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Zentalis Announces Presentation of Positive Phase 1b Data Demonstrating Durable Responses and Favorable Safety Profile of Azenosertib in Combination with Chemotherapy at the 2023 ASCO Annual Meeting

On May 26, 2023 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 positive data from the Phase 1b trial of azenosertib, the Company’s potentially first-in-class WEE1 inhibitor, in combination with chemotherapy in patients with platinum-resistant ovarian cancer (Press release, Zentalis Pharmaceuticals, MAY 26, 2023, View Source [SID1234632151]). Azenosertib was well tolerated in combination with multiple types of chemotherapy and demonstrated encouraging clinical activity, with noteworthy improvements in objective response rates (ORRs) and median progression free survival (mPFS) in all patients, especially those with Cyclin E1+ tumors, a subgroup recognized to have a poor prognosis and be refractory to chemotherapy. Results will be presented in a poster discussion session at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting on June 5th (Abstract #5513).

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"Azenosertib is emerging as a very promising clinical candidate, with demonstrated anti-tumor activity in difficult-to-treat tumor types when used in combination with standard chemotherapy regimens," said Kimberly Blackwell, M.D., Chief Executive Officer of Zentalis. "The addition of azenosertib increased ORRs and mPFS over those observed historically with chemotherapy alone, or compared to adavosertib in combination with chemotherapy. We are very encouraged by our robust chemotherapy combination data, particularly the strong efficacy and tolerability results when dosing azenosertib intermittently. These data provide a compelling rationale to advance azenosertib into a registrational study in combination with either carboplatin or paclitaxel in Cyclin E1+ ovarian cancer. We look forward to providing additional insights into our azenosertib clinical programs and the franchise potential we see for this product candidate during our June 6 investor webcast."

Efficacy and Safety Results:

A total of 115 patients were enrolled in the study across all chemotherapy combination groups. At the data cut-off of April 10, 2023, 94 were efficacy evaluable. Across all dosing schedules, azenosertib plus paclitaxel demonstrated the highest ORR of 50.0% (mPFS of 7.4m), followed by an ORR of 38.5% (mPFS of 8.3m) for azenosertib plus gemcitabine. Azenosertib plus carboplatin demonstrated an ORR of 35.7% (mPFS of 10.4m), and azenosertib plus PLD demonstrated an ORR of 19.4% (mPFS of 6.3m).

A total of 82 response-evaluable patients had available Cyclin E1 expression data by immunohistochemistry (IHC). Cyclin E1+ status (H-score >50) was associated with a superior ORR and a longer mPFS across the total patient population (ORR of 40.0% vs 8.3%; mPFS of 9.86 vs 3.25 months, HR = 0.37; P = 0.0078), showcasing the potential synergy of WEE1 inhibition with chemotherapy in this patient population.

Overall, the tolerability of azenosertib dosed intermittently in combination with either paclitaxel or carboplatin compares favorably to historical data from standard of care chemotherapy doublets of either paclitaxel-carboplatin or PLD-carboplatin. Frequent Grade ≥3 treatment-related adverse events (%) across all azenosertib intermittent dosing groups were thrombocytopenia (27.5%), neutropenia (25.5%), anemia (15.7%), and fatigue (9.8%). A recommended Phase 2 dose was determined for each of the azenosertib combinations with paclitaxel, carboplatin, and PLD.
Based on these results, the Company is planning to initiate a Phase 3 study comparing azenosertib dosed intermittently in combination with either carboplatin or paclitaxel in patients with Cyclin E1+ platinum-sensitive ovarian cancer. The Company expects to initiate the Phase 3 study in the first quarter of 2024.
"The results thus far for azenosertib in combination with chemotherapy are very promising, as there remains high unmet need in this patient population, particularly patients with Cyclin E1+ tumors who historically have not responded well to chemotherapy," said Joyce Liu, M.D., M.P.H., Associate Chief and Director of Clinical Research for the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute. "I look forward to continuing to work with the Zentalis team to advance azenosertib in the clinic and, if approved, ultimately into medical practice as an important and novel treatment option for platinum-sensitive ovarian cancer patients."
Premal H. Thaker, M.D., Professor of Obstetrics and Gynecology, Director of Gynecological Oncology Clinical Research, Division of Gynecologic Oncology, Washington University School of Medicine, and an investigator on the study added, "The data for azenosertib in combination with chemotherapy are increasingly robust and encouraging. Moreover, the enrichment of patients by Cyclin E1+ status provides a compelling strategy for future clinical trials. I look forward to the initiation of a study examining the role of azenosertib in combination with chemotherapy in earlier lines of therapy."

