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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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 Checkpoint Therapeutics, Inc. ("Checkpoint") (Nasdaq: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported the presentation of longer-term data from its pivotal trial of cosibelimab, its anti-programmed death ligand-1 ("PD-L1") antibody, in locally advanced and metastatic cutaneous squamous cell carcinoma ("cSCC") during the European Society for Medical Oncology ("ESMO") Congress 2024, which is taking place in Barcelona, Spain, from September 13 to 17, 2024 (Press release, Checkpoint Therapeutics, SEP 16, 2024, View Source [SID1234646646]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Poster Presentation Title: Cosibelimab in Advanced Cutaneous Squamous Cell Carcinoma (CSCC): Longer-term Efficacy and Safety Results from Pivotal Study

"These longer-term results for cosibelimab presented at the ESMO (Free ESMO Whitepaper) Congress demonstrate a deepening of response over time, with higher objective response and complete response rates than initially observed at the primary analyses, and continue to expand the evidence supporting the efficacy and safety of cosibelimab as a potential new treatment for advanced cSCC," said James Oliviero, President and Chief Executive Officer of Checkpoint. "We look forward to our upcoming December 28, 2024, Prescription Drug User Fee Act ("PDUFA") goal date for our Biologics License Application for cosibelimab, and believe, if approved, cosibelimab’s dual mechanisms of action and safety profile may position the product, over time, as the preferred immunotherapy of U.S. oncologists."

Data highlights include:

Efficacy

With 16 months of additional follow-up since the primary analysis, cosibelimab demonstrated increasing objective response rates ("ORRs") and complete response rates per independent central review in 109 patients with advanced cSCC.
ORRs of 54.8% and 50.0% achieved in locally advanced and metastatic cSCC, with median follow-up durations of 24.1 and 29.3 months, respectively.
Results demonstrate a deepening of response over time, with complete response rates of 25.8% and 12.8% in locally advanced and metastatic cSCC, respectively.
Clinically meaningful durations of response ("DOR") were observed, with median DORs not yet reached in either group.
Safety

Overall, in 192 advanced cSCC patients treated with cosibelimab, a manageable safety profile was observed, with notable low rates of treatment-emergent adverse events ("TEAEs"), severe immune-related adverse events ("irAEs"), and treatment discontinuations.
3.6% of patients experienced an irAE assessed as grade 3, with no observed grade ≥4 irAEs.
No events of grade ≥3 pneumonitis, colitis, hepatitis, nephritis, or endocrinopathies.
Treatment discontinuation due to TEAEs, regardless of attribution, was observed in 12 patients (6.3%); the most common reason was COVID-19/COVID-19 pneumonia (1.6%).
A copy of the poster can be found on the Publications page of the Checkpoint Therapeutics website.

In December 2023, the U.S. Food and Drug Administration ("FDA") issued a complete response letter ("CRL") for the cosibelimab Biologics License Application ("BLA") for the treatment of patients with metastatic or locally advanced cSCC who are not candidates or curative surgery or radiation. The CRL only cited findings that arose during a multi-sponsor inspection of Checkpoint’s third-party contract manufacturing organization ("CMO") as approvability issues to address in a resubmission. In July 2024, Checkpoint announced it had completed a resubmission of the BLA to the FDA for cosibelimab to potentially address the approvability issues cited in the CRL. The resubmission was accepted by the FDA as a complete response and the FDA has set a PDUFA goal date of December 28, 2024.

About Cutaneous Squamous Cell Carcinoma (cSCC)
Cutaneous Squamous Cell Carcinoma is the second most common type of skin cancer in the United States, with an estimated annual incidence of approximately 1.8 million cases according to the Skin Cancer Foundation. Important risk factors for cSCC include chronic ultraviolet exposure and immunosuppressive conditions. While most cases are localized tumors amenable to curative resection, approximately 40,000 cases will become advanced, and an estimated 15,000 people will die from this disease each year. In addition to being a life-threatening disease, cSCC causes significant functional morbidities and cosmetic deformities based on tumors commonly arising in the head and neck region and invading blood vessels, nerves and vital organs such as the eye or ear. The immune-suppressed population represents a challenging target in the treatment of advanced cSCC, as they present with a more aggressive disease and with a higher risk of developing immune-related toxicities from checkpoint inhibitor treatment.

