On June 2, 2025 Remegen reported that in an oral presentation at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting, Dr. Lin Shen from Beijing Cancer Hospital presented the results of a Phase 2 clinical study conducted in China evaluating the efficacy and safety of disitamab vedotin (DV), developed by Remegen Co., Ltd., and toripalimab (PD-1) combined with CAPOX or trastuzumab as the first-line therapy for HER2-expressing patients with locally advanced or metastatic (la/m) gastric cancer (Press release, RemeGen, JUN 2, 2025, View Source [SID1234653648]). Comparing to the control group who received standard-of-care therapy, the DV combination therapy demonstrated clinically meaningful efficacy improvement, potentially to benefit patients who are non-responders to traditional targeted therapies.

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The data presented are from the Phase 2 part of a randomized, multi-cohort, seamlessly connecting Phase 2/3 study, which enrolled systematic chemotherapy-native patients with different HER2 expression levels. As of April 7, 2025, the results showed:

Among HER2-overexpressing gastric cancer patients, compared to the PD-1-trastuzumab-CAPOX combination therapy, DV and PD-1 + chemotherapy as well as DV and PD-1 + trastuzumab both demonstrated statistically significant efficacy and favorable safety profiles.
Objective response rate (ORR): 66.7% vs 82.4% vs 68.8%;
Median progression-free survival (mPFS): NR vs NR vs 14.1 months, with risk of disease progression decreasing by 54%（HR=0.46）and 41% (HR: 0.59);
12-month PFS rate: 66.3%, 67% and 53.6%；
Common TRAEs of grade 3-5: diarrhea, neutrophil count decreased, platelet count decreased, etc.
In patients with HER2-low-expressing gastric cancer, promising efficacy was observed with DV + PD-1 + CAPOX comparing to PD-1 + CAPOX, with a manageable safety profile.
ORR: 72.0% vs 47.8%;
mPFS: 9.9 vs 7.2 months, with risk of disease progression decreasing by 31% (HR: 0.69);
Common TRAEs of grade 3-5: diarrhea, neutrophil count decreased, platelet count decreased, etc.
Dose optimization conducted in patients with HER2-median/low-expressing gastric cancer. Compared to PD-1 + CAPOX, DV at 2.5 mg/kg or 2.0 mg/kg combined with PD-1 + reduced-dose CAPOX showed significant efficacy, and better safety over the full-dose chemotherapy.
ORR: 71.4% vs 66.7% vs 56.3%;
6-month PFS rate: 71.4%，72.7% and 53.3%.
Globally, this is the first study to explore the triple combination therapy of "HER2 ADC + PD-1 + targeted medication" as first-line treatment of patients with la/m gastric cancer, pioneering a new mode of synergistic therapy. The multi-cohort design of this study provides precision treatment regimen for gastric cancer patients with different level of HER2 expression. For the HER2-overexpressing gastric cancer patients, DV + PD-1 + trastuzumab has the potential to become the new standard first-line treatment; for the HER2-low-expressing gastric cancer patients, DV + PD-1 + chemotherapy has the potential to fill the treatment gap of these patients. Based on the data obtained from the phase 2 study, the phase 3 clinical study of the triple combination therapy in patients with HER2-median/low-expressing gastric cancer has been initiated in April, 2025, in which 616 participants were planned to be enrolled, to further validate the efficacy of the DV combination therapy.

Gastric cancer is the fifth most common malignant tumor in the world, and China accounts for about 42.6% of new cases and 45.0% of deaths worldwide. HER2 is an important target in the treatment of gastric cancer, while the traditional targeted drug trastuzumab is only effective in the population with high expression (IHC 3+ or IHC 2+/FISH+), and can easily become resistant. There is a lack of effective targeted therapy options for patients with low/median HER2 expression (IHC 1+ or IHC 2+/FISH-), and the efficacy of chemotherapy combined with immunotherapy is not satisfactory.

As the first domestic HER2-targeted ADC drug in China, DV not only precisely kills tumor cells with HER2 over expression but also attacks adjacent cells with HER2 low expression through the bystander effect. Preclinical studies have also shown that the combination of DV with PD-1 inhibitor and trastuzumab can enhance anti-tumor activity.

