On April 25, 2025 Shanghai Junshi Biosciences Co., Ltd (Junshi Biosciences, HKEX: 1877; SSE: 688180), a leading innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies, reported that the supplemental new drug application ("NDA") for toripalimab (trade name: TUOYI) as the first-line treatment for unresectable or metastatic melanoma has been approved by the National Medical Products Administration ("NMPA") (Press release, Shanghai Junshi Bioscience, APR 25, 2025, View Source [SID1234656129]). This marks the approval of toripalimab’s 12th indication in the Chinese mainland.

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Melanoma is the most malignant type of skin cancer. According to GLOBOCAN 2022 statistics, approximately 332,000 new melanoma cases and 59,000 deaths were recorded globally that year. Though melanoma is relatively uncommon in China, its mortality rate is high (approximately 5,000 deaths amongst approximately 9,000 new cases in 2022) and its incidence rate is rising year by year. Since 2018, anti-PD-1 monoclonal antibodies have been approved for the second-line or later treatment of advanced melanoma in China and are widely used clinically. However, the first-line standard treatment for advanced melanoma is still dominated by traditional chemotherapy or targeted therapy (limited to patients with BRAF V600 mutation). Until now, no domestic anti-PD-1 monoclonal antibody had been approved for advanced melanoma in China, creating an urgent clinical need for first-line immunotherapy options.

The supplemental NDA approval is based on data from the MELATORCH study (NCT03430297). MELATORCH is a multicenter, randomized, open-label, positive-controlled Phase 3 clinical study, and is also the first pivotal registrational clinical study of a PD-(L)1 inhibitor as the first-line treatment for advanced melanoma that has yielded positive results. Led by Professor Jun GUO from Peking University Cancer Hospital as the Principal Investigator, the study was conducted in 11 clinical centers across the country. The study was designed to compare the efficacy and safety of toripalimab versus dacarbazine for the systemic anti-tumor treatment-naive patients with unresectable or metastatic melanoma.

Prior to this, the results of the MELATORCH study made its debut at the 27th National Clinical Oncology Conference and 2024 Chinese Society of Clinical Oncology (CSCO) Annual Meeting. The results showed that compared with the dacarbazine group (N=128), the progression-free survival ("PFS") assessed by Blinded Independent Central Review (BICR) of the toripalimab group (N=127) was significantly prolonged, with the median PFS of the two groups being 2.3 months vs. 2.1 months respectively, and the disease progression or mortality risk was reduced by 29.2% (hazard ratio [HR]=0.708, 95% CI: 0.526-0.954; P=0.0209). The sensitivity analysis of median overall survival ("OS"), corrected for the impact of subsequent anti-tumor treatment, showed that compared with the dacarbazine group, the toripalimab treatment group showed a significant trend towards survival benefit, with the median OS being 15.1 months vs. 9.4 months (HR=0.680, 95% CI: 0.486-0.951) respectively. Toripalimab has a good safety profile that is consistent with previous studies with no new safety signals identified.

Professor Jun GUO from Peking University Cancer Hospital said, "Melanoma is a highly aggressive cancer. Due to its low sensitivity to traditional radiotherapy and chemotherapy, patients are often faced with poor survival outcomes. However, thanks to melanoma’s high immunogenicity, immunotherapies such as toripalimab have significantly improved patient survival in recent years. In China, advanced melanoma patients—including those in second-line and later—have gained broad access to these treatments through national medical insurance. Now, toripalimab has been extended to first-line treatment of advanced melanoma. Compared to traditional chemotherapy, toripalimab has demonstrated significant advantages in PFS, ORR, and DoR, as well as a clear trend toward improved OS. Notably, this approval was based on the MELATORCH study, which exclusively enrolled Chinese patients. The trial design aligned closely with clinical practice in China, and thus the findings were more relevant to Chinese melanoma patients. We hope that China’s independently developed immunotherapies like toripalimab can provide a comprehensive treatment solution for advanced melanoma and offer new hope to more patients."

