On October 23, 2023 Quince Therapeutics, Inc. (Nasdaq: QNCX), a late-stage biotechnology company developing an innovative drug delivery technology that leverages a patient’s own biology to deliver rare disease therapeutics, reported the successful completion of its acquisition of EryDel S.p.A., a privately-held, late-stage biotech company (Press release, Quince Therapeutics, OCT 23, 2023, View Source [SID1234636259]). Quince’s newly acquired Phase 3 lead asset, EryDex, targets a rare neurodegenerative disease, Ataxia-Telangiectasia (A-T). Currently, there are no approved treatments for A-T and the market represents a $1+ billion estimated peak sales opportunity globally. EryDex utilizes a highly differentiated and proprietary technology platform for autologous intracellular drug encapsulation (AIDE), which is designed to optimize the biodistribution of dexamethasone sodium phosphate (DSP; a pro-drug) by using an A-T patient’s own red blood cells to deliver the sustained therapeutic over a once monthly treatment period.

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"The successful closing of the EryDel acquisition is an exciting step forward in fulfilling our vision to build a leading rare disease biotechnology company," said Dirk Thye, M.D., Quince’s Chief Executive Officer. "We are dedicated to developing treatments utilizing our proprietary AIDE technology platform that hold the potential to help children and families affected by rare and debilitating diseases such as A-T. Quince’s priority is to advance the Phase 3 clinical trial of EryDex to evaluate its safety and efficacy for the treatment of A-T, then expand our development efforts into other potential indications that leverage our proprietary AIDE technology platform."

Quince is well-capitalized into 2026 and intends to focus its development expertise and financial resources toward advancing a single global Phase 3 NEAT (Neurologic Effects of EryDex on Subjects with A-T) clinical trial, which is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the neurological effects of EryDex on patients with A-T. Enrollment for the Phase 3 NEAT trial is expected to begin in the second quarter of 2024. The company plans to enroll approximately 86 A-T patients aged six to nine years-old and approximately 20 additional A-T patients aged 10 years or older. This pivotal clinical trial will be conducted under a Special Protocol Assessment (SPA) that has been agreed with the U.S. Food & Drug Administration (FDA), which should allow for the submission of a New Drug Application (NDA) following completion of this single study, assuming positive results.

Quince’s integrated senior leadership team holds extensive development, clinical, regulatory, and commercial expertise, and includes:

Dirk Thye, M.D. – Chief Executive Officer and member of Quince’s Board of Directors
Charles Ryan, J.D., Ph.D. – President
Guenter R. Janhofer, M.D., Ph.D. – Chief Medical Officer
Brendan Hannah, M.B.A. – Chief Business Officer and Principal Financial Officer
Giovanni Mambrini, MSc – Chief Technology Officer
Thomas Sabia, M.B.A. – Chief Commercial Officer
Pamela Williamson, RAC, FRAPS, M.B.A. – Head of Regulatory Affairs
EryDel’s former Chief Executive Officer, Luca Benatti, Ph.D., also joins Quince’s Board of Directors.

The acquisition of EryDel was completed with no upfront cash payment, using a stock-for-stock exchange and potential downstream milestone cash payments. EryDel stockholders now own 15.2% of Quince’s outstanding shares and may be issued up to an additional 725,036 shares of the company’s common stock (equal to 16.6% of Quince’s currently outstanding shares – inclusive of the shares issued) upon the first anniversary of the transaction closing. EryDel stockholders also will be entitled to up to $485 million in potential total downstream cash payments, including up to $5 million in development milestones, $25 million at NDA acceptance, $60 million in approval milestones, and $395 million on market and sales milestones, with no royalties paid to EryDel stockholders. The transaction includes the assumption of EryDel’s $13 million (€10 million in principal) European Investment Bank (EIB) loan with scheduled payments beginning in the second half of 2026.

On October 23, 2023 PDS Biotechnology Corporation (Nasdaq: PDSB) (PDS Biotech or the Company), a clinical-stage immunotherapy company developing a growing pipeline of targeted cancer immunotherapies and infectious disease vaccines based on the Company’s proprietary T cell activating platforms, reported immune response data from a preliminary analysis of a subset of patients in VERSATILE-002, the Phase 2 clinical trial evaluating the safety and efficacy of PDS0101 in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with human papillomavirus (HPV)16-positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) (Press release, PDS Biotechnology, OCT 23, 2023, View Source [SID1234636258]). The data presented during the European Society for Medical Oncology Congress 2023 (ESMO Congress 2023) provided preliminary insight to the pre-existing immune responses in advanced HPV-positive HNSCC patients and potential changes to the immune profile after treatment.