The Company will host a webcast on Tuesday, June 6, 2023 at 8:00 a.m. ET to provide a clinical update, including an overview of the ASCO (Free ASCO Whitepaper) data, as well as safety, pharmacology and efficacy results for azenosertib as a monotherapy, and plans for future development of azenosertib as a monotherapy and in combination with chemotherapy. The corporate webcast will be accessible via the Investors page of Zentalis’ website, www.zentalis.com. The archived webcast and presentation will be available on the Company’s website after the event.

ASCO Presentation Details:
Poster Title: Correlation of Cyclin E1 expression and clinical outcomes in a Phase 1b dose-escalation study of Azenosertib (ZN-c3), a WEE1 inhibitor, in combination with chemotherapy in patients with platinum-resistant or refractory (R/R) epithelial ovarian, peritoneal, or fallopian tube cancer
Presenter: Dr. Liu, M.D., M.P.H., Associate Chief and Director of Clinical Research for the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute.
Session Title: Gynecologic Cancer

Session Date and Time: Monday, June 5, 2023, 1:15 – 4:15 p.m. CT
Location: Hall A
Poster Board Number: 208
Poster Discussion Session Date and Time: Monday, June 5, 2023, 4:30 – 6:00 p.m. CT
Location: S100bc
Abstract Presentation Number: 5513

A video summary of the poster by Dr. Liu will be available on the ASCO (Free ASCO Whitepaper) virtual platform.
Once presented, the poster can be found on the Company’s website using this link.

About Azenosertib
Azenosertib is a potentially first-in-class and best-in-class small molecule WEE1 inhibitor in development for the treatment of cancer. Inhibition of WEE1, a DNA damage response kinase, drives cancer cells into mitosis without being able to repair damaged DNA, resulting in cell death. Currently, there are no FDA-approved WEE1 inhibitors, and azenosertib has been designed for superior selectivity and pharmacokinetic properties. Azenosertib is being developed in therapeutic areas of high unmet need and is being evaluated as a monotherapy, in combination with chemotherapy, and in combination with molecularly targeted agents.

Y-mAbs Announces Presentation of Naxitamab Data at ASCO

On May 26, 2023 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that a poster presentation featuring interim clinical data on naxitamab, a recombinant, humanized anti-GD2 monoclonal antibody, in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF") will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting to be held June 2-6, 2023, in Chicago, Illinois (Press release, Y-mAbs Therapeutics, MAY 26, 2023, View Source [SID1234632150]).

Patients with high-risk neuroblastoma ("HR-NB") commonly develop metastases in the bone and/or bone marrow. Approximately 15% of HR-NB patients are refractory to induction therapy and approximately 50% will relapse. The ongoing Phase 2 Trial 201 (NCT03363373) evaluates naxitamab in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF") in patients with relapsed or refractory HR-NB with residual disease limited to bone and/or bone marrow. Patients with disease in soft tissues or actively progressing disease were excluded from the trial.

Curie Score ("CS") is a semi-quantitative scoring system used to assess the extent of bone metastases and treatment response. Higher CS indicates more extensive bone involvement and may suggest a poorer prognosis.

