On May 5, 2025 Phanes Therapeutics, Inc. (Phanes), a clinical stage biotech company focused on innovative drug discovery and development in oncology, reported that the first patient has been dosed in the clinical study of peluntamig in combination with Roche’s anti-PD-L1 monoclonal antibody atezolizumab (TECENTRIQ ) (Press release, Phanes Therapeutics, MAY 5, 2025, View Source [SID1234652526]). The study is being conducted in a cohort of patients with extensive-stage small cell lung cancer (ES-SCLC), large cell neuroendocrine carcinoma of the lung (LCNEC), or extrapulmonary neuroendocrine carcinomas (EP-NECs).

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As previously announced, Phanes is conducting this study under a clinical supply agreement with Roche. Peluntamig is Phanes’ first-in-class native IgG-like bispecific antibody (bsAb) targeting DLL3 and CD47. It was granted two orphan drug designations by the FDA for the treatment of SCLC and NEC, respectively, and two Fast Track designations for ES-SCLC with disease progression following platinum chemotherapy with or without a checkpoint inhibitor, and metastatic de novo or treatment-emergent neuroendocrine prostate cancer (NEPC), respectively.

The multi-center Phase I/II clinical trial of peluntamig (NCT05652686), known as the SKYBRIDGE study, is currently evaluating the safety, tolerability, pharmacokinetics and preliminary efficacy of peluntamig in patients with advanced or refractory cancers expressing DLL3. A Phase I clinical trial of peluntamig is also ongoing in China (CTR20242720), and a Phase II clinical trial has been approved in China.

TECENTRIQ (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group.

On May 5, 2025 CStone Pharmaceuticals ("CStone", HKEX: 2616), an innovation-driven biopharmaceutical company focused on anti-cancer therapies, reported that a poster presentation of preclinical data of CS2009 (PD-1/VEGF/CTLA-4 trispecific antibody), a key asset in CStone Pipeline 2.0, has been delivered at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, CStone Pharmaceauticals, MAY 5, 2025, View Source [SID1234652525]). CS2009 global phase I trial is ongoing in Australia with first patient dosed in this March and will soon be expanded to China and the US.

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PD-1, VEGFA, and CTLA-4 are clinically validated targets for immunotherapies, which can exert complementary, multi-dimensional anti-tumor effects through synergistic mechanisms. Blockade of PD-1 and CTLA-4 has demonstrated synergistic effects, extending overall survival benefits as well as progress-free survival benefits in many tumor types including NSCLC, which could be further strengthened by the blockade of VEGFA signaling. By integrating these three mechanisms of actions in one molecule, CS2009 holds great potential to deliver superior clinical benefits over PD-(L)1 antibodies or PD-(L)1/VEGF and PD-(L)1/CTLA4 bispecific antibodies.

CS2009 is a promising trispecific antibody targeting PD-1, VEGFA, and CTLA-4, which demonstrates broad clinical application prospects for solid tumors with the great potential to become the next-generation immune-oncology backbone to replace current anti-PD-(L)1-based therapies.

Key Highlights:

