On March 7, 2025 Astrazeneca reported positive high-level results from the MATTERHORN Phase III trial showed perioperative treatment with AstraZeneca’s Imfinzi (durvalumab) in combination with standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival (EFS) (Press release, AstraZeneca, MAR 7, 2025, View Source [SID1234650995]). Patients were treated with neoadjuvant Imfinzi in combination with chemotherapy before surgery, followed by adjuvant Imfinzi in combination with chemotherapy, then Imfinzi monotherapy. The trial evaluated this regimen versus perioperative chemotherapy alone for patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers.

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For the secondary endpoint of overall survival (OS), a strong trend was observed in favour of the Imfinzi-based regimen at this interim analysis. The trial will continue to follow OS, which will be formally assessed at the final analysis.

Gastric cancer is the fifth leading cause of cancer death globally, with nearly one million people diagnosed each year.1 In 2024, there were roughly 43,000 drug-treated patients in the US, European Union (EU) and Japan in early-stage and locally advanced gastric or GEJ cancer.2 Approximately 62,000 patients in these regions are expected to be newly diagnosed in this setting by 2030.3

Yelena Y Janjigian, MD, Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York and principal investigator in the trial, said: "Despite receiving curative-intent chemotherapy and surgery, patients with gastric cancer commonly face disease recurrence and have a poor prognosis. These exciting data from MATTERHORN show that a durvalumab-based perioperative regimen resulted in a clinically meaningful improvement in patient outcomes, including decreasing the risk of the cancer coming back."

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: "MATTERHORN is the first Phase III trial of an immunotherapy to show a statistically significant improvement in event-free survival in patients with resectable gastric and gastroesophageal junction cancers. This perioperative approach with Imfinzi underscores our commitment to moving into earlier stages of cancer where novel therapies can have the biggest impact on patients’ lives."

The safety profile for Imfinzi and FLOT chemotherapy was consistent with the known profiles of each medicine, and there were no new safety findings.

In a previously reported interim analysis for the key secondary endpoint of pathologic complete response (pCR), the Imfinzi combination more than doubled the pCR rate compared to neoadjuvant chemotherapy alone (19% versus 7%, odds ratio 3.08; p<0.00001).4

Data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.

Notes
Gastric and gastroesophageal junction cancers

Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth-highest leading cause of cancer mortality.1 In many regions, its incidence has been increasing in patients younger than 50 years old, along with other gastrointestinal (GI) malignancies.5 Nearly one million new patients were diagnosed with gastric cancer in 2022, with approximately 660,000 deaths reported globally.1

GEJ cancer is a type of gastric cancer that arises from and spans the area where the oesophagus connects to the stomach.6

Disease recurrence is common in patients with resectable gastric cancer despite undergoing surgery with curative intent and treatment with neoadjuvant/adjuvant chemotherapy. Approximately one in four patients with gastric cancer who undergo surgery develop recurrent disease within one year, and one in four patients do not survive beyond two years, reflecting high unmet medical need.7-8 Additionally, the five-year survival rate remains poor, with less than half of patients alive at five years.9

MATTERHORN
MATTERHORN is a randomised, double-blind, placebo-controlled, multi-centre, global Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage II-IVA gastric and GEJ cancers. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, 948 patients were randomised to receive a 1500mg fixed dose of Imfinzi plus FLOT chemotherapy or placebo plus FLOT chemotherapy every four weeks for two cycles prior to surgery. This was followed by Imfinzi or placebo every four weeks for up to 12 cycles after surgery (including two cycles of Imfinzi or placebo plus FLOT chemotherapy and 10 additional cycles of Imfinzi or placebo monotherapy).

In the MATTERHORN trial, the primary endpoint is EFS, defined as the time from randomisation until progression that precludes surgery or requires non-protocol therapy, local or distant recurrence or progression of disease, or death due to any cause as assessed by blinded independent central review (BICR) according to RECIST 1.1 and/or local pathology testing. Key secondary endpoints include pCR rate, defined as the proportion of patients who have no detectable cancer cells in resected tumour tissue following neoadjuvant therapy, and OS. The trial enrolled participants in 176 centres in 20 countries, including in the US, Canada, Europe, South America and Asia.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer (BTC) and in combination with Imjudo (tremelimumab) in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU.

