On September 16, 2024 PDS Biotechnology Corporation (Nasdaq: PDSB) ("PDS Biotech" or the "Company"), a late-stage immunotherapy company focused on transforming how the immune system targets and kills cancers and the development of infectious disease vaccines, reported updated data from the VERSATILE-002 trial evaluating Versamune HPV (formerly PDS0101) in combination with KEYTRUDA (pembrolizumab) as a first-line (1L) treatment for patients with HPV16-positive recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) (Press release, PDS Biotechnology, SEP 16, 2024, View Source [SID1234646661]). The data were presented during a poster session on September 14 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 in Barcelona, Spain.

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As of the latest data cut of the VERSATILE-002 single-arm, Phase 2 trial on May 17, 2024, Versamune HPV plus pembrolizumab continued to be well tolerated in this 1L R/M HPV16-positive HNSCC population. Enrollment in the trial (n=53) is complete, 10 patients remain on study treatment and 27 patients (including the 10 on treatment) continue to be followed for survival. Median patient follow-up is 16 months. The data demonstrated the following:

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Median Overall Survival (mOS) was 30 months with a lower 95% confidence interval of 19.7 months; Published mOS for pembrolizumab is 12-18 months1,2

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Objective Response Rate (ORR) of 36% (19/53); Published ORR for pembrolizumab is 19-25%1,2

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Disease Control Rate (DCR) is 77% (41/53)

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21% (11/53) of patients had deep tumor responses and shrinkage of 90-100%

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9% (5/53) of patients had a complete response

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Treatment-related adverse events of Grade ≥3 were seen in 9 patients (Grade 3, n=8 and Grade 4, n=1)

"The updated response data we presented at ESMO (Free ESMO Whitepaper) show the strong clinical activity and durability of Versamune HPV plus pembrolizumab," said Jared Weiss, M.D., Section Chief of Thoracic and Head/Neck Oncology, Professor of Medicine at the University of North Carolina, and principal investigator of the VERSATILE-002 clinical trial. "Continued evaluation shows the promise of this combination in improving survival for patients with HPV16-positive HNSCC."

A global, randomized, controlled Phase 3 clinical trial, VERSATILE-003, that will evaluate Versamune HPV plus pembrolizumab vs. pembrolizumab monotherapy as 1L treatment in patients with HPV16-positive R/M HNSCC with CPS ≥1 is planned to start this year.

"We’re encouraged to see that as the data from our VERSATILE-002 clinical trial have matured, responses continue to improve, suggesting durability of the Versamune HPV induced anti-tumor immune response," said Dr. Kirk Shepard, M.D., Chief Medical Officer of PDS Biotech. "The encouraging patient survival and clinical responses coupled with promising tolerability as seen in the VERSATILE-002 trial underscore our belief in the potential of the combination to be the first HPV-targeted immunotherapy for HNSCC, and a significant advancement in the treatment of the growing population of patients with HPV16-positive HNSCC. We are working toward initiating the VERSATILE-003 Phase 3 study this year."

Versamune HPV has been granted Fast Track designation by the FDA.

1.
Harrington K. et al. J Clin Oncol. 2022 ascopubs.org/journal/jco on October 11, 2022: DOI View Source

2.
Licitra L. et al. 2024, International Journal of Radiation Oncology Volume 118, Issue 5e2-e3April 01
No head-to-head studies have been performed comparing Versamune HPV with other treatments

On September 16, 2024 MEDSIR, a leading company dedicated to promoting independent clinical research in oncology internationally and part of Oncoclinicas & Co, the largest hospital group dedicated to cancer treatment in Latin America, reported this year in the congress of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper), held in Barcelona, presenting 12 new studies addressing different types of cancer (Press release, MedSIR, SEP 16, 2024, View Source [SID1234646677]).

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The studies presented by MEDSIR reflect its pivotal approach and commitment to innovation in personalized treatments, highlighting advances in prostate (ZZFIRST study), breast (ABIGAIL), thymic (PECATI) and lung (I3Lung.) cancers. Among these, the I3Lung study, funded by the European Union, integrates artificial intelligence models to optimize individualized treatments, reaffirming MEDSIR’s commitment to cutting-edge research. These studies underscore the strong commitment to significantly expand therapeutic options for patients facing complex and difficult-to-treat cancers.