About Cosibelimab
Cosibelimab is a potential differentiated, high affinity, fully-human monoclonal antibody of IgG1 subtype that directly binds to PD-L1 and blocks the PD-L1 interaction with the programmed death receptor-1 ("PD-1") and B7.1 receptors. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response. Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies through sustained high tumor target occupancy of PD-L1 to reactivate an antitumor immune response and the additional potential benefit of a functional Fc domain capable of inducing antibody-dependent cellular cytotoxicity ("ADCC") for potential enhanced efficacy.

On September 16, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported that it has received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for patent application no. 18/535,108 entitled "Material and Method for Treating Cancer (Press release, UroGen Pharma, SEP 16, 2024, View Source [SID1234646663])."

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The allowed claims relate to the combination of UroGen’s RTGel technology with medac’s licensed proprietary lyophilized mitomycin formulation and cover the use of UroGen’s UGN-103 and UGN-104 development programs in the treatment of low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC) and low-grade upper tract urothelial cancer (LG-UTUC), respectively. The U.S. patent, once issued, will have an expiration date in December 2041.

"Allowance of this patent application strengthens our intellectual property position for our next-generation investigational programs for patients with urothelial cancers," said Liz Barrett, President and CEO of UroGen. "We believe that the combination of UroGen’s RTGel technology with medac’s patent-protected lyophilized mitomycin has the potential to provide advantages related to production, cost, supply, and product convenience for patients. Our vision remains to develop innovative medicines that advance the care of patients, and this patent allowance is a key element of our strategy to build a long-term growth company."

In January 2024, UroGen entered into a licensing and supply agreement with medac to develop UGN-103 for LG-IR-NMIBC and UGN-104 for LG-UTUC. In April 2024, the FDA accepted UroGen’s IND application for UGN-103 and the company is currently onboarding clinical sites for the study. The company anticipates commencing a similar study for UGN-104, which is expected in early 2025.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of LG-IR-NMIBC. Utilizing UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting by a trained healthcare professional. UroGen completed the NDA submission for UGN-102 in August 2024, ahead of schedule. UroGen anticipates potential FDA approval in early 2025 if the NDA is accepted for filing by the FDA and priority review is granted.

About UGN-103 and UGN-104

UGN-103 and UGN-104 are innovative mitomycin formulations in development by UroGen for the treatment of LG-IR-NMIBC and LG-UTUC, respectively. UGN-103 aims to streamline manufacturing and reconstitution processes while providing intellectual property coverage until December 2041; it utilizes UroGen’s RTGel technology for prolonged mitomycin exposure. UGN-104, also leveraging RTGel technology, is designed for treating low-grade upper tract urothelial cancer and is anticipated to enter Phase 3 trials in early 2025, offering a non-surgical treatment option with similar intellectual property protection.

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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 Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers, reported that the U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold on studies of azenosertib, the Company’s novel, selective, and orally bioavailable inhibitor of WEE1 (Press release, Zentalis Pharmaceuticals, SEP 16, 2024, View Source [SID1234649388]). The FDA has cleared the Company to resume enrollment in all ongoing azenosertib clinical studies with no changes in the clinical development plan. Zentalis will be working with clinical trial investigators to resume study activities across the azenosertib development program as quickly as possible.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are grateful to the FDA for their collaboration and review of our complete response package, which included a comprehensive safety assessment of the azenosertib program," said Kimberly Blackwell, M.D., Chief Executive Officer. "We are extremely pleased with the successful resolution of the partial clinical hold. Our confidence in the therapeutic index of azenosertib has been unwavering, and we continue to believe in the potential for this treatment to address unmet medical needs faced by people living with gynecologic malignancies."

At a corporate event later this year, Zentalis will present azenosertib monotherapy data and provide additional updates to azenosertib clinical development and other data presentation timelines. The Company remains on track to meet all previously disclosed data guidance for the remainder of 2024.

About Azenosertib
Azenosertib is a novel, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated in monotherapy and combination clinical studies in ovarian cancer and additional tumor types. WEE1 acts as a master regulator of the G1-S and G2-M cell cycle checkpoints, through negative regulation of both CDK1 and CDK2, to prevent replication of cells with damaged DNA. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage and leading to mitotic catastrophe and cancer cell death.