\nSummit Therapeutics Inc. (NASDAQ: SMMT) today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding the Biologics License Application (BLA) for ivonescimab in combination with platinum-containing chemotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), who have received prior epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy. Ivonescimab is a novel PD-1 x VEGF bispecific antibody.<\/p>\n
\n\u201cAs a cancer survivor, I understand firsthand how important it is for patients to have access to multiple treatment options, particularly when they are facing diseases with significant unmet medical needs,\u201d emphasized Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit Therapeutics. \u201cBehind every diagnosis is a person, a family, and a community hoping for more time, more possibilities, and a better future. I know that hope is not simply an emotion; it is the possibility that another treatment, another scientific breakthrough, or another therapeutic option may make a meaningful difference in someone\u2019s life. Every additional treatment option matters. It represents another opportunity for patients and their families, especially those who have exhausted existing therapies or have limited alternatives. Our responsibility as an industry is to continue advancing science, challenging conventional thinking, and bringing innovative medicines to patients in need. For me, our mission is deeply personal to bring our innovative medicine to patients who may benefit most.\u201d<\/p>\n
\nThe CRL indicates that the BLA cannot be approved in its present form, as the FDA determined that substantial evidence of effectiveness is not established in the absence of a statistically significant overall survival (OS) improvement. The FDA indicated that the progression-free survival (PFS) benefit in the absence of a statistically significant OS benefit does not support a positive benefit-risk profile in support of approval.<\/p>\n
\nCurrently, there are no FDA-approved regimens that have demonstrated a statistically significant OS benefit in this patient setting. In the primary analysis for OS, ivonescimab in combination with chemotherapy showed a positive trend without achieving a statistically significant result. In a post-hoc analysis, longer-term follow-up of western patients demonstrated a consistent OS benefit across regions with a hazard ratio of 0.76 in the full population, the Asian patients, and the western patients.<\/p>\n
\nThe BLA was supported by data from HARMONi<\/a>, a global, randomized, double-blind Phase III clinical trial evaluating ivonescimab combined with platinum-containing chemotherapy compared with placebo combined with platinum-containing chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who were previously treated with a third-generation EGFR TKI. The HARMONi study has two primary endpoints: PFS and OS. HARMONi met its PFS primary endpoint, becoming the first global Phase III study of an immunotherapy-based regimen to show a statistically significant PFS improvement in this setting. The primary PFS analysis was also supported by longer-term follow-up in a post-hoc analysis, which demonstrated a consistent magnitude of benefit with more mature data of western patients.<\/p>\n \nIvonescimab in combination with chemotherapy demonstrated an acceptable and manageable safety profile, which was consistent with previous studies. Ivonescimab plus chemotherapy was well-tolerated with no new safety signals and comparable rates of discontinuation and death between both arms. There were 16 patients (7.3%) who discontinued ivonescimab due to treatment-related adverse events (TRAEs) compared to 11 patients (5.0%) who discontinued placebo due to TRAEs. There were four patients (1.8%) in the ivonescimab plus chemotherapy arm and five patients (2.3%) in the chemotherapy alone arm who died as a result of TRAEs in this Phase III study.<\/p>\n \n\u201cWe are disappointed for patients and their families awaiting additional treatment options in this setting,\u201d said Robert W. Duggan, Chairman and Co-Chief Executive Officer of Summit. \u201cWe chose to pursue an ivonescimab regimen here based on the opportunity to provide another treatment option to help patients in need. In doing so, we believe the global HARMONi study provided the basis for a treatment option that these patients needed.\u201d<\/p>\n \n\u201cWith five positive Phase III studies between Summit and Akeso, nothing changes with respect to our ever-growing belief in the opportunity for ivonescimab and our determination to advance ivonescimab\u2019s development,\u201d continued Robert Duggan. \u201cOur mission remains to improve outcomes for patients facing significant unmet needs, which is work worth doing, and we will continue through our expansive clinical development program.\u201d<\/p>\n \nSummit is currently developing ivonescimab in NSCLC, colorectal cancer (CRC), urothelial carcinoma (UC), and renal cell carcinoma (RCC), specifically conducting multiregional Phase II or Phase III clinical trials in the following proposed indications or settings beyond the HARMONi study:<\/p>\n \nIn addition, Summit is collaborating with other biopharmaceutical companies to test ivonescimab in combination with other novel compounds, including with:<\/p>\n \nFinally, Summit is collaborating with two cooperative groups to evaluate ivonescimab in Phase III studies including biliary tract cancer (BTC) and head and neck squamous cell carcinoma (HNSCC), including with:<\/p>\n \nIvonescimab is an investigational therapy that is not approved by any regulatory authority in Summit\u2019s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024. Currently, there are no PD-1 x VEGF bispecific antibodies approved in the U.S.<\/p>\n About Ivonescimab<\/b><\/p>\n \nIvonescimab, known as SMT112 in Summit\u2019s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 outside of Summit\u2019s license territories, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. By design, ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF.<\/p>\n \nThis design is intended to differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Summit believes ivonescimab\u2019s specifically engineered tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al<\/i>, iScience, 2025). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al<\/i>, iScience, 2025) increasing to approximately 10 days at steady state dosing, is to improve upon previously established efficacy thresholds, side effects, and safety profiles associated with prior approved drugs to these targets.