On June 2, 2025 KAHR, a clinical-stage biotech company developing DSP107, a first-in-class bi-specific 4-1BB T-cell engager that activates innate and adaptive immunity to treat solid tumors, reported positive results from the Phase 2 dose expansion cohort of DSP107 in combination with atezolizumab (Tecentriq), an anti-PD-L1 cancer immunotherapy, in patients with 3rd line microsatellite stable metastatic colorectal cancer (MSS-CRC) (Press release, KAHR Medical, JUN 2, 2025, View Source [SID1234653647]). In addition to its favorable safety profile, the combination has shown anti-tumor activity and extended survival including in patients with liver metastases. The results were presented in an oral presentation by Anwaar Saeed, MD, Associate Professor of Medicine, University of Pittsburgh Medical Center and Director, Gastrointestinal Disease Center, UPMC Hillman Cancer Center at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2025 Annual Meeting, May 30 – June 3, 2025, in Chicago, IL.

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"Colorectal cancer, the second largest cause of cancer deaths worldwide, is considered a ‘cold’ tumor that usually does not elicit an efficient immune response," said Dr. Saeed. "This immunotherapy combination showed durable results in MSS-CRC patients. Not only is the median survival of DSP107 with atezolizumab longer than current standard treatments, it is also very well tolerated by patients, without the severe, sometimes life-threatening side effects of chemotherapy in such advanced lines of treatment. Importantly, the majority of patients in the combination cohort had active liver metastases and the activity and survival benefit were also seen in these patients, who are very difficult to treat, suggesting that DSP107 in combination with a PD1/PD-L1 checkpoint inhibitor may become an effective immunotherapy treatment option for this patient population."

Yaron Pereg, Ph.D., Chief Executive Officer of KAHR, said, "We are extremely encouraged by the dose expansion data, showing objective responses and extended survival in response to DSP107 in combination with atezolizumab in patients with 3rd line MSS-CRC. We look forward to initiating a Phase 2b, randomized, controlled study to confirm these promising efficacy signals. In addition, we expect data in 2026 from a Phase 2 dose expansion cohort in Non-small Cell Lung Cancer (NSCLC), the leading cause of cancer deaths worldwide."

Results from the completed dose expansion cohort show that DSP107 monotherapy and combination treatment with atezolizumab were well tolerated with no dose limiting toxicities. The median OS from the efficacy-evaluable patients who received DSP107 monotherapy (n=19) and combination therapy with atezolizumab (n=21) has not been reached, but currently (May 2025 cutoff) stands at 8.1 and 17 months, respectively. Disease control was demonstrated in 21% (monotherapy) and 62% (combination) of evaluable patients including a patient who achieved a complete response (> 2.5 years) and a patient with a deep (86% target lesion reduction) and durable (> 16 months) confirmed partial response and disappearance of pulmonary and hepatic metastases. Immunofluorescence analysis of baseline tumor biopsies demonstrated very high levels of CD47 expression, the DSP107 target, in all samples collected from liver metastases.

The MSS-CRC dose expansion phase of the study was an open label, multi-center trial (NCT04440735) that enrolled patients with 3rd line MSS colorectal cancer patients, treated weekly with 10 mg/kg DSP107 infusions and atezolizumab (1200 mg) every three weeks, until disease progression. The primary objective was to determine the safety and tolerability of DSP107 in combination with atezolizumab. The secondary objective was to assess the preliminary efficacy of DSP107 in combination with atezolizumab.

Presentation information:

Abstract Title: Phase 2 dose expansion study of DSP107, a first-in-class bi-specific 4-1BB T-cell engager, with and without atezolizumab in metastatic MSS colorectal cancer patients.

