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Johns Hopkins Medicine Initiates Patient Enrollment for RenovoRx’s Ongoing Phase III TIGeR-PaC Clinical Trial

On April 29, 2025 RenovoRx, Inc. ("RenovoRx" or the "Company") (Nasdaq: RNXT), a life sciences company developing innovative targeted oncology therapies and commercializing RenovoCath, a novel, FDA-cleared drug-delivery device, reported that Johns Hopkins Medicine is now initiated to enroll patients with locally advanced pancreatic cancer (LAPC) in RenovoRx’s ongoing Phase III TIGeR-PaC clinical trial (Press release, Renovorx, APR 29, 2025, View Source [SID1234652338]). Johns Hopkins Medicine becomes the newest addition to a distinguished network of clinical cancer sites across the United States participating in this important trial.

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The initiation of patient enrollment at Johns Hopkins Medicine will be at their Sibley Memorial Hospital campus and marks the most recent site to support RenovoRx’s path to completing patient enrollment for the trial. RenovoRx is expecting to achieve full enrollment in the TIGeR-PaC trial during 2025.

In addition, RenovoRx announced that John Hopkins Medicine’s Valerie Lee, MD, Medical Oncologist, has been appointed as TIGeR-PaC Principal Investigator (PI) at Johns Hopkins Medicine. Michael J. Pishvaian, MD, PhD, Director of Gastrointestinal, Developmental Therapeutics and Clinical Research Programs at John Hopkins Medicine, currently serves as Trial Chairman for the entire TIGeR-PaC trial.

The TIGeR-PaC trial is evaluating RenovoRx’s lead drug-device combination product candidate, intra-arterial delivery of gemcitabine (IAG) via the FDA-cleared RenovoCath device, which uses RenovoRx’s proprietary Trans-Arterial Micro-Perfusion (TAMP) therapy platform for the treatment of LAPC. This drug-device combination product candidate is currently under FDA investigation and has not been approved for commercial sale. The trial is comparing treatment with IAG in LAPC to the current standard-of-care (systemic intravenous chemotherapy).

"We are pleased that Johns Hopkins Medicine has been initiated to begin enrollment in our ongoing Phase III TIGeR-PaC clinical trial," said Leesa Gentry, Chief Clinical Officer of RenovoRx. "The addition of this prestigious cancer center further strengthens our trial. The philosophy of Johns Hopkins Medicine’s leading researchers and clinicians aligns strongly with our vision of providing specialized medicine that translates into personalized care for improved patient outcomes. Dr. Michael Pishvaian, who has served as our TIGeR-PaC Trial Chair since the trial’s inception, will continue to provide deep understanding of the pancreatic cancer landscape. With the addition of Johns Hopkins Medicine as a clinical trial site, Dr. Valerie Lee will join the trial serving as Principal Investigator. This new clinical site will help drive enrollment of the TIGeR-PaC trial to completion as they treat a large number of patients diagnosed with pancreatic cancer. We are proud to partner with Johns Hopkins Medicine as well as our other TIGeR-PaC clinical sites as they strive to provide the best in care for patients diagnosed with difficult-to-treat tumors like pancreatic cancer."

At Johns Hopkins Medicine, Dr. Lee’s expertise includes management of gastrointestinal malignancies, including gastric, colon, and pancreatobiliary cancers. She also oversees multiple early-phase clinical trials, with her research being published in numerous peer-reviewed journals.

Johns Hopkins Medicine’s Sibley Memorial Hospital campus ranks among the top hospitals in the Washington, D.C., metropolitan area, delivering comprehensive healthcare services to local communities. The hospital provides an extensive array of care, including medical, surgical, intensive care, obstetric, oncology, and orthopedic services, alongside numerous inpatient and outpatient offerings.

The current protocol and statistical analysis plan for the TIGeR-PaC trial requires 114 randomized patients, with 86 events (i.e., patient deaths) necessary to complete the final analysis. As of March 28, 2025, 90 patients have been randomized with 50 events having occurred. A second interim analysis will be triggered by the 52nd event. The timing required to analyze the data after the 52nd event is expected to take several months and includes a full review with recommendations by the TIGeR-PaC Data Monitoring Committee. RenovoRx currently anticipates the 52nd event to occur during the second quarter of 2025. The key recommendation from the Data Monitoring Committee on whether or not to continue the study based on the data reviewed is expected to be announced in the second half of 2025.

Innate Pharma Highlights Preclinical Anti-Tumor Efficacy Data of Its Antibody Drug Conjugate IPH4502 at the AACR 2025 Annual Meeting

On April 29, 2025 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported new preclinical data for IPH4502, its novel and differentiated topoisomerase I inhibitor Antibody Drug Conjugate (ADC) targeting Nectin-4 (Press release, Innate Pharma, APR 29, 2025, View Source [SID1234652337]). The data were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025.

