On September 16, 2024 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage allogeneic cell therapy and genetic medicines company advancing differentiated non-viral treatments for patients with cancer and rare diseases, reported that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to P-BCMA-ALLO1, an investigational stem cell memory T cell (TSCM)-based allogeneic CAR-T cell therapy in Phase 1/1b clinical development for the treatment of patients with relapsed/refractory multiple myeloma (Press release, Poseida Therapeutics, SEP 16, 2024, View Source [SID1234646681]).

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RMAT designation includes all the benefits of the Fast Track and Breakthrough Therapy designation programs, including early interactions with the FDA. Poseida’s RMAT application was evaluated based on encouraging early data from its ongoing Phase 1 study of P-BCMA-ALLO1, which demonstrated P-BCMA-ALLO1’s potential to offer promising efficacy, safety profile and rapid ‘off-the-shelf’ patient access.

"The RMAT designation for P-BCMA-ALLO1, our lead program, is based on impressive early clinical data from our ongoing Phase 1 study and further validates its potential to address the unmet needs of patients with relapsed/refractory multiple myeloma," said Kristin Yarema, Ph.D., president and chief executive officer of Poseida Therapeutics. "Importantly, our data has shown clinical responses in very sick, refractory patients, including those that have received prior BCMA-targeted therapies. With both RMAT and Orphan Drug designations for P-BCMA-ALLO1, we look forward to working closely with the FDA as we continue to advance this next-generation, off-the shelf allogeneic CAR-T therapy, including the recently initiated Phase 1b portion of the trial."

The Company will report new clinical data from the P-BCMA-ALLO1 Phase 1 study in an oral session at the 21st International Myeloma Society Annual Meeting, which is being held in Rio de Janeiro from September 25-28, 2024. Additional clinical updates are planned for the second half of 2024, subject to coordination with Roche, which has a strategic collaboration with Poseida covering multiple investigational allogeneic CAR-T therapies targeting blood cancers, including P-BCMA-ALLO1.

The RMAT designation is a program under the 21st Century Cures Act that is intended to expedite the development and review of regenerative medicine therapies for serious or life-threatening diseases or conditions. A regenerative medicine therapy is eligible for RMAT designation if it is intended to treat, modify, reverse or cure a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the regenerative medicine therapy has the potential to address unmet medical needs for such disease or condition.

RMAT designation includes all Breakthrough Therapy designation features, including early interactions to discuss any potential surrogate or intermediate endpoints. RMATs may be eligible for accelerated approval based on previously agreed-upon surrogate or intermediate endpoints that are reasonably likely to predict long-term clinical benefit, or reliance upon data obtained from a meaningful number of sites, including through expansion to additional sites, as appropriate.

About P-BCMA-ALLO1
P-BCMA-ALLO1 is an allogeneic CAR-T product candidate licensed to Roche targeting B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma. This allogeneic program includes a VH-based binder that targets BCMA and clinical data presented at ASH (Free ASH Whitepaper) in December 2023 support the Company’s belief that T stem cell (TSCM)-rich allogeneic CAR-Ts have the potential to offer effective, safe, and reliable treatment addressing unmet needs in multiple myeloma. The FDA has granted P-BCMA-ALLO1 Regenerative Medicine Advanced Therapy (RMAT) designation for adult patients with relapsed/refractory multiple myeloma after three or more prior lines of therapies including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and anti-CD38 antibody in addition to Orphan Drug designation for multiple myeloma. Additional information about the Phase 1/1b study is available at www.clinicaltrials.gov using identifier: NCT04960579.

On September 16, 2024 Johnson & Johnson (NYSE: JNJ) reported interim data from the ongoing Phase 2 SunRISe-4 study showing neoadjuvant treatment with investigational TAR-200 plus cetrelimab (CET) achieved nearly double the pathological complete response (pCR) rate compared to CET alone in patients with muscle-invasive bladder cancer (MIBC) who are ineligible or refuse neoadjuvant platinum-based chemotherapy and scheduled for radical cystectomy (RC) (Press release, Johnson & Johnson, SEP 16, 2024, View Source [SID1234646680]). These data were featured as a late-breaking oral presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2024 Congress (Abstract #LBA84).