Among the most relevant studies is ABIGAIL, in patients with HR+/HER2- advanced breast cancer and poor prognosis criteria. Its objective is to provide consistent evidence that the treatment strategy with abemaciclib (a CDK4/6 inhibitor) in combination with endocrine therapy as first-line treatment in advanced breast cancer is not inferior to paclitaxel (the standard chemotherapy commonly used in this type of patient) in terms of overall response rate and safety during the first 12 weeks. The aim of this study is to provide hope to patients by offering a chemotherapy-free treatment option. The overall response rate at 12 weeks was markedly better in the group treated with the combination of abemaciclib and endocrine therapy (59%) compared to the group receiving chemotherapy (40%).

"The data from the ABIGAIL study are a crucial step forward for patients with HR+/HER2- advanced breast cancer. The possibility of offering a chemotherapy-free alternative not only improves quality of life, but also offers new perspectives for these patients with poor prognostic criteria. This study reinforces our commitment to finding more effective and less aggressive therapeutic solutions for those who need it most," adds Dr. Juan de la Haba, principal investigator of the study and oncologist at the Reina Sofia University Hospital in Córdoba (Spain).

Another highlight of the congress was the oral presentation of the PECATI study, aimed at patients with thymic tumors, a rare disease that includes thymomas and thymic carcinomas. To date, there have been no standard treatments for metastatic thymic carcinomas beyond chemotherapy, and therapeutic advances in this field have been scarce due to the low prevalence of the disease. The study, an international initiative conducted in 10 hospitals in Spain, Italy and France, evaluated the efficacy of combining two drugs, lenvatinib and pembrolizumab (immunotherapy treatment), in patients with advanced and previously treated thymic tumors. The results were positive, as 88% of the patients had no disease progression during the first 5 months of treatment, and in more than half of the patients (62%) the disease had not progressed at 12 months after the start of treatment.

These findings highlight the potential efficacy of this combination therapy and could be considered a future gold standard treatment for this pathology. "These results are truly promising. Thanks to research, we are opening up new therapeutic possibilities that make a difference in patients’ lives. While research is essential to improve treatments in any type of cancer, it becomes even more relevant in rare tumors such as thymomas, where treatment options are more limited," says Dr. Jordi Remon, principal investigator of the study and medical oncologist at the Institut Gustave Roussy in Paris, France.

These positive results not only reflect a significant advance in the treatment of patients with limited therapeutic options, but also consolidate the importance of innovation and the integration of new treatments in the optimization of therapeutic regimens. MEDSIR is thus positioned at the forefront of oncology research, pushing the frontier of scientific knowledge towards new therapeutic possibilities.

Advancing research in the area of brain metastases

In addition, the company led a symposium on brain metastasis (September 14th), which addressed the essential role of Investigator-Initiated Trials (IITs) and pharmaceutical industry-sponsored trials in revolutionizing our understanding and treatment strategies for one of the biggest challenges, brain metastasis. This remains a critical unmet need, particularly in solid tumors such as lung, breast, and skin cancers.

As a tough challenge in oncology, brain metastasis requires innovative solutions and collaborative efforts. The event, named MEDTalks, featured chairs like Prof. Antonio Llombart, MEDSIR Senior Scientific Lead, and Prof. Mathias Preusser, Head of the Clinical Division of Oncology at the Medical University of Vienna.

During a 360° overview of the biology, pathology, and development of brain metastases, along with recent advancements in systemic management, speakers focused on groundbreaking new drugs, such as Antibody-Drug Conjugates (ADCs) and radio-ligands, delving into the emerging field and potential of theranostics in oncology.

On September 16, 2024 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CANF), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address oncological and inflammatory diseases, reported that it received approval from the Israeli Ministry of Health (MoH) to conduct Phase IIa clinical trial with orally-administered Namodenoson in the treatment of pancreatic carcinoma (Press release, Can-Fite BioPharma, SEP 16, 2024, View Source [SID1234646645]).