In addition to its indications in GI cancers, Imfinzi is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, Imfinzi is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable non-small cell lung cancer (NSCLC), and in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC. Imfinzi is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy (etoposide and either carboplatin or cisplatin) for the treatment of extensive-stage SCLC.

Imfinzi in combination with chemotherapy followed by Imfinzi monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in US and EU). Imfinzi in combination with chemotherapy followed by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in EU and Japan.

Since the first approval in May 2017, more than 374,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several GI and gynaecologic cancers, and other solid tumours.

On March 6, 2025 CStone Pharmaceuticals (stock code: 2616.HK), an innovation-driven biopharmaceutical company focused on developing oncology drugs, reported the successful submission of a Phase Ib clinical trial application in Australia for CS5001 (ROR1 ADC), a key product in its 2.0 pipeline, in combination with standard-of-care therapy, in first-line diffuse large B-cell lymphoma (DLBCL) (Press release, CStone Pharmaceauticals, MAR 6, 2025, View Source [SID1234656220]). Additionally, a global, multi-center clinical trial evaluating CS5001 alone and in combination with a PD-L1 monoclonal antibody for the treatment of advanced solid tumors is also underway.

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This Phase Ib clinical trial further expands upon the previous studies of CS5001 monotherapy in patients with advanced, aggressive, and indolent lymphomas. It aims to further explore the clinical application value of CS5001 across the full spectrum of DLBCL disease and continue to expand its scope in solid tumor treatment. The trial expansion includes:

• In combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) for the treatment of patients with DLBCL who have not received prior systemic therapy;

• Combination with standard therapy for patients with relapsed or refractory DLBCL;

• Monotherapy for patients with ROR1-positive advanced solid tumors;

• Combined with sugemalimab for the treatment of patients with advanced solid tumors.

Dr. Jianxin Yang, CEO, President of R&D, and Executive Director of CStone Pharmaceuticals, said, "We are very pleased to see this important progress in the clinical development of CS5001 (ROR1 ADC). Existing data have demonstrated that CS5001 exhibits broad potential in both solid tumors and lymphomas. In a Phase II clinical study, the ROR1 ADC combined with R-CHP achieved impressive complete response (CR) rates in first-line DLBCL. With the expansion of our Phase Ib clinical trial from late-line monotherapy to combination therapy in the frontline setting, CS5001 has the potential to bring groundbreaking therapeutic benefits to patients with DLBCL and reshape the standard of care for this disease. Furthermore, as the first ROR1 ADC with demonstrated clinical anti-tumor activity in both solid tumors and lymphomas, we are actively advancing the development of CS5001 in solid tumors and look forward to its subsequent clinical success."

Currently, a global, multicenter Phase Ib clinical trial of CS5001 is progressing simultaneously in the United States, Australia, and China. Enrollment is underway in the monotherapy cohort for both aggressive and indolent advanced lymphomas, with the goal of subsequently expanding into a Phase II, single-arm, registrational study. Enrollment is also expected to commence in combination with CS5001 for first-line or relapsed/refractory DLBCL, as well as in the monotherapy and combination treatment of advanced solid tumors.

About the CS5001 (ROR1 ADC)

CS5001 is an antibody-drug conjugate (ADC) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1). This drug utilizes a unique design, combining a tumor-specifically activated pyrrolobenzodiazepine (PBD) protoxin payload and a linker. CS5001 is internalized by tumor cells only after reaching them. Within lysosomes, the linker is cleaved by a specific enzyme highly expressed in tumor cells, releasing the PBD protoxin. The PBD protoxin is then activated within the tumor cells, leading to precise cell killing. This "dual-control" mechanism of linker plus protoxin effectively mitigates the toxicity issues associated with traditional PBD payloads and significantly extends the safety window. CS5001 has demonstrated complete tumor suppression in multiple preclinical cancer models, along with favorable serum half-life and pharmacokinetic properties, demonstrating its significant clinical development potential and broad application prospects in the treatment of various solid and hematological tumors. In addition, CS5001 uses directed coupling technology to achieve a precise drug-antibody ratio (DAR), providing strong guarantees for homogeneous production and large-scale production.