An interim analysis of Trial 201 (data cutoff December 31, 2021) included 52 patients in the efficacy group and 74 patients in the safety group. The efficacy analyses included the overall response rate (ORR; complete response or partial response) and the reduction in CS by baseline disease status, i.e., refractory or relapsed disease. Clinically meaningful ORRs and reductions in CS were seen in patients regardless of baseline disease status. The ORR was 58% in patients with refractory disease and 42% in patients with relapsed disease. Furthermore, from a mean baseline CS of 5.5 and 5.7 in the refractory and relapsed subgroups (range 1-20 across the two subgroups), the mean change to end of naxitamab treatment was -4.2 and -1.2, respectively. Maximum reductions in CS for relapsed and refractory subgroups were -17 and -18, respectively. Overall, the most common naxitamab related serious adverse events were hypotension, pain, urticaria, and bronchospasm. Baseline CS did not affect the safety profile of naxitamab. Patients with refractory disease had a lower frequency of serious naxitamab related adverse events compared to patients with relapsed disease.

Naxitamab was licensed by the Company from Memorial Sloan Kettering ("MSK"). MSK has institutional financial interests in the compound.

About DANYELZA (naxitamab-gqgk)

DANYELZA (naxitamab-gqgk) is indicated, in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF"), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. This indication was approved in the United States by the FDA under accelerated approval based on overall response rate and duration of response. Continued approval for this indication is contingent upon verification and description of clinical benefits in a confirmatory trial. DANYELZA includes a Boxed Warning for serious infusion-related reactions, such as cardiac arrest and anaphylaxis, and neurotoxicity, such as severe neuropathic pain and transverse myelitis. See full Prescribing Information (View Source) for complete Boxed Warning and other important safety information.

xCures showcases the power of its real-time clinical data platform at ASCO Annual Meeting 2023

On May 26, 2023 xCures, a healthcare technology company, reported its participation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2023, to be held from June 02 – 06, 2023, at McCormick Place, Chicago, IL USA (Press release, xCures, MAY 26, 2023, View Source [SID1234632149]).

The two abstracts accepted showcase the capabilities of its real-time clinical data platform to support patient care. The abstracts illustrate the platform´s enhanced longitudinal nationwide data beyond existing traditional retrospective real-world data (RWD) and how its platform can prospectively track clinical outcomes for (rare) cancer patient populations and structure clinical data for decision support.

"Access to real-time, longitudinal, uninterrupted clinical data offers an unparalleled capacity to extract insights from patient medical records," said Tim Stuhlmiller, Vice President of Scientific and Medical Affairs at xCures, "these abstracts showcase our ability to utilize real-world data to improve patient care today, rather than 2-5 years from now."

The xCures data platform, powered by a connection to the health information exchange and structured FHIR and CCDA data direct from institutional EMRs, has enabled a nationwide analysis of glioblastoma therapeutic combinations.

Under the guidance of Dr. Michael Castro of the Beverly Hills Cancer Center, a potentially practice-changing detrimental effect of proton pump inhibitors in glioblastoma was unveiled. This data is critical since up to 60% of brain cancer patients are prescribed these drugs, which could easily be exchanged for drugs with a different mechanism of action.

In a second abstract, xCures supports Dr. Paul Kent and the FibroFighters advocacy group to implement a multidisciplinary, international tumor board for fibrolamellar carcinoma, a rare adolescent and young adult cancer.

This tumor board is one of the world´s few international virtual tumor boards and the first ever for fibrolamellar carcinoma, offering patients a free consultation from leading experts. The xCures outcomes database provides actionable clinical data to guide decision-making in the tumor board. In addition, the platform collects outcomes prospectively to close the learning loop and improve future recommendations of the board.

Attendees of the ASCO (Free ASCO Whitepaper) Annual Meeting are encouraged to find Tim Stuhlmiller, Mark Shapiro, and Max Goldstein from xCures, who can provide in-depth insights, discuss potential collaborations, and showcase case studies from the platform´s implementation.

The abstracts presented:

Use of proton pump inhibitors (PPI) in glioblastoma (GBM) and relationship to overall survival in a national real-world evidence (RWE) database.

