care for metastatic HER2-positive breast cancer has been the combination of taxane, trastuzumab, and pertuzumab, a regimen usually referred to as THP. Earlier this year, AstraZeneca and Daiichi Sankyo reported interim Phase 3 data showing their ADC, Enhertu<\/a>, led to statistically significant and clinically meaningful improvement in progression-free survival in the first-line setting. Details were presented at ASCO.<\/p>\n At the interim analysis, the Enhertu combination showed a median 40.7 months of progression free survival<\/a> compared to 26.9 months for the standard of care. Overall survival data were immature. The median duration of response was greater than three years. Norstella\u2019s Smith said the results represent the first improvement over standard of care in 10 years and a foray for an ADC into the frontline setting.<\/p>\n Enhertu also helped patients with gastric\/gastroesophageal cancer live 3.3 months longer<\/a> compared to Eli Lilly drug Cyramza and chemotherapy in the second-line setting. Smith said these results might make Enhertu the first HER2-directed therapy to improve overall survival in this setting. Dr. Emil Lou, a professor of medicine at the University of Minnesota who was not involved in clinical testing of Enhertu, said in an interview at ASCO that in clinical practice, oncologists have used either Cyramza and chemo or Enhertu for patients whose gastric cancer advances after first-line treatment.<\/p>\n \u201cNow we have more data to support that the antibody drug conjugate, despite its potential toxicities specific to that drug class, may be superior,\u201d Lou said. \u201cThat might solidify or firm up critical decision making for oncologists like me.\u201d<\/p>\n More ADCs of Interest<\/strong><\/p>\n \u2014AbbVie last month welcomed FDA approval of Emrelis<\/a>, an ADC that treats non-small cell lung cancer by targeting the protein c-Met.<\/strong> At ASCO, AbbVie presented Phase 1 data<\/a> for a next-generation c-Met-targeting ADC, telisotuzumab adizutecan. In a heavily pretreated patient population (a median three prior lines of therapies), AbbVie reported this ADC led to a 63% objective response rate. At the time of the data-cutoff, 54% of responders experienced a duration of response of at least six months.<\/p>\n \u2014Gilead Sciences\u2019 Trodelvy, a TROP2-targeting ADC, posted data<\/a> that could expand its use in triple negative breast cancer for patients whose disease is positive for PD-L1, the genetic signature addressed by Merck immunotherapy Keytruda.<\/strong> A study that tested Trodelvy with Keytruda as a first-line treatment showed 11.2 months of progression-free survival compared to Keytruda and chemotherapy.<\/p>\n \u2014The centerpiece of Genmab\u2019s $1.8 billion acquisition of ProFound Bio<\/a> last year was rinatabert sesutecan, or Rina-S, an ADC that targets folate receptor alpha.<\/strong> At ASCO, Genmab reported new data<\/a> from the dose-expansion cohort of a multi-part Phase 1\/2 study in endometrial cancer. With a median follow-up of 7.7 months, treatment with Rina-S led to a 50% confirmed objective response rate, including two complete responses. The median duration of response has not yet been reached. The company plans to advance the ADC to a Phase 3 test in endometrial cancer.<\/p>\n Photo: John Walton\/PA Images, via Getty Images<\/em><\/p>\n<\/p><\/div>\n\n","protected":false},"excerpt":{"rendered":" Bispecific antibodies are one of the most active areas of cancer research, and pharmaceutical companies are busy striking deals to add them to their pipelines. One of the most talked about drugs at this year\u2019s annual meeting of the American Society of Clinical Oncology was a bispecific antibody that did not even have data presented […]<\/p>\n","protected":false},"author":1,"featured_media":295512,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[97676,127141,127142,97673,97677,127143,104779,105770,97679,97674,127144,127145,127146,12380],"tags":[127149,18777,127147,127148,16974,11290,5894,6234],"dealstore":[],"offerexpiration":[],"class_list":["post-295511","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-american-society-of-clinical-oncology","category-antibody-drug-conjugate","category-astrazeneca","category-biopharma","category-biopharma-nl","category-bispecific-antibody","category-cancer","category-chicago","category-clinical-trials","category-daily","category-enhertu","category-johnson-johnson","category-oncology","category-pharma","tag-adcs","tag-asco","tag-bispecifics","tag-degraders","tag-dueling","tag-interest","tag-recap","tag-rise"],"yoast_head":"\n