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"These findings from the SunRISe-4 study show for the first time that an intravesical treatment with TAR-200, combined with a systemic PD-1 inhibitor, could potentially result in a complete pathological response in a high proportion of patients, as well as allowing a tolerable approach," said Andrea Necchi, M.D., of Italy’s Vita-Salute San Raffaele University and the IRCCS San Raffaele Hospital and Scientific Institute and a presenting author of the study. "These preliminary findings show a potential for a future change in the local treatment of muscle-invasive bladder carcinoma using TAR-200."

In the interim analysis of the SunRISe-4 study, neoadjuvant TAR-200 plus CET (n=53) showed overall efficacy with a centrally confirmed pathologic complete response (pCR, [T0]) rate of 42 percent compared to 23 percent (95 percent CI, 28-56; 10-41, respectively) with CET alone (n=31) in patients with histologically proven, non-metastatic MIBC. The pathological overall response (pOR) rate (defined as the proportion of patients ≤ pT1) was 60 percent compared to 36 percent, respectively (CI 95 percent, 46-74; 19-55).1

In a subgroup analysis of patients with organ-confined disease (cT2), those treated with TAR-200 plus CET (n=40) showed a 48 percent pCR rate compared to 23 percent pCR with CET alone (n=26, 95 percent CI, 32-64; 9-44, respectively) and 68 percent were downstaged (≤ pT1) at the time of radical cystectomy, potentially improving surgical outcomes and reducing risk of recurrence.1

"With these promising results, TAR-200 plus cetrelimab as a neoadjuvant therapy before radical cystectomy could potentially alter how bladder cancer is treated," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Innovative Medicine, Johnson & Johnson. "This investigational innovative approach may offer a possible alternative for many patients who are not eligible for the current standard of pre-operative treatments."

Treatment-related adverse events (TRAEs) occurred in 72 percent of patients treated with TAR-200 combined with CET and 44 percent of patients treated with CET alone, with the majority being Grade 1-2. Nine percent of patients discontinued treatment with TAR-200 and eight percent discontinued treatment with CET in the combined treatment cohort due to TRAEs; no patients discontinued treatment due to TRAEs when treated with CET alone.1

Bladder cancer is the ninth most common cancer in the world.2 Although BCG immunotherapy has been accepted as the standard of care for nearly five decades, 30-40 percent of patients do not respond to BCG and experience disease recurrence or progression.3 In such scenarios, radical cystectomy (removal of the bladder and neighboring structures and organs) emerges as the primary treatment option. This major abdominal procedure requires a urinary diversion to be created to collect and store urine.4

TAR-200 is an investigational targeted releasing system designed to provide extended local release of gemcitabine into the bladder. It is installed in a physician’s office setting during a 2-3 minute procedure with no anesthesia. In December 2023, the FDA granted TAR-200 Breakthrough Therapy Designation (BTD) for the potential future treatment of patients with BCG-unresponsive HR-NMIBC, who are ineligible for or elected not to undergo radical cystectomy (surgical removal of the bladder).

About SunRISe-4
SunRISe-4 (NCT04919512) is an open-label, multicenter, randomized Phase 2 study assessing the efficacy and safety of neoadjuvant TAR-200 + cetrelimab (CET) (anti-programmed death-1 antibody) or neoadjuvant CET alone in patients with MIBC scheduled for RC who are ineligible for or refuse neoadjuvant platinum-based chemotherapy.

About TAR-200
TAR-200 is an investigational targeted releasing system, enabling extended release of gemcitabine into the bladder, increasing the amount of time the drug delivery system spends in the bladder and sustaining local drug exposure. The safety and efficacy of TAR-200 are being evaluated in Phase 2 and Phase 3 studies in patients with MIBC in SunRISe-2 and SunRISe-4, and NMIBC in SunRISe-1, SunRISe-3 and SunRISe-5.

About Cetrelimab
Cetrelimab is an investigational programmed cell death receptor-1 (PD-1) monoclonal antibody being studied for the treatment of bladder cancer, prostate cancer, melanoma, and multiple myeloma as part of a combination treatment. Cetrelimab is also being evaluated in multiple other combination regimens.

About Muscle-Invasive Bladder Cancer
Muscle-invasive bladder cancer (MIBC) is a severe form of bladder cancer where the tumor penetrates the muscular layer of the bladder wall, significantly increasing the risk of metastasis.5 Approximately 25 percent of bladder cancer cases are diagnosed as MIBC at the time of initial presentation.6 Early detection and timely intervention are crucial for managing MIBC, as delayed treatment can lead to poor prognosis.

