PD-L1 positive Non-Small Cell Lung Cancer

LaNova Medicines has advanced its PD-1xVEGF bispecific antibody to a first in-human trial in China after securing $42 million in a Series C1. The Shanghai-based biotech said Friday that it kicked off a Phase 1 test of the asset, dubbed LM-299, in people with advanced solid tumors. The company is also planning a trial in the US and is targeting an IND filing in the second half of the year. Interest in the PD-1xVEGF bispecific approach spiked earlier this year after Summit Therapeutics and Akeso’s ivonescimab beat Merck’s Keytruda in a Phase 3 trial in PD-L1-positive advanced non-small cell lung cancer (NSCLC) in China. A week later, BioNTech detailed positive Phase 2 results for its bispecific, BNT327, in patients in China with EGFR-mutant NSCLC. LaNova’s candidate is further behind, but the company said it is looking to “accelerate the development” of LM-299 with the help of the new funding. The Series C1 proceeds are also expected to support the advancement of a Phase 3 antibody-drug conjugate that targets claudin 18.2 and a monoclonal antibody that acts on CCR8. The monoclonal antibody is set to enter a Phase 2 trial in the US later this year, with the ADC expected to follow suit in the second half of 2025, the company said. The Series C1 was led by Sino Biopharmaceutical, with support from new investors Pudong Innovation Investment and Zhangjiang Haoheng, alongside existing investors. LaNova said it has already initiated a Series C2 financing.

Bristol Myers Squibb plans to “do a little bit more homework” as it works on the exact design of its phase 3 trial for Opdualag in PD-L1-high non-small cell lung cancer, Chief Medical Officer Samit Hirawat, M.D., said. More than two years after an initial FDA approval in melanoma, Bristol Myers Squibb is moving its PD-1/LAG-3 combo Opdualag into registrational testing in one of the most important oncology disease areas—first-line non-small cell lung cancer (NSCLC).The company has disclosed a phase 3 trial coded RELATIVITY1093 to evaluate Opdualag—a fixed combination of the PD-1 inhibitor Opdivo and the LAG-3 inhibitor relatlimab—plus chemotherapy in stage 4 or recurrent nonsquamous NSCLC cases with PD-L1 expression between 1% and 49%. The trial will adopt a higher dose of relatlimab than in Opdualag’s FDA-approved melanoma indication and will use Merck & Co.’s Keytruda and chemo as the comparator.Separately, BMS plans to initiate another phase 3 trial next year for Opdualag in first-line nonsquamous NSCLC patients with PD-L1 expressions of at least 50%, Chief Medical Officer Samit Hirawat, M.D., told Fierce Pharma in an interview.RELATIVITY1093 is ready to roll because “the signal is very clear” and the unmet medical need still exists in the PD-L1-low population, Hirawat said.“We don’t believe that the current standard of care is giving you the benefit of [progression-free survival] and overall response rate as what we have seen in our clinical trial,” Hirawat said. “So that is squarely a place where we wanted to go and fit and start the study as soon as possible.”In contrast, BMS is taking time to “do a little bit more homework” as it devises the exact design of its phase 3 for the PD-L1-high population, including on the utilization of chemotherapy, he said. When asked whether BMS is considering dividing the PD-L1-high population to focus on a subgroup based on eligibility for chemo, Hirawat said he’s “not ready to commit”  to such an approach. Development of Opdaulag has been “a slow march,” Hirawat acknowledged.“We didn’t straight away jump into [a] phase 3 trial in non-small cell lung cancer after we saw the melanoma data, which used to happen in the prior I-O world, because we really need to define how LAG-3 works, what the combinations would be and what the indication should be.” ESMO RELATIVITY-104 readout BMS’ latest decision is based on results from the phase 2 RELATIVITY-104 trial conducted in patients with previously untreated stage 4 or recurrent NSCLC. The trial did not include any enrollment criteria around levels of PD-L1 present in patients’ tumors. The story refers to the combo as Opdualag even though the dosage strengths of nivolumab and relatlimab evaluated in the trial are different from those in Opdualag’s FDA-approved melanoma indication.Among  PD-L1-negative patients enrolled in the part 2 efficacy portion of the trial (see table below for detailed data), the addition of relatlimab—at the 360-mg dose as selected from part 1—to Opdivo and chemo led to a slightly higher overall response rate (ORR), but the LAG-3-containing regimen performed slightly worse on progression-free survival (PFS), according to results shared at the European Society of Medical Oncology Congress 2024. Similarly, in patients with squamous disease, the