Dr. Jianjun ZOU, General Manager and CEO of Junshi Biosciences, also shared her enthusiasm: "Within a month, toripalimab has secured approvals for two new indications—liver cancer and melanoma. This milestone achievement was, without a doubt, made possible by the selfless and dedicated collaboration of researchers, participating patients, and R&D teams. Seven years ago, toripalimab had just pioneered breakthroughs in second-line melanoma treatment, becoming China’s first domestically developed anti-PD-1 monoclonal antibody and starting a new era of immunotherapy in China; today, toripalimab is again reaching new heights as it becomes the first Chinese-developed first-line immunotherapy for melanoma. Not only does this demonstrate toripalimab’s exceptional clinical value, it also reflects China’s growing strength and innovation in immuno-oncology. Moving forward, we will remain committed to advancing world-class therapies to benefit patients across the world!"

On April 25, 2025 ALX Oncology Holdings Inc., ("ALX Oncology" or the "Company") (Nasdaq: ALXO), a clinical-stage biotechnology company advancing a pipeline of novel therapies designed to treat cancer and extend patients’ lives, reported topline data from its Phase 2 ASPEN-03 and ASPEN-04 clinical trials (Press release, ALX Oncology, APR 25, 2025, View Source [SID1234652135]). The company’s investigational CD47-blocker evorpacept, when added to Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab) with or without chemotherapy, did not meet the primary endpoints in the ASPEN-03 and ASPEN-04 trials of improved objective response rates (ORR) as compared to historical controls of pembrolizumab alone and pembrolizumab with chemotherapy, respectively, as a first-line treatment in patients with advanced head and neck squamous cell carcinoma (HNSCC). The combination of evorpacept and pembrolizumab with or without chemotherapy in ASPEN-03 and ASPEN-04 demonstrated a manageable safety profile and was consistent with what has been previously reported for pembrolizumab and chemotherapy in this setting. Although the company will no longer pursue evorpacept in combination with pembrolizumab in HNSCC, multiple clinical trials of evorpacept in combination with anti-cancer antibodies will continue based on established proof-of-concept.

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Evorpacept blocks the ‘don’t eat me’ signal transmitted by CD47 on the surface of cancer cells that these cells use to evade detection by the immune system. As its primary mechanism of action, evorpacept is uniquely designed to stimulate macrophages to selectively attack cancer cells and not healthy cells, when combined with active anti-cancer antibodies. This mechanism has translated into durable clinical responses and a well-tolerated safety profile in HER2-positive gastric and HER2-positive breast cancer clinical trials. To further explore the benefit in this setting, evorpacept is currently being evaluated in combination with various anti-cancer antibodies in colorectal cancer, breast cancer, non-Hodgkin lymphoma and multiple myeloma.

In the ASPEN-03 and ASPEN-04 clinical trials, evorpacept was combined with pembrolizumab with or without chemotherapy to investigate a second and distinct mechanism of action. This discrete approach explored the concept that evorpacept may enhance T-cell priming by activating dendritic cells and stimulating the adaptive immune system. The trial outcomes were not sufficiently supportive of advancing evorpacept in combination with pembrolizumab in HNSCC into a registrational trial.

"While there were encouraging trends in ASPEN-03 in ORR versus the historical and internal control, we’ve decided not to pursue evorpacept and pembrolizumab in head and neck cancer in light of our prioritization of the more established anti-cancer antibody combination program based on multiple positive studies," said Alan Sandler, M.D., Chief Medical Officer at ALX Oncology. "We are disappointed that these studies did not meet their primary endpoints, most importantly for the patients for whom current standard-of-care treatment approaches fall short, and we thank all who participated in the trials."

"Moving forward, we are continuing to rapidly advance our clinical program combining evorpacept with anti-cancer antibodies supported by robust clinical data across trials in multiple tumor types. Evorpacept has demonstrated response rates and durability beyond what is expected from standard of care across several studies when combined with HERCEPTIN, zanidatamab and RITUXAN," said Jason Lettmann, Chief Executive Officer at ALX Oncology. "Based on the positive data and strong mechanistic rationale, we maintain our confidence in the evorpacept clinical development program and intend to deliver on that promise with additional clinical data in breast cancer and colorectal cancer in the near-term. With evorpacept and ALX2004, our novel EGFR-targeted antibody-drug conjugate, we continue our commitment to bringing forth meaningful therapies for patients living with cancer."