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"We are very much encouraged by the excellent data in the pre-clinical studies demonstrating the impressive anti-cancer effect of namodenoson and definitive molecular mechanism of action against pancreatic carcinoma," stated Dr. Fishman, Can-Fite’s Chief Scientific Officer and Executive Chairman. "We are very keen to initiate the study in this devastating disease and are pleased with the regulatory approval of the Israeli MOH. We do hope that as we have shown efficacy in patients with advanced liver cancer studies, we will be able to demonstrate safety and efficacy in the pancreatic cancer patient population."

The Phase IIa is a multicenter open-label trial in patients with advanced pancreatic adenocarcinoma whose disease has progressed on at least 1st-line therapy. The trial will evaluate the safety, clinical activity, and pharmacokinetics (PK) of Namodenoson in this patient population. All patients will receive oral Namodenoson 25 mg, administered twice daily for consecutive 28-day cycles. Patients will be evaluated regularly for safety. Approximately 20 evaluable patients will be enrolled. The primary objective of this trial is to characterize the safety profile of Namodenoson and the secondary objective is to evaluate the clinical activity as determined by the Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), Progression-Free Survival (PFS), Disease Control Rate (DCR), Duration of Response (DoR), and Overall Survival (OS).

The study will be conducted by Dr. Stemmer, a leading key opinion leader, at the Institute of Oncology, Rabin Medical Center, Israel and by Dr. Al Mutar from the UT Southwestern Medical Center in the US.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson was evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.

On September 16, 2024 Ribometrix, a biotechnology company developing small molecule therapeutics that modulate RNA biology, reported the latest data from its eIF4E program at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, taking place in Barcelona, Spain, September 13-17 (Press release, Ribometrix, SEP 16, 2024, View Source [SID1234646662]). The poster presentation reviews in vitro and in vivo studies of a small molecule eIF4E inhibitor, RBX-6610, as a potential treatment for KRASG12C mutant non-small cell lung cancer (NSCLC). Acquired resistance is observed in most patients treated with the two approved therapies for KRASG12C mutant NSCLC, creating a significant opportunity for a therapy that re-sensitizes tumors to KRAS inhibition. Ribometrix’s data supports RBX-6610’s ability to deliver this mechanism in combination with the approved therapies.

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"In less than three years, Ribometrix has advanced its eIF4E program from concept to a lead molecule that has just completed non-GLP toxicology studies," stated Michael Solomon, CEO of Ribometrix, Inc. "The program is a testament to Ribometrix drug discovery capabilities, and the commitment and professionalism of the Ribometrix team. We look forward to moving this program forward into the clinic in collaboration with a partner who shares our vision of its potential to benefit patients, via its novel mechanism of action."

"These data further evidence the broad potential of eIF4E inhibition in multiple tumor types, particularly in combination as a re-sensitizing agent. We have further validated the mechanism of action and characterized the synergistic benefit of RBX-6610, our most advanced eIF4E inhibitor," said Jessica Sorrentino, Ph.D., SVP of Translational Medicine. "RBX-6610 is progressing towards the clinic and we see significant promise for its inclusion with the standard-of-care for both naïve and treatment resistant NSCLC patients, especially whose tumors have KRAS mutations."

Key highlights:

RBX-6610 demonstrated consistent anti-proliferative effects in KRASG12C mutant tumor cell lines, in both treatment-naïve lines and those with acquired resistance.
Additionally, the combined in vitro effects of co-treatment of RBX-6610 with KRAS inhibitors were synergistic, such that the proliferative inhibitory effects were greater than the sum of either treatment alone. Mechanistically, this was due to an induction of apoptosis, specific to co-treatment in treatment-naïve tumor cells as well as cells resistant to KRAS inhibitors. This synergistic phenotype was observed with both approved KRAS inhibitors, as well as investigational RAS inhibitors.
Daily oral RBX-6610 monotherapy led to substantial tumor growth inhibition in both treatment naïve and resistant KRASG12C NSCLC xenograft model (75% vs 71% TGI, respectively), corroborating the anti-proliferative effects seen in vitro.
In combination with sotorasib, an approved KRAS inhibitor, daily oral treatment with RBX-6610 led to significant tumor regression and improved survival in both the treatment-naïve and sotorasib resistant setting (34% and 49% mean tumor regression respectively). No toxicity was observed in up to 35 days of daily oral treatment across all cohorts.
In vitro data demonstrated improved selectivity of cap dependent translation inhibition by RBX-6610 relative to other translation inhibitors including zotatifin, an eIF4A inhibitor.
Ribometrix continues to generate data demonstrating the multi-tumor therapeutic potential of eIF4E inhibition. Studies in melanoma and breast cancer were presented at the Society for Melanoma Research and the San Antonio Breast Cancer Symposium in 2023, and data across melanoma, colorectal, breast, and non-small cell lung cancer were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in 2024. Data have repeatedly included support for both monotherapy and combination regimens as well as the potential to re-sensitize to standard-of-care treatments.