Nectin-4 targeting is validated by enfortumab vedotin (EV), an ADC with a monomethyl auristatin E (MMAE) payload, approved for urothelial carcinoma (UC), an indication with high Nectin-4 expression. However, EV discontinuation due to toxicity, disease relapse, or treatment ineligibility, along with its limited efficacy in tumors with lower Nectin-4 expression, underscores the need for a differentiated Nectin-4 ADC with improved therapeutic window and improved mechanisms of action.

IPH4502 demonstrated anti-tumor activity in EV-resistant patient-derived xenograft (PDX) model with upregulation of multi-drug resistance protein 1 (MDR1), supporting its potential to overcome resistance mechanisms in EV-refractory disease.

Beyond UC, IPH4502 also exhibited anti-tumor activity in preclinical models of triple-negative breast cancer, head and neck squamous cell carcinoma, and esophageal cancer, suggesting broader potential clinical applicability.

In addition, in preclinical tumor models with low Nectin-4 expression, IPH4502 showed superior anti-tumor activity compared to a clinical-stage Nectin-4-exatecan ADC supported by higher internalization, cytotoxicity, and bystander killing effect.

"We are highly encouraged by these preclinical data, which suggest that IPH4502 has the potential to translate into improved clinical benefit in indications with unmet medical need. These findings also reinforce the rationale for our ongoing Phase 1 trial. We look forward to sharing initial clinical data in 2026 as the program advances," said Sonia Quaratino, Chief Medical Officer of Innate Pharma.

IPH4502 is currently investigated in a Phase 1 trial in advanced solid tumors known to express Nectin-4 (NCT06781983).

The poster is available on Innate Pharma’s website.

About IPH4502

IPH4502 is a differentiated topoisomerase I inhibitor Antibody Drug Conjugate (ADC) conjugated to exatecan targeting Nectin-4, a cell adhesion molecule that is overexpressed in several types of solid tumors, such as urothelial carcinoma, breast cancer, non-small cell lung cancer or gastro-intestinal tract cancer.

IPH4502 is currently investigated in a Phase 1 trial in advanced solid tumors. The Phase 1 trial will assess the safety, tolerability, and preliminary efficacy of IPH4502 in different solid tumors known to express Nectin-4, including but not limited to urothelial carcinoma, non-small cell lung, breast, ovarian, gastric, esophageal, and colorectal cancers. The study plans to enroll approximately 105 patients.

In preclinical models, IPH4502 demonstrates strong bystander killing effect, and efficient internalization, enabling a potent anti-tumor activity in models with various Nectin-4 expression levels. Additionally, IPH4502 shows efficacy in models resistant to MMAE-ADC. These results support its potential for development beyond UC and in cancer patients treated with MMAE-based ADCs.

SOTIO Reports Promising Preclinical Data on Antibody-Drug Conjugates SOT109 and SOT106, Underscoring Best-in-Class Potential for Solid Tumor Treatments

On April 29, 2025 SOTIO Biotech, a clinical-stage biopharmaceutical company owned by PPF Group, this week reported preclinical data on two of its leading antibody-drug conjugate (ADC) candidates, SOT109 and SOT106, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL (Press release, SOTIO, APR 29, 2025, View Source [SID1234652336]).

Preclinical data on SOT109 (anti-CDH17 ADC) and SOT106 (anti-LRRC15 ADC) demonstrate strong anti-tumor activity and favorable tolerability profiles across multiple tumor models, supporting their potential as groundbreaking ADC therapies for various solid tumor types.

SOT109 is tailored to be a best-in-class ADC exploiting the highly promising target of CDH17 for treatment of gastrointestinal cancers including colorectal cancer (CRC), where unmet need remains very high. ADCs have shown limited clinical success in CRC to date largely due to a lack of ideal target antigens. CDH17 is a highly promising target antigen homogenously overexpressed in more than 90% of CRC and abundantly expressed in other GI cancers. Its expression in normal adult tissues is largely restricted to the GI tract, reducing the risk of off-target toxicity. SOT109 utilizes a proprietary, highly internalizing and fully human antibody combined with Synaffix B.V.’s leading ADC technology platform. Both the antibody and the epitope it is targeting, as well as the linker/payload design, have been selected to maximize its efficacy and safety.