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"Generation of multifunctional, anti-tumor T cells with the relevant cytokine and chemokine profiles are necessary for effective long-term control of tumor growth and clinical outcomes. This initial study focused on understanding the immunological profile of advanced head and cancer patients in the blood," said Kevin Harrington, PhD, Professor of Biological Cancer Therapies, The Royal Marsden. "This preliminary study suggests that PDS0101 may promote a TH1 predominant cytokine profile as well as induction of important T cell activating chemokines. Such studies could be helpful in providing further insight into how PDS0101 in combination with KEYTRUDA alters T cell cytokine and chemokine profiles to promote improved clinical outcomes."

The data presented at ESMO (Free ESMO Whitepaper) 2023 included 18 patients with a median age of 63 years (range 46-83) and all had confirmed HPV16-positive tumors. The immunological profiles were assessed at three timepoints: pre-treatment,12 (cycle 5), and 36 weeks (cycle 13) following four and five cycles of combination therapy, respectively.

Highlights of the analysis include:

•
Combination of PDS0101 and KEYTRUDA appears to lead to changes towards a TH1 predominant cytokine profile reported to be associated with improved killer T cell activity

•
Combination of PDS0101 and KEYTRUDA resulted in increased polyfunctionality reflected in T cells expressing 5 or more cytokines. Increased polyfunctionality is typically associated with enhanced killing function and anti-tumor activity

"This analysis provides preliminary insights into how PDS0101 in combination with KEYTRUDA may be impacting specific cytokines and chemokines in CD8 and CD4 T cell populations," said Lauren V. Wood, MD, Chief Medical Officer of PDS Biotech. "The investigational combination appears to be promoting a predominant TH1 immunologic profile that is associated with decreases in CD8 T cells in peripheral blood. We are encouraged that these observations align with other Phase 2 studies reporting PDS0101-induced polyfunctional CD8 T cells traffic to tumors and we look forward to continued investigation in our VERSATILE-003 Phase 3 study."

1 Klopp A, et al. 2022. IMMUNOCERV, an ongoing Phase II trial combining PDS0101, an HPV-specific T cell immunotherapy, with chemotherapy and radiation for treatment of locally advanced cervical cancers. Presented at: Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper); November 8-12, 2022. Boston, MA. Abstract: 674.

About PDS0101
PDS0101, PDS Biotech’s lead candidate, is a novel investigational human papillomavirus (HPV)-targeted immunotherapy that stimulates a potent targeted T cell attack against HPV-positive cancers. PDS0101 is given by subcutaneous injection alone or in combination with other immunotherapies and cancer treatments. In a Phase 1 study of PDS0101 in monotherapy, the treatment demonstrated the ability to generate multifunctional HPV16-targeted CD8 and CD4 T cells with minimal toxicity. Interim data suggests PDS0101 generates clinically active immune responses and the combination of PDS0101with other treatments can demonstrate significant disease control by reducing or shrinking tumors, delaying disease progression, and/or prolonging survival. The combination of PDS0101 with other treatments does not appear to compound the toxicity of other agents.

About VERSATILE-002
VERSATILE-002 is a single-arm Phase 2 trial evaluating the safety and efficacy of PDS0101, an HPV16-targeted investigational T cell-activating immunotherapy that leverages PDS Biotech’s proprietary Versamune technology, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab). The combination is being evaluated in immune checkpoint inhibitor (ICI)-naïve and ICI-refractory patients with recurrent/metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC) and was granted Fast Track designation by the Food and Drug Administration in June 2022.

On October 23, 2023 Oncolytics Biotech Inc. (NASDAQ: ONCY, Oncolytics) (TSX: ONC), a clinical-stage immunotherapeutics company focused on oncology, reported the poster presentation of positive, updated results from the Phase 1/2 GOBLET study evaluating pelareorep-based combination therapy in patients with pancreatic ductal adenocarcinoma (PDAC) at the European Society for Medical Oncology meeting (ESMO 2023), taking place in Madrid, Spain (Press release, Oncolytics Biotech, OCT 23, 2023, View Source [SID1234636257]).