CS2009 exhibited enhanced affinity upon simultaneous PD-1/CTLA-4 engagement. CS2009 enhances anti-tumor efficacy by preferentially targeting PD-1/CTLA-4 double positive T cells in TME.
CS2009 exhibited an approximately 150-fold enhancement in checkpoint inhibitory activity on PD-1/CTLA-4 dual-reporter assay through crosslinking with VEGFA dimers. In PD-1 reporter assay, the CS2009/VEGFA combination demonstrated approximately 300-fold greater immune checkpoint activity compared to CS2009 alone. Mixed lymphocyte reaction (MLR) assays evaluating primary T cell activation revealed that crosslinking with VEGFA dimer significantly increases the activity of CS2009. These findings indicate enhanced activity of CS2009 in VEGFA-enriched TME and minimized peripheral overactivation-induced immune-related toxicity, thereby expanding its therapeutic window.
CS2009 demonstrated dose-dependent T-cell activation during GLP-toxicity study in cynomolgus monkeys.
CS2009 exhibited comparable pharmacokinetic (PK) profiles to those of monoclonal antibodies.
CS2009 demonstrates superb tolerability with the highest non-severely toxic dose (HNSTD)/ the no observed adverse effect level (NOAEL) identified as 100 mg/kg.
In summary, CS2009 is a trispecific antibody targeting PD-1, VEGFA, and CTLA-4, with the potential to be first- or best-in-class for major tumor types. Its differentiated molecular design combines three clinically validated targets, preferentially invigorating exhausted tumor infiltrating lymphocytes (TILs) while demonstrating VEGF neutralization comparable to existing anti-VEGF antibodies. CS2009 covers a wide range of cancers, including but not limited to non-small cell lung cancer, hepatocellular carcinoma, gastric adenocarcinoma, endometrial cancer, ovarian cancer, renal cell carcinoma, and cervical cancer. Our results show that CS2009 exhibits superior anti-tumor activity compared to potential competitors, including PD-(L)1/CTLA-4 bispecific antibodies, PD-(L)1/VEGF bispecific antibodies, and PD-(L)1/CTLA-4 combination therapies.

Poster Information:

Title: CS2009: A first-in-class trispecific antibody targeting PD-1, CTLA-4, and VEGFA with potential to be a next-generation backbone therapy with combined checkpoint inhibition and anti-angiogenesis
Session Title: Overcoming Checkpoint Inhibition and Tumor Suppression
Abstract Number: 7299
Date & Time: Wednesday, April 30, 2025, 9:00 AM – 12:00 PM ET
Location: Poster Section 39, Board #14

On May 5, 2025 AstraZeneca reported that Calquence (acalabrutinib) in combination with bendamustine and rituximab has been approved in the European Union (EU) for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are not eligible for autologous stem cell transplant (Press release, AstraZeneca, MAY 5, 2025, View Source [SID1234652524]).

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The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and was based on positive results from ECHO Phase III trial, presented at the European Haematology Association (EHA) (Free EHA Whitepaper) 2024 Congress and published in The Journal of Clinical Oncology, which demonstrated that 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 progression-free survival (PFS) was 66.4 months for patients treated with the Calquence combination versus 49.6 with chemoimmunotherapy alone.

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma, often diagnosed at an advanced stage.1,2 An estimated 6,000 patients were diagnosed with MCL in the UK, France, Germany, Spain and Italy in 2024.3

Martin Dreyling, MD, Department of Medicine, University Hospital LMU Munich, and investigator in the trial, said: "This approval provides a new first-line treatment option for patients in the EU with mantle cell lymphoma, an aggressive lymphoma with a dismal long-term outcome still today. With a progression-free survival improvement of more than 16 months for these patients, the acalabrutinib combination is a much-needed advance in this challenging disease."

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: "Treatment with the Calquence combination in first-line mantle cell lymphoma demonstrated a significant improvement in progression free survival and a consistent safety profile for patients in the pivotal ECHO trial. As the first and only BTK inhibitor approved in this indication in the EU, we are proud to provide a much-needed new option to patients living with this difficult disease."

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

Calquence plus bendamustine and rituximab is approved in the US and several other countries in this setting based on the ECHO results. Regulatory applications are currently under review in Japan and several other countries in this indication.

This approval follows the recent approval for Calquence monotherapy for the treatment of adult patients with relapsed or refractory MCL in the EU.

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; 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.3,4,5

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 overall survival (OS), overall response rate, duration of response and time to response.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.

Calquence
Calquence is a second-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.7 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.

Calquence is approved for the treatment of chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) in the US, Japan and China, and approved for CLL in the EU and many other countries. Calquence is also approved for the treatment of adult patients with previously untreated MCL in the US and other countries. It is also approved for the treatment of adult patients with MCL who have received at least one prior therapy in China and several other countries. Calquence is not currently approved for the treatment of MCL in Japan.

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.

AstraZeneca in haematology
AstraZeneca is pushing the boundaries of science to redefine care in haematology. Our goal is to help transform the lives of patients living with malignant, rare and other related haematologic diseases through innovative medicines and approaches that are shaped by insights from patients, caregivers and physicians.