Detailed findings from the ASPEN-03 and ASPEN-04 trials will be submitted to a future medical meeting.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About ASPEN-03 and ASPEN-04 Clinical Trials
ASPEN-03 and ASPEN-04 are randomized, multi-center, international Phase 2 trials evaluating evorpacept, ALX Oncology’s investigational CD47-blocking therapeutic that uniquely combines a high-affinity CD47-binding domain with an inactivated proprietary Fc domain, in patients with metastatic or unresectable, recurrent HNSCC who have not yet been treated for their advanced disease. The ASPEN-03 trial (NCT04675294) is evaluating evorpacept in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) against pembrolizumab alone for the treatment of patients whose HNSCC is PD-L1 positive. The ASPEN-04 trial (NCT04675333) is evaluating evorpacept in combination with pembrolizumab and chemotherapy against pembrolizumab and chemotherapy alone in patients with HNSCC, regardless of PD-L1 status. Patient characteristics in the trials (N=346) were generally well-balanced across arms. The primary endpoints for the ASPEN-03 and ASPEN-04 trials is ORR compared to historical control. Key secondary endpoints for both trials are safety, duration of response (DOR), progression-free survival (PFS) and overall survival (OS).

About Head and Neck Squamous Cell Carcinoma (HNSCC)
HNSCC is a serious and life-threatening disease that originates in the squamous cells lining the mucosal surfaces of the head and neck, including the mouth, throat, voice box, sinuses and nasal cavity. HNSCC is the seventh most common cancer worldwide and the incidence of HNSCC is expected to increase 30% by 2030. Despite current standard-of-care therapies and recent advancements in diagnosis and treatment, people with HNSCC face a poor prognosis, particularly when diagnosed at advanced stages. Further, the survival rate for HNSCC has only modestly improved in recent years, even with the availability of new treatment modalities, underscoring a need for improved therapeutics.

About Evorpacept
ALX Oncology’s lead therapeutic candidate, evorpacept, is a highly differentiated potential best- and first-in-class CD47 checkpoint inhibitor and one of the most advanced checkpoint inhibitors to target and activate the innate immune system. Evorpacept was intentionally designed to maximize the clinical potential of blocking CD47, while reducing the toxicities associated with previous approaches to CD47 blockade. In clinical studies across a wide spectrum of tumor types in more than 700 patients to date, evorpacept has demonstrated potential to enhance the therapeutic activity of many of the most important cancer therapies available today, contributing an additional, differentiated immuno-oncology mechanism. Based on this potential, ALX Oncology is advancing a robust clinical program evaluating evorpacept in a wide range of cancer indications, prioritizing its combination with anti-cancer antibodies in breast, gastric and colon cancers. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to evorpacept for the second-line treatment of patients with HER2-positive gastric or GEJ carcinoma. Additionally, both the FDA and European Commission have granted Orphan Drug Designation for this indication.

On April 25, 2025 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, reported that it has entered into a securities purchase agreement with certain institutional and accredited investors for a private placement of approximately $24 million of shares of its common stock at a price of $7.00 per share and, in lieu of common stock to certain investors, $51 million of pre-funded warrants to purchase shares of its common stock at a price of $6.9999 per pre-funded warrant (Press release, Verastem, APR 25, 2025, View Source [SID1234652151]). The exercise price of each pre-funded warrant will equal $0.0001 per share. Verastem expects to receive gross proceeds from the offering of approximately $75 million, before deducting placement agent fees and other offering expenses.

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The private placement was led by RTW Investments, with participation from other new and existing investors, including BVF Partners, Nantahala Capital, Octagon Capital, OrbiMed and Stonepine Capital Management.

The private placement is expected to close on or about April 28, 2025, subject to the satisfaction of customary closing conditions.

Proceeds from the financing are expected to fund the potential launch of avutometinib and defactinib in recurrent low-grade serous ovarian cancer, continued clinical research and development of product candidates including VS-7375, and for working capital and other general corporate purposes.

Guggenheim Securities is acting as the lead placement agent for the private placement. RBC Capital Markets, BTIG, Mizuho and B. Riley Securities are acting as co-placement agents for the private placement (together with Guggenheim Securities, the "Placement Agents"). The Company has agreed to pay customary placement fees and reimburse certain expenses of the Placement Agents.

The securities to be sold in the private placement have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state or other applicable jurisdictions’ securities laws, and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Securities Act and applicable state or other jurisdictions’ securities laws. Verastem has agreed to file a registration statement with the United States Securities and Exchange Commission (the "SEC") registering the resale of the shares of common stock issued in the private placement and the shares of common stock issuable upon the exercise of the pre-funded warrants issued in the private placement, no later than 30 days after the closing of the private placement.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any offer, solicitation or sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful. Any offering of the securities under the resale registration statement will only be made by means of a prospectus.