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"We are very pleased to share such positive and consistent data on pelareorep from the PDAC arm of the GOBLET study, including an impressive overall response rate, 7.2 months of median progression-free survival, interim median overall survival of 10.6 months, and expansion of both pre-existing and new T-cell clones. These data build upon results from previous studies showing the clinical benefit of pelareorep combination therapy in PDAC and support the decision to move to a licensure-enabling study in pancreatic cancer," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics. "Everything we do at Oncolytics is focused on advancing the development of our immunotherapy candidate, pelareorep, with a goal of providing improved care and longer survival for patients with pancreatic cancer and other tumor types. The data we are presenting at ESMO (Free ESMO Whitepaper) provide a solid foundation as we advance our pancreatic cancer program through the Precision PromiseSM Phase 3 trial in this indication."

Summary of Data and Findings from the PDAC Arm of the Phase 1/2 GOBLET Study:

Tumor Responses: Consistent with the abstract, data from the study outlined patient responses, including:
•Objective Response Rate (ORR) of 62% (54% confirmed by two or more scans)
•A Disease Control Rate (DCR) of 85%

Survival data: Evaluated based on 4 parameters including:
•Median duration of response was 5.7 months
•Median progression-free survival (PFS) was 7.2 months
•Interim 12-month survival rate was 46%
•Interim median overall survival (OS) was 10.6 months

T-Cell Populations: Analysis of changes of T-cell clones and tumor-infiltrating lymphocytes (TILs) showed:
•Mean baseline TIL cell levels of 22%
•Expansion of pre-existing and new T cell clones, including the expansion of TIL-specific clones
•A correlation between in the expansion in the blood of TIL-specific clones and tumor response

Safety: The treatment combination has been well tolerated with no safety concerns
•Most common grade 3 and 4 treatment-related adverse events were related to red and white blood cell counts (anemia, neutropenia and decreased neutrophil counts)

"The data from this study show a correlation between the expansion of TIL-specific clones and tumor response, which provides compelling support for the use of pelareorep-based therapies in immunologically "cold" tumors. In particular, these data, along with the impressive clinical results, support the ability of pelareorep-checkpoint inhibitor combination therapies to meaningfully improve treatment responses in diseases like pancreatic cancer that have resisted immune-based therapeutic approaches," said Thomas Heineman, M.D., Ph.D., Chief Medical Officer at Oncolytics. "Given the urgent need for better treatment options for patients with pancreatic cancer, we are especially gratified to observe that results from the combination regimen we are evaluating surpassed published historical results1-4. We look forward to beginning the Precision PromiseSM Pivotal Phase 3 platform trial as soon as
possible, and we wish to express our sincere gratitude to all the patients, caregivers, and study site personnel associated with the GOBLET trial."

GOBLET Study PDAC Patient Overview:
Patients in the PDAC cohort, presented at ESMO (Free ESMO Whitepaper) 2023, are undergoing first-line treatment with a combination of pelareorep, atezolizumab, gemcitabine and nab-paclitaxel. The 13 evaluable patients enrolled in the first stage of the study have been evaluated based on a September 18, 2023 data cut-off date. The enrolled patient population included 93% of patients with metastatic disease (69% with liver metastases) and baseline ECOG scores of 0 (31%) and 1 (69%), with an average age of 61.2 years.

References
1. Von Hoff D et al. N Engl J Med 2013; 369:1691-1703 DOI: 10.1056/NEJMoa1304369
2. O’Reilly et al. Eur J Cancer. 2020 June; 132: 112–121. DOI:10.1016/j.ejca.2020.03.005
3. Karasic et al. JAMA Oncol. 2019 Jul 1; 5(7):993-998. DOI: 10.1001/jamaoncol.2019.0684
4. Tempero et al. Ann Oncol. 2021 May; 32(5):600-608. DOI: 10.1016/j.annonc.2021.01.070

Poster Information
Poster Title Pelareorep (pela) + atezolizumab (atezo) and chemotherapy in first-line (1L) advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) patients – Results from the GOBLET study
Final Publication Number (FPN) 1623P
Poster Date October 23, 2023

About GOBLET
The GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with the oncolytic reovirus peLarEorep and anTi-PD-L1) study is a phase 1/2 multiple indication study in advanced or metastatic gastrointestinal tumors. The study is being conducted at 12 centers in Germany and is being managed by AIO-Studien-gGmbH. The co-primary endpoints of the study are objective response rate (ORR) assessed at week 16 and safety. Key secondary and exploratory endpoints include additional efficacy assessments and evaluation of potential biomarkers (T cell clonality and CEACAM6). The study employs a Simon two-stage design with Stage 1 comprising four treatment groups expected to enroll a total of approximately 55 patients:

1.Pelareorep in combination with atezolizumab, gemcitabine, and nab-paclitaxel in 1st line advanced/metastatic pancreatic cancer patients (n=12);

2.Pelareorep in combination with atezolizumab in 1st line MSI (microsatellite instability)-high metastatic colorectal cancer patients (n=19);

3.Pelareorep in combination with atezolizumab and TAS-102 in 3rd line metastatic colorectal cancer patients (n=14); and

4.Pelareorep in combination with atezolizumab in 2nd line advanced and unresectable anal cancer patients (n=10).

Any cohort showing an ORR above a pre-specified threshold in Stage 1 may be advanced to Stage 2 and enroll additional patients.

About AIO
AIO-Studien-gGmbH (AIO) emerged from the study center of the internal oncology working group within the German Cancer Society (DKG). AIO operates with a non-profit purpose of promoting science and research with a focus on medical oncology. Since its foundation, AIO has become a successful sponsor and study management company and has established itself both nationally and internationally.

On October 23, 2023 Olema Pharmaceuticals, Inc. ("Olema", "Olema Oncology", or the "Company", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted therapies for women’s cancers, reported results from a Phase 2 clinical study of palazestrant (OP-1250), the Company’s complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD), for the treatment of metastatic ER+/HER2- breast cancer (Press release, Olema Oncology, OCT 23, 2023, View Source [SID1234636256]). These results were presented in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 in Madrid, Spain, on October 22, 2023.

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The presentation, titled "Results from the phase 1/2 study of OP-1250, an oral complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD) in patients (pts) with advanced or metastatic ER-positive, HER2-negative breast cancer", highlighted that:

·

Across 86 heavily pretreated patients, where 42% of patients were 4th line or later at study entry, 120 mg once-daily, monotherapy palazestrant was well tolerated and achieved a median progression-free survival (PFS) of 4.6 months and clinical benefit rate (CBR) of 40%, and a median PFS of 5.6 months and CBR of 52% in patients with ESR1 mutations at baseline.

·

In a subset analysis of 49 second- or third-line patients with or without prior chemotherapy (the EMERALD trial eligibility criteria), the median PFS was 7.2 months and CBR was 48% across all patients, and the median PFS was 7.3 months and CBR was 59% ESR1-mutant patients.

"These Phase 2 monotherapy study results demonstrate that palazestrant (OP-1250) has the potential to become a best-in-class endocrine therapy and improve upon current standard of care treatments for women living with metastatic breast cancer. In addition to being well-tolerated, palazestrant has demonstrated compelling progression-free survival as monotherapy in a heavily pretreated patient population," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "Going forward, we are in the process of initiating OPERA-01, our first pivotal Phase 3 clinical trial testing palazestrant as monotherapy in second- and third-line metastatic breast cancer."

Phase 2 Clinical Study Results

Enrollment

As of the data cut-off of July 7, 2023, 86 patients with recurrent, locally advanced or metastatic ER+/HER2- breast cancer were treated at the Recommended Phase 2 Dose (RP2D) of 120 mg. The group was heavily pretreated with 42% of patients being fourth-line or later at study entry, 65% of patients having received two or more prior lines of endocrine therapy for metastatic disease, and 31% having received prior chemotherapy. Almost all patients (97%) received prior treatment with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, and 66% received prior treatment with fulvestrant. Of 75 patients whose circulating tumor DNA (ctDNA) was assessed, 48% had activating mutations in ESR1 at baseline.

Pharmacokinetics

Palazestrant demonstrated favorable pharmacokinetics characterized by high oral bioavailability, dose proportional exposure and a long half-life of eight days, with steady-state plasma levels showing minimal peak-to-trough variability, enabling consistent inhibition of the ER for the full dosing interval.

Safety and Tolerability

Treatment with palazestrant at the RP2D of 120 mg was well tolerated with no dose-limiting toxicities, and the maximum tolerated dose (MTD) was not reached. The majority of treatment-emergent adverse events (TEAEs) were Grade 1 or 2. Of the 86 patients treated, events of Grade 4 neutropenia were observed in six patients, occurring approximately 4–6 weeks into therapy. Of these patients, three had a dose interruption with recovery and subsequent dose reduction (two continued at 90 mg and one continued at 60 mg) without any recurrence, and three had dose discontinuation followed by recovery. All six patients had prior exposure to CDK4/6 inhibitors.