Abstract Number for Publication: 3517

About DSP107

KAHR’s lead drug candidate, DSP107, is a first-in-class bi-specific 4-1BB T-cell engager utilizing CD47 overexpression as a tumor anchor. DSP107 binds to CD47 that cancer cells express on their cell surface. Once bound, DSP107 converts the CD47 signal, which cancer uses to camouflage itself from the innate immune system, into a 4-1BB signal, which attracts and activates adaptive immune cells, primarily cancer cytotoxic CD8 T-cells. In this way, DSP107 engages both parts of the immune system in a wholistic anti-cancer response. This is particularly relevant in colorectal cancer, where 70%+ of the metastatic patients have metastases in the liver, and where liver metastases highly express CD47 in response to first- and second-line chemotherapy treatments. Previous attempts to treat colorectal cancer with immunotherapy have failed as there is a lack of immune cells in the tumor. DSP107 is unique in that it takes advantage of CD47 expression to drive immune cells into the tumor. DSP107 is also being tested in Phase 2 expansion cohort in 2L/3L PD1-experienced NSCLC.

About microsatellite stable metastatic colorectal cancer (MSS-CRC)

Microsatellite stable metastatic colorectal cancer (MSS-CRC) is a subtype of colorectal cancer that lacks deficiencies in the DNA mismatch repair system, resulting in stable microsatellite regions within the genome. Unlike microsatellite instability-high (MSI-H) tumors, MSS-CRC exhibits lower tumor mutational burden and is less responsive to immunotherapy. MSS tumors represent the majority of colorectal cancer cases and are typically more challenging to treat. Standard treatment for metastatic MSS-CRC often involves a combination of chemotherapy, targeted therapy, and in select cases, surgical intervention.

On June 2, 2025 OnCusp Therapeutics, Inc., a clinical-stage biopharmaceutical company dedicated to transforming cutting-edge preclinical innovation into clinically validated treatments for cancer patients, reported initial Ph1a data from its ongoing Phase 1 open-label, multicenter dose escalation and expansion study evaluating CUSP06, a CDH6-directed antibody-drug conjugate (ADC) with a differentiated profile, in patients with platinum-refractory/resistant ovarian cancer and other advanced solid tumors (Press release, OnCusp Therapeutics, JUN 2, 2025, View Source;302470621.html [SID1234653646]). The data are being presented today at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago, Illinois.

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"We are excited by the early results, especially in platinum-resistant HGSOC, which demonstrated promising activity in a heavily pretreated population without requiring CDH6 biomarker selection," said Dr. Bing Yuan, Co-Founder and CEO of OnCusp Therapeutics. "These data, together with previously presented preclinical findings, underscore the best-in-class potential of CUSP06. We look forward to observing promising data in the Phase 1b study and to bringing this therapy to patients with ovarian cancer and other CDH6-expressing solid tumors."

The Phase 1 trial is an open-label, multicenter, first-in-human study of CUSP06. The primary objective of the study is to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of CUSP06 in patients with platinum-refractory/resistant ovarian cancer and other advanced solid tumors. The Phase 1a portion will determine the recommended doses for expansion and the Phase 1b portion will focus on further characterizing safety and efficacy in select tumor types.

As of May 13, 2025, data are available for 37 patients who have received CUSP06 once every three weeks (Q3W) at doses ranging from 1.6 to 5.6 mg/kg. These patients were heavily pretreated, with a median of 4 prior lines of therapy. Promising efficacy was observed in patients with heavily pretreated platinum-resistant HGSOC without CDH6 pre-selection. The overall response rate (ORR) was 36% in HGSOC (9/25; 5 confirmed (including 2 responders who had previously received mirvetuximab treatment) and 4 unconfirmed partial responses (PRs)). All patients with unconfirmed PRs remain on treatment. The ORR reached 50% at both 4.0 mg/kg + prophylactic granulocyte colony-stimulating factor (G-CSF) and 4.4 mg/kg + G-CSF cohorts (3/6 and 1/2 patients, respectively); all responders remain on treatment. The clinical benefit rate (CBR) was 92% (23/25). CA-125 responses occurred in 45% of Gynecologic Cancer InterGroup (GCIG)-evaluable HGSOC patients, further supporting clinical activity. Responses were seen in low and high-CDH6-expressing tumors. CUSP06 has been well tolerated, with manageable hematologic toxicities as the most common treatment-related adverse events. These Phase 1a safety and efficacy results support continued evaluation of CUSP06 in platinum-resistant HGSOC and other CDH6-positive tumors in Phase 1b expansion cohorts.