The ESMO (Free ESMO Whitepaper) poster is now available to view on the "Publications" page of Ribometrix’s website.

About eIF4E

Eukaryotic translation initiation factor 4E (eIF4E) is a crucial regulatory component of mRNA translation and well-documented driver of oncogenesis. Clinically, eIF4E activity is elevated in many tumor indications and it is typically associated with poor prognosis. Targeting eIF4E has the potential to enhance anti-cancer activity when given in combination with standard-of-care. Additionally, eIF4E inhibition has the potential to overcome drug resistance and re-sensitize tumors to anti-cancer therapies. Based on substantial external and in-house data, Ribometrix is developing eIF4E inhibitors as a promising combination therapy approach and treatment for treatment-resistant tumors.

On September 16, 2024 Akeso (9926.HK) reported the phase 2 results from its ivonescimab in combination with chemotherapy as a first-line (1L) treatment for triple-negative breast cancer (TNBC) at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Conference (Press release, Akeso Biopharma, SEP 16, 2024, View Source [SID1234646678]). The preliminary data, with only a 10-month median follow-up, revealed that the ivonescimab combination regimen demonstrated excellent efficacy and a favorable safety profile in 1L TNBC. Professor Wang Xiaojia from Zhejiang Provincial Cancer Hospital, a co-primary investigator of the study, presented the findings orally at the conference.

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As of May 31, 2024, a total of 30 patients with locally advanced unresectable or metastatic TNBC were enrolled. 80% of patients had a PD-L1 combined positive score (CPS) <10, and 60% of patients had previously received taxane-based neoadjuvant or adjuvant therapy (a proportion higher than that observed in similar studies involving targeted drugs).

Although the follow-up period is relatively short and the data are not yet mature, the study still demonstrates that the ivonescimab combination regimen demonstrates excellent progression-free survival (PFS) benefits for TNBC patients, with safety consistent with previous ivonescimab-related studies.

Ivonescimab combination regimen demonstrated high efficacy in tumor response and disease control, with an objective response rate (ORR) of 72.4% and a disease control rate (DCR) of 100%, including a complete response (CR) rate of 6.9%.
As of the latest update, five additional patients have achieved partial response (PR) (Among them, four newly evaluable patients all achieved a PR, and one patient who previouly had stable disease also achieved a PR ), leading to an adjusted ORR of approximately 78.8% and DCR of 100%.
Ivonescimab combination regimen showed a promising trend towards improved long-term survival benefits, with a median progression-free survival (PFS) of 9.3 months (6.24 months -NE), and a 6-month PFS rate of 73.3%.
In the PD-L1 CPS≥10 population, the ORR was 83.3%, and the median PFS was not yet reached.
In the PD-L1 CPS <1 population, the ORR was 86.7%, with a median PFS of 9.3 months (5.26 months-NE).
As of the latest update, two additional patients in the PD-L1 CPS <1 group have achieved PR, resulting in an adjusted ORR of 88.2%.
In the PD-L1 CPS <10 population, the ORR was 69.6%, with a median PFS of 9.3 months (5.55 months-NE).
As of the latest update, five additional patients in this group have achieved PR, leading to an adjusted ORR of approximately 77.8%.
Ivonescimab combined with chemotherapy as a first-line treatment for TNBC exhibited an acceptable safety profile. The most common treatment-related adverse events (TRAEs) were predominantly grade 1-2 and manageable, consistent with previous studies. There were no TRAEs that led to permanent treatment discontinuation or death.