On September 16, 2024 Medivir AB (Nasdaq Stockholm: MVIR), a pharmaceutical company focused on developing innovative treatments for cancer in areas of high unmet medical need, reported positive, mature data from its ongoing phase 1b / 2a study of fostroxacitabine bralpamide (fostrox) + Lenvima in advanced liver cancer (hepatocellular carcinoma/HCC) at the ESMO (Free ESMO Whitepaper) (European Society of Medical Oncology) Congress in Barcelona, Spain (Press release, Medivir, SEP 16, 2024, View Source;lenvima-confirm-promise-of-improved-outcomes-in-advanced-liver-cancer-detailed-and-mature-data-presented-at-esmo-302248817.html [SID1234646679]).

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Today’s ESMO (Free ESMO Whitepaper) update, poster number 986P, presented by Dr Hong Jae Chon on Monday September 16, shows promising duration of benefit with 19% of patients continuing treatment for more than a year and the longest running patient remaining on treatment for over 2 years, with sustained partial response. The patients in the study had disease control on fostrox + Lenvima independent if they benefitted from previous line of therapy, showing potential for all second-line patients to benefit from the combination. The safety and tolerability profile continues to be encouraging with no unexpected adverse events. While hematological adverse events were common, they were temporary in nature. Decreases in neutrophil & platelet counts showed a cyclic pattern with recovery before next cycle of treatment, enabling patients to remain on treatment long-term. Importantly, no patient experienced febrile neutropenia or low platelet count with bleeding and there were no fostrox-related serious adverse events.

Results come despite very poor prognosis for most second-line HCC patients today, with just 5–10% responding to current standard of care treatment, and a typical TTP of only 3–4 months.

Dr. Pia Baumann, Chief Medical Officer at Medivir, said:
– "With three patients still remaining on study treatment, all of whom treated for more than a year, this data-set is now quite mature. At a median follow-up of 10.5 months, fostrox + Lenvima have clearly shown promise of improved outcomes beyond current alternatives for second-line liver cancer patients. Fostrox is designed to only target tumor cells locally in the liver, without harming healthy cells. It is therefore reassuring to see the tolerability profile of fostrox enabling the combination of two highly potent treatments, fostrox + Lenvima, without compromising patient safety. Patients were able to stay on treatment long-term, which evidently contributes to the extended duration of benefit and a median time to progression of 10.9 months, substantially longer than previously seen in second-line liver cancer. It is with reinforced confidence we continue our preparations for the initiation of the planned phase 2b study comparing fostrox + Lenvima with Lenvima alone in a randomized setting to confirm the benefit of the combination."

Dr Hong Jae Chon, Professor at CHA Bundang Hospital in Korea, and investigator in the fostrox + Lenvima study, commented:
"Treatment outcomes have improved in first-line with the use of immunotherapy combinations, resulting in more patients fit enough to receive second-line treatment. But with no treatments approved in second-line after immunotherapy, there is a significant unmet medical need for new treatments options for these patients. The phase 1b/2a data for fostrox + Lenvima show highly encouraging clinical benefits for patients, indicating that when adding fostrox to Lenvima, efficacy is better than expected from Lenvima alone. It is especially encouraging that in addition to patients experiencing benefit for an extended period of time, patients also responded to the treatment independent of outcome in previous line of therapy. I look forward to evaluating the efficacy of fostrox plus Lenvima in a randomized, controlled trial."

The data are from Medivir’s ongoing phase 1b/2a open-label, multi-center, dose-escalation and dose-expansion study, evaluating the safety and efficacy of fostrox in combination with Lenvima in patients for whom current first- or second-line treatment has proven ineffective or is not tolerable.

HCC is the most common type of liver cancer, accounting for more than 80% of cases worldwide.2 There are approximately 660,000 patients diagnosed with HCC per year globally and current five-year survival is less than 20 percent3.

Medivir will host a webcast where Dr Chon and Dr Pia Baumann will present the data and answer questions. The webcast will take place Today, September 16, at 13.45 CET, and will be streamed via a link on the website: www.medivir.com/investors/presentations.

The poster and the presentation from the webcast will also be available on Medivir’s website after the presentation.

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.

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.