CUSP06 was recently granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of patients with platinum-resistant ovarian cancer.

Poster Presentation Details:

Title: First-in-human (FIH) Phase 1 study of CUSP06, a cadherin-6 (CDH6)-directed antibody-drug conjugate (ADC), in patients with platinum-refractory/resistant ovarian cancer and other advanced solid tumors.
Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Date and Time: June 2 – 1:30 PM CDT
Abstract Number: 3042
Poster Number: 357
Location: Hall A

About CUSP06

CUSP06, a CDH6 ADC, is composed of a proprietary antibody with high CDH6 binding affinity, a protease-cleavable linker, and an exatecan payload (a potent and clinically validated topoisomerase-1 inhibitor). The linker is designed to complement the exatecan payload, enabling a stable and homogeneous ADC. The payload is a weak substrate for BCRP/P-gp, which are drug efflux pumps that drive chemoresistance to many therapies. In preclinical data, this linker-payload has been shown to have an increased "bystander effect" compared with competitor ADCs. CUSP06 has a drug-to-antibody ratio of eight. OnCusp obtained the exclusive global rights (outside of China) to lead the development and commercialization of CUSP06 from Multitude Therapeutics in 2022. CUSP06 is being evaluated in a Phase 1 study in patients with platinum refractory/resistant ovarian cancer and other advanced solid tumors. Additional information on the CUSP06-1001 (NCT06234423) trial can be found at ClinicalTrials.gov.

On June 2, 2025 SkylineDx, an innovative diagnostics company specializing in the research and development of molecular diagnostics for oncology, inflammatory and infectious diseases, reported a new independent study at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting demonstrating that its Merlin Assay (CP-GEP), a genomic test to guide treatment decisions in early-stage melanoma, can reliably identify patients with head and neck (H&N) melanoma at high risk for recurrence—even in the absence of sentinel lymph node biopsy (SLNB) (Press release, SkylineDx, JUN 2, 2025, View Source [SID1234653645]).

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SLNB may be challenging in patients with H&N melanoma due to the regional course of cranial nerves and lymphatic drainage, so the aim of the study was to validate CP-GEP’s ability to stratify these patients for their risk of recurrence. The study analyzed a subgroup of 206 patients with H&N melanoma, including a large proportion with lentigo maligna, a subtype common in older adults, from a previously published cohort of 930 stage I/II melanoma patients who did not undergo SLNB [2]. Using CP-GEP, researchers stratified patients into low- and high-risk categories based on tumor biology. Results showed a dramatic difference in outcomes:

10-year relapse-free survival (RFS) was 87.9% in CP-GEP Low-Risk patients compared to 45.8% in the High-Risk group (Hazard Ratio (HR) 7.35; p<0.001).
10-year distant metastasis-free survival (DMFS) was 94.7% for CP-GEP Low-Risk and 75.8% for High-Risk patients (HR 6.28; p<0.001).
10-year melanoma-specific survival (MSS) was 96.4% for Low-Risk vs. 74.0% for High-Risk (HR 10.22; p<0.01).
"The Merlin Assay is a major advancement in personalized care for patients with head and neck melanoma," said Principal Investigator, Teresa Amaral MD, PhD "SLNB can be technically challenging in the head and neck region. Merlin offers a powerful alternative for clinicians to make informed decisions without subjecting patients to unnecessary and potentially complicated surgical procedures."

"The findings build on prior data and highlight Merlin’s growing clinical utility in a region of the body where lymphatic mapping is less reliable and patient frailty often limits invasive procedures", said Chief Scientific Officer at SkylineDx, Dr. Jvalini Dwarkasing. "For the more than 20% of early-stage melanoma cases in the head and neck area, these results support that Merlin helps fill a critical gap in risk stratification and care planning."