Opdualag regimen showed a higher ORR but a shorter median PFS time.In terms of patients’ life expectancy, benefits of Opdualag were observed only in PD-L1-positive patients and in those with nonsquamous disease, Hirawat said.In PD-L1-low patients, those who took Opdualag and chemo showed an ORR of 60.7% and a median PFS of 9.8 months, whereas the Opdivo-chemo group experienced an ORR of 30% and PFS of 5.5 months, according to Hirawat.In PD-L1-high patients, Opdualag and chemo delivered an ORR of 54.5% and a median PFS of 13.8 months, versus 46.4% and 7.1 months for Opdivo and chemo.Among nonsquamous patients with PD-L1-positive tumors, the median PFS was 11.6 months for the LAG-3 group and 6.9 months for control, translating into a 45% reduction in the risk of progression or death.BMS took into consideration data from part 1 of the trial and also benchmarked all results with findings from other published trials, Hirawat said.RELATIVITY-104 Part 2 (Girard et al/ESMO24) Opdualag + chemoOpdivo + chemoORR (%)mPFS (mo)ORR (%)mPFS (mo)PD-L1-negative505.644.85.8PD-L1-low60.79.8305.5PD-L1-high54.513.846.47.1Squamous60.85.655.35.8Nonsquamous46.78.338.56 Shifting lung cancer landscape Previously, in the landmark KEYNOTE-189 trial conducted in first-line nonsquamous NSCLC. Keytruda and chemo led to a median PFS of 11.3 months in PD-L1-high patients and 9.4 months in PD-L1-low patients, according to an updated analysis published last year.BMS is advancing Opdualag into phase 3 testing as the NSCLC ground rapidly shifts under its feet. In LAG-3 alone, a phase 2/3 study that’s comparing the addition of Regeneron’s fianlimab on top of the company’s PD-1 inhibitor Libtayo and chemotherapy in advanced NSCLC is currently underway in phase 2. Regeneron has some early data at ESMO24 suggesting fianlimab might be better than BMS’ relatlimab in melanoma and is determined to prove that with an ongoing head-to-head phase 3 trial.Beyond the LAG-3 class, Akeso and Summit Therapeutics’ PD-1/VEGF bispecific antibody ivonescimab just beat Keytruda monotherapy in a head-to-head China phase 3 in first-line, PD-L1-positive NSCLC. Summit has already launched a phase 3 trial pitting ivonescimab and chemo against Keytruda and chemo in first-line squamous NSCLC.Merck, AstraZeneca and Gilead Sciences are developing their TROP2 antibody-drug conjugates in first-line NSCLC, too. BMS has recently in-licensed an EGFRxHER2 bispecific ADC from China’s SystImmune. The drug is being evaluated in NSCLC and breast cancer. On the flip side, the New Jersey pharma just terminated a deal for Agenus’ TIGITxCD96 bispecific antibody following multiple failures in the TIGIT class.“Each and every clinical trial is a step forward, not a step backward,” Hirawat said, “because it gives us an insight into how the landscape is evolving and what is to be learned.”

- Clinically meaningful objective response rate (ORR) of 63.3-76.7% observed with belrestotug + dostarlimab combinations, with confirmed ORR (cORR) at ~60% for every dose- >30% cORR difference between belrestotug + dostarlimab vs dostarlimab monotherapy- Belrestotug + dostarlimab safety profile broadly consistent with known safety profile of checkpoint inhibitor combinations- GALAXIES Lung-301, global Phase 3 registration study, enrolling in same indication and setting- iTeos to host a conference call on Monday, September 16, 2024 at 8:00am ET WATERTOWN, Mass. and GOSSELIES, Belgium, Sept. 14, 2024 (GLOBE NEWSWIRE) -- iTeos Therapeutics, Inc. (Nasdaq: ITOS) (“iTeos”), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients, today announced follow-up interim data from GALAXIES Lung-201, the Phase 2 platform study sponsored by iTeos’ development partner GSK, assessing the belrestotug + dostarlimab doublet in previously untreated, unresectable, locally advanced or metastatic PD-L1 high non-small cell lung cancer (NSCLC). “We are encouraged by this interim cut of GALAXIES Lung-201 data in which a clinically meaningful, investigator-assessed Objective Response Rate was observed with belrestotug in combination with dostarlimab in first-line, PD-L1 high non-small cell lung cancer patients. Further, with roughly 60 percent confirmed ORR at three distinct doses and a meaningful difference of 30 percent compared to dostarlimab alone, we believe this underscores the potential differentiation of our TIGIT:PD-1 doublet,” said Michel Detheux, Ph.D., president and chief executive officer of iTeos. “The improvement in depth of response in tumor measurement in patients treated with the doublet compared to those treated with PD-1 alone holds promising therapeutic potential for a patient population with limited options. We believe these encouraging data further support the recent initiation of GALAXIES Lung-301, the registrational Phase 3 trial