On April 25, 2025 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported that it will present new data from studies evaluating two of its internally developed, next-generation, investigational oncology therapies that it has global rights to, ZL-6201, a novel leucine-rich repeat-containing protein 15 (LRRC15) antibody-drug conjugate (ADC) targeting multiple solid tumors, and ZL-1222, an innovative anti-PD-1/ interleukin-12 (IL-12) immunocytokine for cancer immunotherapy, during poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago, Illinois this week (Press release, Zai Laboratory, APR 25, 2025, View Source [SID1234652168]). The data provide strong evidence supporting continued evaluation of both investigational therapies.

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"The latest findings that will be presented at AACR (Free AACR Whitepaper) 2025 demonstrate impressive potential for the continued advancement of these next-generation oncology therapies," said Linda Liu, Ph.D., Senior Vice President, Biologics Discovery, Zai Lab. "We look forward to continuing our evaluation of these therapies that may provide the opportunity to broaden treatment options for patients who have been unresponsive or resistant to current treatments across a broad range of cancer types."

ZL-6201 is a potential first- and best-in-class ADC with high affinity and specificity for LRRC15, an appealing target for cancer therapy due to its overexpression in multiple solid tumor types such as sarcoma, glioblastoma and melanoma. The compound was designed with a novel ADC technology platform called TMALIN, which leverages the tumor microenvironment to overcome challenges associated with first-generation ADC therapies, including off-target payload toxicity.

Findings to be presented at AACR (Free AACR Whitepaper) 2025 on Tuesday, April 29, demonstrate that ZL-6201 efficiently internalizes within and kills tumor cells, while also exhibiting a strong bystander killing effect in the tumor microenvironment where the target is often expressed. In multiple in vitro and in vivo pre-clinical studies, treatment with ZL-6201 effectively suppressed the growth of established tumors. Based on these findings, Zai Lab plans to initiate Investigational New Drug (IND)-enabling studies of ZL-6201 as a potential treatment for patients with sarcoma and other LRRC15-positive solid tumors, such as breast cancer and other malignancies, in 2025.

ZL-1222 is a PD-1 targeted, next-generation IL-12 immunocytokine designed to leverage the anti-tumor potential of IL-12 while lowering the associated systemic toxicity. Previous preclinical studies have demonstrated that IL-12 can have dramatic anti-tumor activity. However, in clinical investigations, systemic administration of IL-12 has been associated with a narrow therapeutic index with severe adverse events.

Findings from preclinical studies to be presented Monday, April 28, at AACR (Free AACR Whitepaper) 2025 suggest that ZL-1222, through precisely tailored IL-12 activity and PD-1 targeting, demonstrate potent anti-tumor activity in both anti-PD-1 sensitive and resistant tumor models, with improved systemic safety. These results indicate its potential to benefit patients who are unresponsive or resistant to the current immuno-oncology therapies.

"At Zai Lab we are building a robust portfolio of potential first- and best-in-class oncology therapies to expand treatment options for patients around the world," said Rafael G. Amado, M.D., President, Head of Global Research and Development, Zai Lab. "Findings from our preclinical studies of ZL-6201 and ZL-1222 demonstrate our commitment to identifying innovative approaches that address limitations associated with first-generation therapies. These include the ability to deliver higher concentrations of cytotoxic agents and limit off-target toxicity, in order to deliver meaningful treatment options for patients with a range of cancer types."

Details regarding the Zai Lab poster presentations at AACR (Free AACR Whitepaper) 2025 are as follows:

Title: Discovery and characterization of a novel LRRC15-targeting antibody-drug conjugate (ADC) for the treatment of solid tumors
Presenter: Bing Wan, Ph.D., Executive Director, Biology, Zai Lab
Session Title: New and Emerging Cancer Drug Targets
Date/Time: Tuesday, April 29, 2025, from 9:00 a.m. – 12:00 p.m. CT
Location: McCormick Place Convention Center, Poster Section 17
Poster Board Number: 23
Published Abstract Number: 4266