In October 2020, CStone Pharmaceuticals and LigaChem Biosciences, Inc. (LCB) entered into a licensing agreement for the development and commercialization of CS5001. CS5001 was originally co-synthesized by LCB and ABL bio, two leading Korean biotech companies. Under the terms of the agreement, CStone Pharmaceuticals obtained exclusive development and commercialization rights for CS5001 worldwide, excluding Korea.

At the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, first-in-human data from a CS5001 study in patients with advanced solid tumors and lymphomas were presented as a poster. Subsequently, at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, updated clinical data on CS5001 as a monotherapy for advanced lymphomas were also presented.

CS5001 demonstrated a favorable safety profile and significant anti-tumor activity across 10 dose cohorts in a Phase 1a dose-escalation trial:

• At the initially selected Phase II recommended dose (RP2D) level (125 μg/kg), CS5001 achieved an objective response rate (ORR) of 70% and 100% for advanced B-cell non-Hodgkin lymphoma and Hodgkin lymphoma, respectively;

• Significant efficacy signals for CS5001 were observed in advanced solid tumors such as pancreatic cancer, ovarian cancer, non-small cell lung cancer, and triple-negative breast cancer;

• CS5001 showed good tolerability in patients with multi-line-treated advanced B-cell lymphoma and solid tumors.

On March 6, 2025 The board (the "Board") of directors ("Directors", and each a "Director") of the Company reported that the Group has received approval from the National Medical Products Administration of the People’s Republic of China (the "NMPA") for a clinical trial of IMM01 (Timdarpacept) in combination with IMM2510 (palverafusp α) and with or without chemotherapy, for the treatment of advanced malignant tumors (Press release, ImmuneOnco Biopharma, MAR 6, 2025, View Source [SID1234655708]). This significant progress marks another key step in the Company’s rapid advancement of clinical research of IMM01 (Timdarpacept) and IMM2510 (palverafusp α).

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ABOUT IMM01 (TIMDARPACEPT)
IMM01 (Timdarpacept), the Group’s core product, is an innovative molecule targeting CD47. It is the first SIRPα-Fc fusion protein to enter into clinical stage in China. IMM01 (Timdarpacept) designed with immunoglobulin G1 (IgG1) Fc can fully activate macrophages via a dual mechanism — simultaneously blocking the "don’t eat me" signal by disrupting CD47/SIRPα interaction and delivering the "eat me" signal through the engagement of activating Fc-gamma (Fcγ) receptors on macrophages. Furthermore, the CD47-binding domain of IMM01 (Timdarpacept) was specifically engineered to avoid human red blood cell (RBC) binding. With the differentiated molecule design, IMM01 (Timdarpacept) has achieved a favorable safety profile and demonstrated its ability to activate macrophages. IMM01 (Timdarpacept) in combination with azacitidine was granted orphan-drug designation by the Food and Drug Administration of the United States (FDA) for the first-line treatment of CMML in November 2023. The Group owns the global intellectual property rights and commercial rights of IMM01 (Timdarpacept). As of the date of this announcement, in relation to IMM01 (Timdarpacept), the Group owned one patent family, which includes issued patents in China, the United States, Japan and the European Union.

ABOUT IMM2510 (PALVERAFUSP α)
IMM2510 (palverafusp α), independently developed by the Group, is a bispecific molecule with a mAb-Trap structure targeting vascular endothelial growth factor (VEGF) and programmed cell death ligand 1 (PD-L1). IMM2510 (palverafusp α) can inhibit angiogenesis, leading to tumor shrinkage, and sensitize tumor cells to immune responses, while activating T cells, NK cells, and macrophages via the blockade of PD-L1/programmed cell death protein 1 (PD-1) interaction and the induction of Fc-mediated antibody-dependent cellular cytotoxicity (ADCC)/antibody-dependent cellular phagocytosis (ADCP) activity. The Company and Axion Bio, Inc. (formerly known as SynBioTx Inc.), a wholly-owned subsidiary of Instil Bio, Inc. (NASDAQ: TIL), have entered into a license and collaboration agreement, pursuant to which the Company owns the commercial rights of IMM2510 (palverafusp α) in the Greater China region, including mainland China, Hong Kong Special Administrative Region of China, Macau Special Administrative Region of China and Taiwan (the "Greater China Region") and agreed to grant Axion Bio, Inc. an exclusive license to research, develop and commercialize IMM2510 (palverafusp α), outside the Greater China region.

