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.

On June 2, 2025 Eli Lilly and Company (NYSE: LLY) reported new Phase 1 data showing that its folate receptor alpha (FRα) antibody-drug conjugate (ADC) (LY4170156) demonstrated an encouraging safety profile and anti-tumor activity across dose and FRα expression levels in women with heavily pre-treated platinum-resistant ovarian cancer, including patients previously treated with mirvetuximab soravtansine (Press release, Eli Lilly, JUN 2, 2025, View Source [SID1234653643]). A preliminary overall objective response rate (ORR) of 55% was observed at the potential recommended Phase 2 dose of 4 mg/kg. Lilly’s FRα targeting ADC is composed of an Fc-silent, FRα specific humanized monoclonal antibody linked to exatecan, a topoisomerase I inhibitor, via a proprietary cleavable polysarcosine linker. These data will be presented today in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"ADCs have begun to change the treatment paradigm for some women with ovarian cancer, but a large proportion of patients still have a significant need for new therapies that improve outcomes regardless of FRα expression level," said Isabelle Ray-Coquard, M.D., Ph.D., president of the ENGOT (European Network of Gynecological Oncology Trial) group, medical oncologist at the Centre Léon Bérard Lyon France and principal investigator for the trial. "These initial data show activity across all doses and levels of FRα expression, including in patients previously treated with a FRα targeting treatment. Taken together with the emerging safety and tolerability profile, these data demonstrate early potential to meaningfully improve outcomes for women living with advanced ovarian cancer."

As of the March 9, 2025 data cutoff, the study enrolled 95 participants with high-grade serous ovarian cancer across four dose levels (2 – 6 mg/kg). Patients received a median of five prior systemic regimens (range 1-10), and 15% were previously treated with mirvetuximab soravtansine. Among the 95 patients, 51% had tumors with FRα expression less than 75%, 34% had FRα expression of 75% or higher, and 16% had expression results pending. Key endpoints were safety, pharmacokinetics, and anti-tumor activity per RECIST v1.1.

Efficacy results demonstrate responses at all dose levels, across all FRα expression levels, including in patients who progressed on prior mirvetuximab soravtansine. In the 58 efficacy-evaluable patients (37 patients remain ongoing prior to first response assessment and were therefore not yet efficacy-evaluable at the time of the data cutoff), the ORR was 45% (26/58 patients), and the disease control rate was 74% (43/58). At the potential recommended Phase 2 dose of 4 mg/kg, the ORR was 55% (11/20 patients). The most common treatment-emergent adverse events across all dose levels included nausea (64%), anemia (40%), fatigue (32%), vomiting (32%), diarrhea (28%), and neutropenia (27%). Treatment-emergent neuropathy and ocular toxicity has not been observed to date. No maximum tolerated dose has been established.

"We are excited to share these first clinical data for our FRα targeting ADC, demonstrating a promising tolerability and efficacy profile across all FRα expression levels," said David Hyman, M.D., Chief Medical Officer, Lilly. "Based on these results, we believe there is the potential to significantly expand the number of ovarian cancer patients who could benefit from a FRα ADC. We are now focused on rapidly advancing this potential new medicine into registrational Phase 3 clinical trials."

For more information on Lilly’s oncology pipeline click here.

About LY4170156
LY4170156 is an investigational, next-generation antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα). FRα is a cell-surface glycoprotein encoded by the gene FOLR1 that binds to the essential nutrients folic acid and reduced folates, bringing them into cells to facilitate cell division and growth.1,2 FRα is overexpressed in many solid tumors such as ovarian, non-small cell lung, and colorectal cancers.1,3,4

LY4170156 was designed to target FRα across expression levels with an improved therapeutic index. LY4170156 is composed of an Fc-silent, FRα specific humanized monoclonal antibody linked to exatecan, a topoisomerase I inhibitor, via a proprietary cleavable polysarcosine linker (PSARlink). PSARlink’s unique structure "masks" the cytotoxic molecules enabling them to stay in the body longer, providing the potential to broaden the therapeutic index of ADCs. LY4170156 is currently being studied in patients with ovarian cancer as well as other FRα-expressing solid tumors, NCT06400472.