Authors: Michael Castro, Jameson Quinn, Asher Wasserman, Mark Shapiro, Timothy Stuhlmiller, Santosh Kesari

View Source

and,

Clinical utility of an international multidisciplinary virtual tumor board for fibrolamellar carcinoma.

Authors: Paul Kent, Jordan Tasse, Erik Schadde, Tomoaki Kato, Abhinav Humar, Oliver Fisher, Matthew Dixon, Darrell Yamashiro, Albert Cornelius, Nelson Royall, Thomas Kim, Julie Friedland, Timothy Stuhlmiller, Alaa Awawda, Alanis Sabates, Mark Shapiro, Jessica Ellison, Tom Stockwell

View Source

PharmaMar announces abstracts to be presented at ASCO 2023

On May 26, 2023 PharmaMar (MSE:PHM) reported that the Company and its partners will present seven new abstracts from several clinical trials with Zepzelca (lurbinectedin) and Yondelis (trabectedin) at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), to be held on June 2-6, 2023, both virtually and in situ in Chicago, USA (Press release, PharmaMar, MAY 26, 2023, View Source [SID1234632146]).

The studies to be presented at the congress include two oral presentations with two PharmaMar compounds. With the abstract entitled: "Efficacy of combination lurbinectedin (LURBI) + doxorubicin (DOX) from the phase 1B soft-tissue sarcoma (STS) lead-in to a randomized phase 2 trial in leiomyosarcoma (LMS)", Gregory Cote, MD, PhD, medical oncologist at Massachusetts General Hospital, will present updated efficacy and tolerability data on the combination of lurbinectedin with doxorubicin from the phase 1B soft-tissue sarcoma study leading into a randomized phase II trial in leiomyosarcoma (LMS).

Peter Reichardt, MD, Physician-in-Chief of the Interdisciplinary Oncology Clinic HELIOS Klinikum Berlin-Buch, will present the abstract entitled: "Efficacy and safety of nivolumab and trabectedin in pretreated patients with advanced soft tissue sarcomas (STS): Results of a phase II trial of the German Interdisciplinary Sarcoma Group (GISG-15, NitraSarc)", in which he will present efficacy and safety data of trabectedin plus nivolumab as second-line treatment for patients with metastatic or inoperable soft tissue sarcoma, previously treated with anthracyclines. The study confirms the activity of trabectedin plus nivolumab, particularly in patients with lipo- or leiomyosarcomas, suggesting synergistic activity. In addition, the safety of trabectedin and nivolumab was consistent with the safety profiles of each drug separately, with no new findings relevant to the combination.

All ASCO (Free ASCO Whitepaper) poster presentations are available on request to registered participants for 180 days from May 26, 2023: View Source