<\/p>\n \nIvonescimab was invented by Akeso Inc. (HKEX Code: 9926.HK) and is currently utilized in multiple Phase III clinical trials. Over 5,000 patients have been treated with ivonescimab in clinical studies globally, and over 100,000 patients when considering those treated in a commercial setting in China, as noted by Akeso.<\/p>\n \nIvonescimab is an investigational therapy that is not approved by any regulatory authority in Summit\u2019s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024.<\/p>\n About Summit Therapeutics Inc.<\/b><\/p>\n \nSummit Therapeutics Inc. is a biopharmaceutical oncology company focused on the discovery, development, and commercialization of patient-, physician-, caregiver- and societal-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs.<\/p>\n \nSummit was founded in 2003 and the company\u2019s shares are listed on the Nasdaq Global Market (symbol “SMMT”). Summit is headquartered in Miami, Florida, with additional offices in Palo Alto, California, Princeton, New Jersey, Dublin, Ireland, and Oxford, UK.<\/p>\n \nFor more information, please visit https:\/\/www.smmttx.com<\/a> and follow Summit on X @SMMT_TX<\/a>.<\/p>\n Summit Forward-Looking Statements<\/b><\/p>\n \nAny statements in this press release about the Company\u2019s future expectations, plans and prospects, including but not limited to, statements about the clinical and preclinical development of the Company\u2019s product candidates, entry into and actions related to the Company\u2019s partnership with Akeso Inc. and other collaborations, the Company’s anticipated spending and cash runway, the therapeutic potential of the Company\u2019s product candidates, the potential commercialization of the Company\u2019s product candidates, the timing of initiation, completion and availability of data from clinical trials, the potential submission of applications for marketing approvals, the expected timing of BLA submissions or FDA decisions, potential acquisitions, statements about the previously disclosed At-The-Market equity offering program (\u201cATM Program\u201d), or the AstraZeneca private placement, the expected proceeds, uses thereof and possibility that the proceeds will not be sufficient to fund operations as long as anticipated, dilution to existing stockholders and potential adverse effects on the market price of the Company\u2019s common stock, including from future sales by AstraZeneca, AstraZeneca\u2019s ownership and contractual rights, including Third Party acquisition participation, registration rights and potential conflicts of interest, the Company\u2019s reliance on third parties for the supply of third party products and other contributions to certain combination clinical trials, the Company\u2019s estimates regarding stock-based compensation, and other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the Company\u2019s ability to sell shares of our common stock under the ATM Program, the conditions affecting the capital markets, general economic, market, industry, or political conditions, including the effects of geopolitical developments, domestic and foreign trade policies, and monetary policies, the results of our evaluation of the underlying data in connection with the development and commercialization activities for ivonescimab, the outcome of discussions with regulatory authorities, including the Food and Drug Administration, the uncertainties inherent in the initiation of future clinical trials, availability and timing of data from ongoing and future clinical trials, the results of such trials, and their success, global public health crises, that may affect timing and status of our clinical trials and operations, whether preliminary results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials or preclinical studies will be indicative of the results of later clinical trials, whether business development opportunities to expand the Company\u2019s pipeline of drug candidates, including without limitation, through potential acquisitions of, and\/or collaborations with, other entities occur, expectations for regulatory approvals, laws and regulations affecting government contracts and funding awards, availability of funding sufficient for the Company\u2019s foreseeable and unforeseeable operating expenses and capital expenditure requirements and other factors discussed in the “Risk Factors” and \u201cManagement\u2019s Discussion and Analysis of Financial Condition and Results of Operations\u201d sections of filings that the Company makes with the Securities and Exchange Commission. Summit defines a \u201cpositive study\u201d as a clinical study with one or more prespecified primary endpoints in which one of those endpoints achieves a statistically significant benefit according to the protocol or statistical analysis plan. Any change to our ongoing trials could cause delays, affect our future expenses, and add uncertainty to our commercialization efforts, as well as to affect the likelihood of the successful completion of clinical development of ivonescimab. Accordingly, readers should not place undue reliance on forward-looking statements or information. In addition, any forward-looking statements included in this press release represent the Company\u2019s views only as of the date of this release and should not be relied upon as representing the Company\u2019s views as of any subsequent date. The Company specifically disclaims any obligation to update any forward-looking statements included in this press release.<\/p>\n \nSummit Therapeutics and the Summit Therapeutics logo are registered trademarks, of Summit Therapeutics Inc. and\/or its affiliates in the USA. \u00a9 2026 Summit Therapeutics Inc. All Rights Reserved.<\/p>\n View source version on businesswire.com: <\/span>https:\/\/www.businesswire.com\/news\/home\/20261115117181\/en\/<\/a><\/span><\/p>\n Summit Therapeutics\u2019 Media & Investor Contacts: \nTracy Jones investors@smmttx.com KEYWORDS:<\/b> United States North America Florida<\/p>\n INDUSTRY KEYWORDS:<\/b> Science Biotechnology Research Pharmaceutical Oncology Health FDA Clinical Trials<\/p>\n\n
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Nathan LiaBraaten
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Senior Director, Investor Relations<\/p>\n
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Director, Media & Public Relations<\/p>\n
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media@smmttx.com<\/a><\/p>\n
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