assessing the TIGIT:PD-1 doublet in the same indication and setting. Based on these results, we are committed to leveraging our science to impact the lives of people living with cancer and are excited to see longer-term follow-up data in 2025.” “While checkpoint inhibitor therapies have played a significant role in how we treat non-small cell lung cancer, the medical community continues to look for new patient-centered treatment options to meaningfully improve this life-threatening condition,” said Brian Henick, M.D., interim director of experimental therapeutics and director of translational research in upper-aerodigestive malignancies in medical oncology of Columbia University Irving Medical Center. “The follow-up interim analysis from the GALAXIES Lung-201 study represent promising progress and the deep responses observed in the belrestotug + dostarlimab doublet provide a strong, consistent signal. We eagerly anticipate gaining further insights from this trial over the next year as the dataset matures.” Highlights of Interim GALAXIES Lung-201 DataAs of the June 7, 2024 data cutoff, the late-breaking interim data presented at the ESMO Congress were based on 124 patients eligible for safety and efficacy evaluation (modified intention-to-treat ≥5.6 months follow-up). Patients received dostarlimab or belrestotug + dostarlimab at the following dose levels: dostarlimab 500mg, belrestotug 100mg + dostarlimab 500mg (Dose A), belrestotug 400mg + dostarlimab 500mg (Dose B), and belrestotug 1000mg + dostarlimab 500mg (Dose C). Clinically meaningful improvement in the primary endpoint of ORR was observed consistently across each belrestotug + dostarlimab cohort (63.3% Dose A, 65.6% Dose B and 76.7% Dose C compared to 37.5% with dostarlimab alone). cORR, defined as complete or partial response confirmed by repeat imaging ≥4 weeks after response criteria first met, was roughly 60.0% for each dose compared to 28.1% cORR for dostarlimab alone.Of the patients with evaluable paired ctDNA samples (baseline and week 7), median ctDNA reduction was 65% for dostarlimab monotherapy compared to 55% for Dose A, 94% for Dose B, and 97% for Dose C.Belrestotug + dostarlimab led to an increase in immune-related adverse events compared to dostarlimab monotherapy, which were generally manageable. The safety profile of belrestotug in combination with dostarlimab has been broadly consistent with the known safety profile of combination therapy with checkpoint inhibitors. The most frequent treatment-related adverse events (≥15%) were skin and subcutaneous tissue disorders (50%) and endocrine disorders (26%), both commonly observed with immunotherapies. Response measure in mITTDostarlimab(N=32)Dose A:Dostarlimab +belrestotug100 mg(N=30)Dose B:Dostarlimab +belrestotug400 mg(N=32)Dose C:Dostarimab +belrestotug1000 mg(N=30)Median follow-up, months (range)7.0 (0.2–16.6)8.5 (0.3–14.3)8.5 (0.4–16.2)6.7 (2.4–9.7)ORR,1,2%n (95% CI)37.5%n=12 (21.1–56.3)63.3%n=19 (43.9–80.1)65.6%n=21 (46.8–81.4)76.7%n=23 (57.7–90.1)Complete response, n (%)0000Partial response, n (%)12 (37.5%)19 (63.3%)21 (65.6%)23 (76.7%)Stable disease, n (%)14 (43.8%)5 (16.7%)4 (12.5%)5 (16.7%)Progressive disease, n (%)2 (6.3%)4 (13.3%)3 (9.4%)2 (6.7%)Not evaluable/no assessment,3 n (%)4 (12.5%)2 (6.7%)4 (12.5%)0Confirmed ORR,2 %n (95% CI)28.1% n=9 (13.7–46.7)60.0% n=18 (40.6–77.3)59.4% n=19 (40.6–76.3)63.3%n=19 (43.9–80.1) 1. unconfirmed ORR; 2. PD-L1 high (TPS ≥50%) was determined locally or centrally by DAKO 22C3 or VENTANA SP263 assay; 3. patients who only had "not evaluable" post baseline assessments, those who had a best response of "not evaluable" per RECIST 1.1 criteria, or those where no post-baseline tumor assessment was performed; CI, confidence interval Conference Call DetailsThe follow-up interim data from GALAXIES Lung-201 will be discussed during a conference call and webcast presentation on Monday, September 16th, 2024 at 8:00AM ET. To register for the webcast presentation, please visit the Events section on the Investors page of the iTeos website at investors.iteostherapeutics.com. A webcast replay may be accessed on the Investors section of the iTeos website. Phase 2 GALAXIES Lung-201 Trial DesignThe Phase 2 GALAXIES Lung-201 study is a randomized, open-label, global platform study evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of novel immunotherapy combinations compared with immunotherapy monotherapy in participants with PD-L1 high (TPS ≥50%), previously untreated, unresectable, locally advanced or metastatic NSCLC.