Highlighted studies at ASCO (Free ASCO Whitepaper) 2023

PRODUCT TITLE LEAD AUTHOR ABSTRACT
Zepzelca (lurbinectedin) Efficacy of combination lurbinectedin (LURBI) + doxorubicin (DOX) from the phase 1B soft-tissue sarcoma (STS) lead-in to a randomized phase 2 trial in leiomyosarcoma (LMS) Gregory Cote ABSTRACT: 11507 SESSION TYPE: Oral Abstract Session S100a DATE: June 5, 2023 11:30 – 14:30 GMT-5
Zepzelca (lurbinectedin) Efficacy and safety of lurbinectedin in elderly patients with relapsed SCLC Sophie Cousin ABSTRACT: 8591 SESSION TYPE: Poster Session POSTER: 218 DATE: June 4, 2023 8:00 – 11:00 GMT-5
Zepzelca (lurbinectedin) A phase III study of lurbinectedin alone or in combination with irinotecan vs investigator’s choice (topotecan or irinotecan) in patients with relapsed small cell lung cancer (SCLC; LAGOON trial) Benjamin Besse ABSTRACT: TPS8613 SESSION TYPE: Poster Session POSTER: 233a DATE: June 4, 2023 8:00 – 11:00 GMT-5
Zepzelca (lurbinectedin) IFCT-2105 lurbiclin real-world effectiveness and treatment sequences in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC) who received lurbinectedin as part of the French Early Access Program (EAP-ATU) Nicolas Girard ABSTRACT: 8584 SESSION TYPE: Poster Session POSTER: 211 DATE: June 4, 2023 8:00 – 11:00 GMT-5
Yondelis (trabectedin) Efficacy and safety of nivolumab and trabectedin in pretreated patients with advanced soft tissue sarcomas (STS): Results of a phase II trial of the German Interdisciplinary Sarcoma Group (GISG-15, NitraSarc) Peter Reichardt ABSTRACT: 11500 SESSION TYPE: Oral Abstract Session S100a DATE: June 5, 2023 11:30 – 14:30 GMT-5
Yondelis (trabectedin) SARC037: Results of phase I study of trabectedin given as a 1-hour (h) infusion in combination with low dose irinotecan in relapsed/refractory Ewing sarcoma (ES) Patrick Grohar ABSTRACT: 11519 SESSION TYPE: Poster Discussion Session POSTER: 453 DATE: June 3, 2023 16:30 – 18:00 GMT-5
Yondelis (trabectedin) Trabectedin (T) versus adriamycin plus dacarbazine (A-DA) in advanced solitary fibrous tumor (SFT): Results from a phase II randomised clinical study (STRADA) Silvia Stacchiotti ABSTRACT: 11571 SESSION TYPE: Poster Session POSTER: 505 DATE: June, 2023 13:15 – 16:15 GMT-5

Iovance Biotherapeutics Announces U.S. Food and Drug Administration Acceptance of the Biologics License Application of Lifileucel for the Treatment of Advanced Melanoma

On May 26, 2023 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported that the U.S. Food and Drug Administration (FDA) accepted its Biologics License Application (BLA) for lifileucel for patients with advanced melanoma (Press release, Iovance Biotherapeutics, MAY 26, 2023, View Source [SID1234632145]). The FDA granted lifileucel Priority Review and assigned November 25, 2023 as the target action date for a decision under the Prescription Drug User Fee Act (PDUFA). The FDA is not currently planning to hold an advisory committee meeting to discuss this application and, after a preliminary review, has not at this time identified any potential review issues.

Lifileucel is a TIL therapy intended for patients with advanced melanoma who progressed on or after prior anti-PD-1/L1 therapy and targeted therapy, where applicable. There are no FDA approved therapies in this treatment setting. Under the FDA’s guidance, Priority Review allows for an six-month review from the time of BLA acceptance for treatments that, if approved, are substantially safer or more effective than standard of care therapies. The FDA also previously granted a Regenerative Medicine Advanced Therapy (RMAT) designation for lifileucel in advanced melanoma.

Frederick Vogt, Ph.D., J.D., Interim President and Chief Executive Officer of Iovance, stated, "The BLA acceptance is a significant milestone in our mission to deliver lifileucel as the first individualized, one-time cell therapy for a solid tumor. The FDA’s commitment to a six-month Priority Review validates the unmet need and urgency for new treatment options for patients with advanced melanoma who have progressed on or after standard of care therapies. I am grateful for the patients and physicians who took part in all our clinical trials, as well as the Iovance team for their outstanding work on our first BLA filing. We look forward to continuing our collaboration with the FDA during the BLA review cycle, while continuing to execute our pre-commercialization activities and advancing our robust TIL pipeline."

The BLA submission for lifileucel is supported by positive data from the C-144-01 clinical trial in patients with advanced melanoma who progressed on or after prior anti-PD-1/L1 therapy and targeted therapy, where applicable. If lifileucel receives accelerated approval, the randomized Phase 3 TILVANCE-301 trial in frontline advanced melanoma can serve as the confirmatory study to support full approval. TILVANCE-301 is expected to be well underway at the time of approval.