On March 6, 2025 Merck, a leading science and technology company, reported profitable growth in 2024 and delivered on its guidance for the year (Press release, Merck KGaA, MAR 6, 2025, View Source [SID1234654166]). A strong performance of Healthcare, a rebound in Life Science and profitable growth in Electronics contributed to this. During the year, Merck also strategically sharpened its portfolio’s focus on future growth areas. After a strong fourth quarter 2024, the company is looking toward 2025 with confidence and expects continued profitable growth.

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"Merck is back on a growth path with all three businesses. The challenges of recent years have been taken as an opportunity to strengthen our supply chains and invest in Europe, the United States and Asia. In 2025, we will continue to deliver profitable growth across our company. With our innovation-driven portfolio, we are ideally positioned to benefit from global macro trends such as complex biologics, novel modalities, and semiconductors for the AI era," said Belén Garijo, Chair of the Executive Board and CEO of Merck.

On March 6, 2025, Bio-Path Holdings, Inc. (the "Company") reported to have entered into a securities purchase agreement (the "Purchase Agreement") with 1800 Diagonal Lending LLC, a Virginia limited liability company (the "Lender"), an accredited investor, for the issuance and sale of a promissory note in the aggregate principal amount of $161,000 (the "Note") for a purchase price of $140,000 after deducting the original issue discount of $21,000 (Filing, Bio-Path Holdings, MAR 6, 2025, View Source [SID1234651019]). The Note bears a one-time interest charge of twelve percent that is applied on the date of issuance, March 6, 2025. The Note shall be paid in five payments with the first payment of $90,160 due on August 30, 2025 and each subsequent payment shall be equal to $22,540 which are due on September 30, 2025, October 30, 2025, November 30, 2025 and December 30, 2025.

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Upon the occurrence and during any continuation of any Event of Default (as defined in the Note), the Note shall become immediately due and payable and the Company shall pay to the Lender, in full satisfaction, an amount equal to 150% times the sum of (i) the then outstanding principal amount of the Note plus (ii) accrued and unpaid interest on the unpaid principal amount of the Note to the date of payment plus (iii) default interest, if any, at a rate of 22% per annum on the amounts referred to in clauses (i) and/or (ii) plus (iv) any amounts owed to the Lender pursuant to the Conversion Right (as defined below). In addition, only upon an Event of Default and during any continuation thereof, the Lender may elect to convert all or any part of the outstanding principal and interest on the Note in fully paid and non-assessable shares of the Company’s common stock, par value $0.001 per share ("Common Stock") at a conversion price per share equal to 65% of the lowest closing bid price of the Common Stock for the ten trading days prior to the date of conversion (the "Conversion Right"). The Lender, together with its affiliates, may not convert any portion of such Note to the extent that the Lender would own more than 4.99% of the Company’s outstanding Common Stock immediately after the conversion

The issuance of the Note and the issuance of the shares of Common Stock issuable upon any Event of Default will not be registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state securities laws. The Note and the shares of Common Stock, if issued, will be issued in reliance on the exemptions from registration provided by Section 4(a)(2) under the Securities Act and/or Regulation D promulgated thereunder.

The Note and the Purchase Agreement contain standard and customary representations and warranties, agreements and obligations, and events of default. The foregoing descriptions of terms and conditions of the Purchase Agreement and the Note do not purport to be complete and are qualified in their entirety by the full text of the form of the Purchase Agreement and the Note, which are attached hereto as Exhibits 10.1 and 4.1, respectively.

This Current Report on Form 8-K does not constitute an offer to sell the securities or a solicitation of an offer to buy the securities, nor shall there be any sale of the securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.