SOTIO’s poster presentation on SOT109 showed the following:

SOT109 exhibited potent efficacy, producing significant and sustained tumor regressions in several in vivo colorectal tumor models, including cell-derived and patient-derived xenografts.
The doses tested in these studies were well tolerated in mice, with no dose-limiting toxicities observed. Subsequent studies in non-human primates confirmed a favorable pharmacokinetic and safety profile.
SOT106, leveraging LigaChem Biosciences’ clinically validated ConjuAll ADC platform for tumor-specific MMAE release, is a potentially best-in-class ADC for the clinically-validated target LRRC15. SOTIO’s oral presentation on SOT106 showed the following:

SOT106 demonstrated exceptional efficacy in an LRRC15 low-expressing patient-derived xenograft model of pediatric osteosarcoma, achieving significant tumor regression where a first-generation LRRC15-targeting ADC benchmark therapy was ineffective. This further supports its therapeutic potential across a broad range of target expression levels.
Complete responses and potent antitumor efficacy were also observed across a range of other models where LRRC15 is expressed directly on tumor cells, including multiple subtypes of soft tissue sarcoma, a therapy-resistant non-small-cell lung cancer model, and head and neck squamous cell carcinoma.
SOT106 displays a favorable pharmacokinetic and safety profile, good stability in vivo, and a high therapeutic index.
"The data we presented at AACR (Free AACR Whitepaper) this week highlights the strength of our next-generation ADCs by addressing areas of high unmet need in oncology," said Martin Steegmaier, Ph.D., chief scientific officer at SOTIO. "SOT109 continues to show excellent tolerability and strong anti-tumor activity across multiple preclinical models of colorectal cancer, while SOT106 offers a novel precision approach with broad applicability in LRRC15+ sarcomas and other solid tumors. These findings mark important progress in our pipeline and reinforce our commitment to developing highly differentiated ADCs for difficult to treat solid tumors."

Presentation materials will be available here after the presentation concludes.

Guardant Health Presents Data Demonstrating Strong Performance of Shield Multi-Cancer Detection Test Across 10 Tumor Types

On April 29, 2025 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported data today from a study showing that its methylation-based Shield multi-cancer detection (MCD) test demonstrated high specificity and clinically meaningful sensitivity across ten tumor types,* while also providing information to guide clinical diagnostic evaluation (Press release, Guardant Health, APR 29, 2025, View Source [SID1234652335]). The study was presented at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting. Results of the study served as the basis for the selection of the blood-based Shield MCD test by the National Cancer Institute (NCI) for inclusion in its upcoming Vanguard Study evaluating emerging MCD technology.

Data presented in the oral session titled "Evaluation of a plasma cell-free DNA methylation-based multi-cancer detection test" showed that the Shield MCD test demonstrated 98.5% specificity and 60% overall sensitivity, with 74% sensitivity across the six most aggressive cancers (defined as those with the shortest survival rates), including esophageal-gastric, hepatocellular, lung, ovarian and pancreas. The test also demonstrated 89% accuracy for primary or secondary cancer signal of origin (CSO) prediction.

"There are still many types of cancer that are difficult to detect with existing technologies until the late stages. This strong data reinforces the potential of the Shield test to detect multiple cancers earlier through a simple blood draw," said AmirAli Talasaz, Guardant Health co-founder and co-CEO. "This study was a critical step in evaluating this innovative technology as a new screening option we can bring to patients to help reduce cancer deaths."

The blinded case-control study evaluated samples from 778 individuals with either a known diagnosis of cancer or who were cancer free (by self-report). Age range of participants was 40-78 years (median age 62); 55% were female and 79% were white. Across the ten cancer types, overall sensitivity per type ranged from 96% (esophageal-gastric (stomach)) to 21% (prostate) at 98.5% specificity (Table 1).

Table 1: Overall and per cancer Sensitivity and CSO Accuracy Results at 98.5% Specificity (n=403)

Sensitivity, %

Primary or Secondary CSO
Accuracy, %

Overall, 375

60%

89%

Bladder, 13

62%

75%

Breast, 86

45%

92%

Colorectal, 41

83%

94%

Esophageal-Gastric (Stomach) 25

96%

92%

Hepatocellular, 16

94%

73%

Lung, 57

67%

97%

Ovarian, 20

70%

93%

Pancreas, 59

68%

80%

Prostate, 59

21%

83%

"Impressively, this initial cohort analysis of the Shield MCD test met overall performance expectations, with particularly strong sensitivity in the six most aggressive cancers for which early detection is key," said William Greenleaf, Ph.D., study co-author, consultant for Guardant Health and professor of genetics at Stanford University School of Medicine. "These results show this blood-based MCD test holds promise for detection of multiple cancer types, and thus for detection in asymptomatic adults when treatment is more effective."

The full data abstract and a list of all abstracts being presented at the meeting can be found on the AACR (Free AACR Whitepaper) website. For more information on the NCI Vanguard Study, please visit the study website.