Title: Cis-delivery of a potency-reduced IL-12 via an anti-PD-1 single-chain antibody exhibits potent anti-tumor activity
Presenter: Linda Liu, Ph.D., Senior Vice President, Biologics Discovery, Zai Lab
Session Title: Late-Breaking Research: Clinical Research 1
Date/Time: Monday, April 28, 2025, from 2:00 p.m. – 5:00 p.m. CT
Location: McCormick Place Convention Center, Poster Section 53
Poster Board Number: 1
Published Abstract Number: LB204

On April 25, 2025 ALX Oncology Holdings Inc., ("ALX Oncology" or the "Company") (Nasdaq: ALXO), a clinical-stage biotechnology company advancing a pipeline of novel therapies designed to treat cancer and extend patients’ lives, reported encouraging data from an ongoing Phase 1/2 investigator-sponsored trial (IST) of the company’s lead clinical candidate, evorpacept, in combination with standard-of-care rituximab and lenalidomide (R2) in patients with indolent and aggressive relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) (Press release, ALX Oncology, APR 25, 2025, View Source [SID1234652136]). Final results from the Phase 1 portion of the trial will be presented Tuesday, April 29, during a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR) Annual Meeting 2025 in Chicago, Illinois.

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"In patients with indolent B-NHL, increases in certain pro-tumoral macrophages can promote resistance to important frontline standard-of-care treatments, including R2," said Paolo Strati, M.D., the trial’s lead investigator and Associate Professor of Lymphoma-Myeloma at The University of Texas MD Anderson Cancer Center. "Evorpacept is uniquely designed to activate the innate immune system and engage macrophages to enhance the therapeutic benefits of and deepen responses to anti-cancer antibodies such as rituximab. This trial suggests evorpacept has a synergistic effect with R2 that may help improve outcomes and overcome resistance to R2 in this patient population."

The clinical trial conducted by Dr. Strati and colleagues at MD Anderson enrolled a total of 20 patients with indolent (n=18) and aggressive (n=2) R/R B-NHL; all 20 had previously received an anti-CD20 monoclonal antibody (rituximab), 72% had received prior chemoimmunotherapy and 80% had progressed within 24 months from frontline therapy. Patients with indolent NHL had received at least one prior line of systemic therapy. Investigators administered the CD47-blocker evorpacept at two dose levels: 30 mg/kg Q2W (n=3) or 60 mg/kg Q4W (n=17) in combination with standard R2 treatment. The regimen was well- tolerated, and there were no dose-limiting toxicities.

After a median follow-up of 28 months (95% CI, 18-28 months) the two-year progression-free survival (PFS) rate was 69% and two-year overall survival (OS) rate was 84%. Sixteen patients (80%) achieved complete responses and the best overall response rate (ORR) was 90%. As previously reported at the AACR (Free AACR Whitepaper) 2024 Annual Meeting, the CR rate among the 18 patients with iNHL was 83%. This complete response rate achieved by evorpacept + R2 in this trial compares favorably to the 34% historical CR rate for R2 alone. During treatment, a significant increase in T cells and anti-tumoral macrophages was observed.

"The final results from this Phase 1 study reinforce evorpacept’s potential to meaningfully deepen and enhance responses to many of the most important cancer therapies available today, including anti-cancer antibodies such as rituximab, and to thereby help address significant, unmet needs in cancer treatment," said Jason Lettmann, Chief Executive Officer of ALX Oncology. "We look forward to the continued evaluation of evorpacept in patients with previously untreated and high tumor-burden indolent NHL in the Phase 2 portion of this study."

The Phase 2 portion of this IST in patients with previously untreated iNHL is ongoing and has completed enrollment.

Details of the poster to be presented at AACR (Free AACR Whitepaper) 2025 are as follows:

Title: Final results of a phase I trial of evorpacept (ALX148), lenalidomide, and rituximab for patients with B-cell non-Hodgkin lymphoma
Presenter: Paolo Strati, M.D., Associate Professor of Lymphoma-Myeloma, The University of Texas MD Anderson Cancer Center
Session Title: Late-Breaking Research: Clinical Research 3
Date/Time: Tuesday, April 29, 2025, from 2:00 p.m. – 5:00 p.m. CT
Location: McCormick Place Convention Center, Poster Section 53
Poster Board Number: 13
Published Abstract Number: LB369

A copy of the AACR (Free AACR Whitepaper) 2025 IST presentation will be available in the "Publications" section of the ALX Oncology website following the presentation.