About the Merlin Assay (CP-GEP)

CP-GEP is a non-invasive prediction model for cutaneous melanoma patients and is the only commercially available GEP test that combines clinicopathologic (CP) variables with gene expression profiling (GEP) into a single integrated algorithm. This CP-GEP model is also the only GEP test that provides a binary stratification of all patients based on being High or Low Risk for metastasis and thereby assign them to the appropriate surgical action categories as listed in evidence-based cancer treatment, prevention and screening guidelines. The advanced CP-GEP model was developed by Mayo Clinic and SkylineDx and is the latest commercially launched GEP test, which has been clinically validated in multiple studies on a global basis. The test has been launched in the United States and Europe as Merlin. SkylineDx collaborates with diagnostic service providers globally to bring this test to market and increase patient access. More information (including references) may be obtained at www.falconprogram.com and www.merlinmelanomatest.com.

On June 2, 2025 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, reported updated positive clinical and biomarker data from its Phase 2 clinical trial of lucicebtide (formerly known as ST101), a first-in-class antagonist of C/EBPβ, in patients with glioblastoma (GBM) (Press release, Sapience Therapeutics, JUN 2, 2025, View Source [SID1234653644]). The data were featured during an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place May 30-June 3, 2025, in Chicago and online.

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"GBM represents a devastating disease carrying a poor prognosis and high mortality rate, and there is a significant need for new, efficacious treatment options," said Fabio Iwamoto, MD, Division of Neuro-Oncology, New York-Presbyterian/Columbia University Irving Medical Center. "The growing body of data from this Phase 2 study, which demonstrate a marked progression free and overall survival benefit, continue to support that lucicebtide could serve as a well-tolerated, meaningful addition to the GBM treatment paradigm. I look forward to deepening our understanding of the potential for lucicebtide to improve outcomes and offer hope to patients for whom limited alternatives exist."

Sapience Chief Medical Officer, Dr. Abi Vainstein-Haras, added, "These updated results reinforce lucicebtide’s compelling clinical and safety profile, and support its potential to serve as a standalone therapy or in combination with existing treatments. The opportunity to collect biopsies in this patient population gave us a unique opportunity for biomarker analysis to demonstrate the meaningful effects of lucicebtide."

Oral Presentation Highlights Include:

Lucicebtide was well-tolerated as a monotherapy and in combination with standard-of-care (SOC) agents.
Lucicebtide combination with SOC Window-of-Opportunity study in newly diagnosed GBM cohort (n=9), data cut May 6, 2025:
5/9 patients yet to experience disease progression (10-24+ months)
6/9 patients are alive as of the data cutoff date (10-26+ months)
Lucicebtide Window-of-Opportunity study in recurrent GBM cohort (n=9), data cut May 6, 2025:
4/9 patients had disease control, with two partial responses
3/9 patients remain alive as of data cutoff
Window-of-Opportunity biomarker results demonstrate:
Lucicebtide crossed the blood-brain barrier, demonstrated uptake into the tumor and target engagement
Immune activation in the tumor microenvironment (TME) evidenced by increased macrophage M1/M2 ratio and CD8 T cell infiltration
Meaningful reductions in mesenchymal gene signature in tumor cells as shown by spacial transcriptomics analysis
Data support lucicebtide and C/EBPβ antagonism as a differentiated and promising therapeutic approach for patients with GBM.
A copy of the presentation is available under the Presentations section of the Sapience Therapeutics website.

About Lucicebtide (formerly known as ST101)

Lucicebtide, a first-in-class antagonist of C/EBPβ, has completed the main portion of a Phase 2 dose expansion study in recurrent glioblastoma (rGBM) (NCT04478279). An ongoing Window-of-Opportunity sub-study is evaluating lucicebtide in combination with radiation and temozolomide in patients with newly diagnosed GBM (ndGBM) and as a monotherapy in patients with rGBM, with patients receiving lucicebtide before and after surgical resection in both cohorts. Lucicebtide has been granted Fast Track designation for rGBM from the U.S. Food and Drug Administration (U.S. FDA) and orphan designations for glioma from the U.S. FDA and the European Commission.