In addition to our marketed products, we are spearheading the development of novel therapies designed to target underlying drivers of disease across multiple scientific platforms. Our acquisitions of Alexion, with expertise in rare, non-malignant blood disorders, and Gracell Biotechnologies Inc., pioneers of autologous cell therapies, expand our haematology pipeline and enable us to reach more patients with high unmet needs through the end-to-end discovery, development and delivery of novel therapies.

On May 5, 2025 Halozyme Therapeutics, Inc. (NASDAQ: HALO) ("Halozyme") reported that Dr. Helen Torley, president and chief executive officer, will present and host investor meetings at the BofA Securities 2025 Healthcare Conference (Press release, Halozyme, MAY 5, 2025, View Source [SID1234652523]).

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The presentation is scheduled for Tuesday, May 13 at 4:20pm PT / 7:20pm ET.

A live audio webcast will be available on the Investor Relations section of the Company’s website. Replays of the audio webcasts will be available for 90 days following the conference.

On May 5, 2025 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a late-stage immunotherapy company targeting cancer and autoimmune diseases, reported an excellent median Overall Survival (OS) of 17.6 months has been achieved in Cohort B of the TACTI-003 (KEYNOTE-C34) Phase IIb trial (Press release, Immutep, MAY 5, 2025, View Source [SID1234652522]). This part of the Phase II study evaluates eftilagimod alfa (efti) in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab) as first line therapy in recurrent/metastatic head and neck squamous cell carcinoma (1L HNSCC) patients with PD-L1 expression below 1 (Combined Positive Score [CPS] <1).

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The mature 17.6-months median OS in evaluable patients (N=31) with a data cut-off of 31 March 2025 compares favourably to historical results from the two current standard-of-care approaches for 1L HNSCC patients with CPS <1 including 10.7-months from cetuximab + chemotherapy and 11.3-months from anti-PD-1 therapy + chemotherapy, as well as 7.9-months from anti-PD-1 monotherapy.1,2

Patients with CPS <1 in 1L HNSCC represent a treatment population with high unmet medical need. Up to 20% of 1L HNSCC patients have CPS <1 and despite immunotherapy’s progress in fighting cancer, anti-PD-1 therapy alone (without chemotherapy) is only approved for patients who express PD-L1 (CPS >1). Additionally, all available treatment options for patients with PD-L1 CPS <1 include chemotherapy.

Importantly, efti in combination with pembrolizumab continues to be well-tolerated with no new safety signals. This safety and mature OS data build on the encouraging high overall response rate with multiple complete responses achieved through combining these powerful immunotherapies in 1L HNSCC patients with CPS <1.3

"We are excited to see this strong survival benefit for head and neck cancer patients with such cold tumors. Combining these two complementary immunotherapies has led to a 7-fold increase in response rates and a more than doubling of median overall survival as compared to historical results from anti-PD-1 monotherapy. Driving durable responses that translate into clinically meaningful survival holds tremendous promise for these patients in need of more tolerable and efficacious therapies," said Marc Voigt, CEO of Immutep.

"There is a high unmet need in 1L HNSCC patients with cold tumors and PD-L1 CPS <1, due to the lack of an approved immunotherapy-only treatment regimen and a lack of competitor trials with chemotherapy-free approaches targeting this patient population. Given the strength of the efficacy and safety results generated to date with efti in combination with pembrolizumab, we will meet with regulators to discuss next steps and potential paths to approval," added Mr. Voigt.

Next Steps
Efti has Fast Track designation in 1L HNSCC and Immutep has requested a meeting with the U.S. Food and Drug Administration (FDA) to discuss next steps including potential paths to approval for 1L HNSCC with PD-L1 CPS <1. Patient follow up, data collection, cleaning and analysis continue for TACTI-003, and the Company plans to provide a further update later this year.

About Eftilagimod Alfa (efti)
Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track designation in first line HNSCC and in first line NSCLC from the United States Food and Drug Administration (FDA).