​ Arms and interventions in this study include: pembrolizumab (anti-PD-1) monotherapy, dostarlimab (anti-PD-1) monotherapy, belrestotug (anti-TIGIT) + dostarlimab doublet combination, and belrestotug + dostarlimab + nelistotug (anti-CD96) triplet combination. The primary endpoint of the study is investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Secondary endpoints include safety and additional efficacy measures such as progression free survival, overall survival, and duration of response. About iTeos Therapeutics, Inc.iTeos Therapeutics is a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients. iTeos Therapeutics leverages its deep understanding of tumor immunology and immunosuppressive pathways to design novel product candidates with the potential to restore the immune response against cancer. The Company’s innovative pipeline includes three clinical-stage programs targeting novel, validated immunosuppressive pathways designed with optimized pharmacologic properties for improved clinical outcomes, including the TIGIT/CD226 axis and the adenosine pathway. iTeos Therapeutics is headquartered in Watertown, MA with a research center in Gosselies, Belgium. About Belrestotug (EOS-448/ GSK4428859A)Belrestotug is an Fc active human immunoglobulin G1, or IgG1, monoclonal antibody (mAb) targeting T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT), an important inhibitory receptor which contributes to the suppression of innate and adaptive immune responses against cancer. As an optimized high-affinity, potent anti-TIGIT mAb, belrestotug is designed to enhance the antitumor response through a multifaceted immune modulatory mechanism by engaging with TIGIT and FcγR, a key regulator of immune responses which induces cytokine release and antibody dependent cellular cytotoxicity (ADCC). The therapeutic candidate is progressing in multiple indications in collaboration with GSK. Internet Posting of InformationiTeos routinely posts information that may be important to investors in the 'Investors' section of its website at www.iteostherapeutics.com. The Company encourages investors and potential investors to consult our website regularly for important information about iTeos. Forward-Looking StatementsThis press release contains forward-looking statements. Any statements that are not solely statements of historical fact are forward-looking statements. Words such as “believe,” “anticipate,” “plan,” “expect,” “will,” “may,” “intend,” “prepare,” “look,” “potential,” “possible” and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements relating to the potential benefits of belrestotug and the potential differentiation of belrestotug + dostarlimab; belrestotug’s market opportunity; and our plans and expected milestones, including having longer-term follow-up data from GALAXIES Lung-201 in 2025. These forward-looking statements involve risks and uncertainties, many of which are beyond iTeos’ control. Actual results could materially differ from those stated or implied by these forward-looking statements as a result of such risks and uncertainties. Known risk factors include the following: success in preclinical testing and early clinical trials does not ensure that later clinical trials will be successful, and early results from a clinical trial do not necessarily predict final results; interim and early data may change as more patient data become available and are subject to audit and verification procedures; the data for our product candidates may not be sufficient for obtaining regulatory approval to move into later stage trials or to commercialize products; iTeos may not be able to execute on its business plans, including meeting its expected or planned regulatory milestones and timelines, research and clinical development plans, and bringing its product candidates to market, for various reasons, some of which may be outside of iTeos’ control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, negative developments in the field of immuno-oncology, such as adverse events or disappointing results, including in connection with competitor therapies, and regulatory, court or agency decisions such as decisions by the United States Patent and Trademark Office with respect to patents that cover our product candidates; and those risks identified under the heading “Risk Factors” in iTeos’ Annual Report on Form 10-Q for the period ended June 30, 2024 filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by the Company which you are encouraged to review. Any of the foregoing risks could materially and adversely affect iTeos’ business, results of operations and the trading price of iTeos’ common stock. We caution investors not to place undue reliance on the forward-looking statements contained in this press release. iTeos does not undertake any obligation to publicly update its forward-looking statements other than as required by law. For further information, please contact: Investor Contact:Carl MauchiTeos Therapeutics, Inc.carl.mauch@iteostherapeutics.com Media Contact:media@iteostherapeutics.com