D3 Bio Announces Nature Medicine Publication and AACR 2025 Presentation Highlighting D3S-001 as a Next-Generation KRAS G12C Inhibitor with Best-in-Class Potential

On April 29, 2025 D3 Bio, a clinical-stage biotechnology company pioneering precision oncology therapies, reported the simultaneous publication of landmark clinical data on its lead investigational drug D3S-001 in Nature Medicine and oral presentation of updated results at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, D3 Bio, APR 29, 2025, View Source [SID1234652334]). These data affirm D3S-001’s differentiated mechanism of action, favorable safety profile and compelling efficacy in patients with KRAS G12C mutation–addicted cancers, including patients previously treated with first-generation KRAS G12C inhibitors.

Promising Efficacy in G12Ci-Naïve and Resistant Patients

In a Phase 1a/1b clinical study (NCT05410145), D3S-001 demonstrated an overall objective response rate (ORR) of 73.5% in KRAS G12C inhibitor-naïve patients across multiple tumor types, including:

66.7% in non–small cell lung cancer (NSCLC)
88.9% in colorectal cancer (CRC)
75.0% in pancreatic ductal adenocarcinoma (PDAC)
Additionally, in 20 patients with NSCLC who had previously been treated with and progressed on first-generation G12C inhibitors, including sotorasib and adagrasib, D3S-001 achieved a 30.0% overall response rate (ORR) and 80.0% disease control rate (DCR), providing direct clinical evidence of its ability to overcome acquired resistance to first-generation G12Ci therapies.

"These findings demonstrate that D3S-001 fulfills the defining qualities of a next-generation KRAS G12C inhibitor: fast and complete target engagement, favorable safety, consistent and promising efficacy across all tumor types, brain penetration, and ability to overcome first-generation resistance," said Byoung Chul Cho, MD, PhD, lead and co-supervisory author and Professor and Head of Yonsei Cancer Center, Yonsei University College of Medicine. "We believe it is a truly new-generation KRAS G12C inhibitor with the potential to overcome the limitations of the first-generation inhibitors and become a cornerstone therapy for KRAS G12C-driven cancers."

AACR 2025 Data Highlights the Activity of D3S-001 in Overcoming Resistance in Patients with NSCLC Who Have Progressed on First-Generation G12C Inhibitors

At AACR (Free AACR Whitepaper) 2025, D3 Bio shared updated results from a Phase 2 expansion cohort of NSCLC patients who had previously been treated with FDA-approved or other experimental G12C inhibitors. The compound demonstrates encouraging clinical benefits in this patient population. The data include:

60% of patients experienced tumor shrinkage
30% achieved partial responses
80% disease control rate
11 of 14 ctDNA-positive patients achieved >90% G12C MAF reduction, with 6 achieving partial response (a 43% response rate in the ctDNA-positive population)
Responses were observed in patients with KRAS G12C amplification, a known resistance mechanism to first-generation inhibitors, consistent with previous preclinical observations
The results support D3S-001’s unique ability to overcome molecular resistance in a population with urgent unmet medical needs.

"The clinical data, published at Nature Medicine and presented at AACR (Free AACR Whitepaper), validates D3S-001 as a promising treatment for patients with KRAS G12C–driven tumors, both naïve and refractory, to first-generation inhibitors," said Tony Mok, MD, co-supervisory author of the Nature Medicine paper, Professor of Clinical Oncology at the Chinese University of Hong Kong, and a global thought leader in targeted therapy for lung cancer. "Its potential to induce compelling responses in these challenging cases offers hope for a patient population with limited treatment options."

"At D3 Bio, we believe that solid science, combined with strong collaboration with global thought leaders, is the foundation for driving the field forward," said George Chen, MD, Founder, Chairman, and CEO of D3 Bio. "Our Cancer Discovery paper reported the new mechanism and properties of D3S-001 in preclinical settings, and now we are excited to witness the nearly seamless translation of these important features into the clinic. The continued clinical advancement of D3S-001 reflects not only the innovation behind its design, but also the strength of these collaborations to bring meaningful therapies to patients worldwide."

About D3S-001

D3S-001 is a next-generation KRAS G12C inhibitor designed to achieve rapid and complete KRAS G12C target engagement. In preclinical investigations, D3S-001 has demonstrated high covalent potency, complete engagement of KRAS G12C at clinically relevant doses and CNS penetration properties. D3S-001 is currently in a Phase II global clinical trial in patients with advanced solid tumors harboring KRAS G12C mutations, including NSCLC, CRC, and other tumor types. Key publications:

D3S-001, a KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities. Cancer Discov (2024) 14 (9): 1675–1698.
D3S-001 in advanced solid tumors with KRAS G12C mutations. Nature Medicine (View Source)