Efficacy

Across all 86 patients, the median PFS was 4.6 months and the CBR was 40% with a 6-month PFS rate of 38%. In patients with an ESR1 mutation, the median PFS was 5.6 months and the CBR was 52% with a 6-month PFS rate of 46%. In ESR1 wild-type patients, the median PFS was 3.5 months and the CBR was 32% with a 6-month PFS rate of 35%.

In a subset analysis of 49 patients that received palazestrant as a second- or third-line therapy with or without prior chemotherapy (the EMERALD trial eligibility criteria), the median PFS was 7.2 months and the CBR was 48% across all patients with a 6-month PFS rate of 54%. In patients with an ESR1 mutation, the median PFS was 7.3 months and CBR was 59% with a 6-month PFS rate of 62%. In ESR1 wild-type patients the median PFS was 5.5 months and the CBR was 38% with a 6-month PFS rate of 44%.

Anti-tumor activity was observed in this heavily pre-treated population, with 40% of patients demonstrating reduction in target lesions and evidence of activity in both ESR1 wild-type and ESR1-mutant patients. Given the advanced and heavily pretreated nature of the patients, many of these patients are expected to be resistant to monotherapy endocrine treatment.

Company Investor Webcast and Conference Call

Olema will host a webcast and conference call for analysts and investors to review data presented at ESMO (Free ESMO Whitepaper) 2023 on Monday, October 23, 2023, at 8:00 a.m. ET (5:00 a.m. PT). Dr. Nancy Lin, Associate Chief of the Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, at the Dana-Farber Cancer Institute in Boston, MA, will join Olema management for the call. Please register for the webcast by visiting the Investors & Media section of Olema’s website at olema.com.

A copy of the oral presentation is available on Olema’s website under the Science section of the Olema website.

On October 23, 2023 Novartis reported data from the Phase III PSMAfore trial at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (Press release, Novartis, OCT 23, 2023, View Source [SID1234636255]). Data presented at the Presidential Symposium showed that Pluvicto (lutetium (177Lu) vipivotide tetraxetan) met its primary endpoint with a clinically meaningful and statistically significant benefit in radiographic progression-free survival (rPFS) in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) after treatment with androgen receptor pathway inhibitor (ARPI) therapy, compared to a change in ARPI1.

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Efficacy endpoint Pluvicto vs. change in ARPI
Radiographic progression-free survival *a HR 0.41 (95% CI: 0.29, 0.56; p<0.0001)
Median rPFS* 12.0 vs. 5.6 months
≥50% decline in prostate-specific antigen levels 57.6% vs. 20.4%
Time to symptomatic skeletal event (SSE)a HR 0.35 (95% CI: 0.22, 0.57)
Objective response rate (ORR)b 50.7% vs. 14.9%
Duration of response (DOR)b 13.6 vs. 10.1 months
FACT-P scorea HR 0.59 (95% CI: 0.47, 0.72)
Brief Pain Inventory-Short Form (BPI-SF)a HR 0.69 (95% CI: 0.56, 0.85)
Prespecified crossover-adjusted overall survivala HR 0.80 (95% CI: 0.48, 1.33)
Unadjusted OSa (84% crossover) HR 1.16 (95% CI: 0.83, 1.64)
a Hazard Ratio (95% Confidence Interval). Functional Assessment of Cancer Therapy-Prostate
b In patients with measurable disease at baseline in soft tissue per RECIST v1.1.

"The rPFS data are impressive and the treatment effect is comparable with what was observed in the VISION trial," said Dr. Oliver Sartor, PSMAfore Co-Principal Investigator, Chairman of the Trial Steering Committee and adjunct professor in the Department of Urology at Tulane University School of Medicine, New Orleans, LA, one of the many sites where the trial was conducted. "We look forward to a future where Pluvicto may be a viable therapy for patients in need of alternative, earlier options."

"These promising results from PSMAfore could change the treatment paradigm for advanced prostate cancer by allowing patients to potentially avoid or delay taxane-based chemotherapy, which carries a heavy burden of side effects," said Jeff Legos, Executive Vice President, Global Head of Oncology Development at Novartis. "While data collection for overall survival continues, the consistency of the benefit observed on other clinically meaningful efficacy endpoints, together with improved quality of life and favorable safety profile, show the potential of Pluvicto for taxane-naïve patients with mCRPC."

The trial met its primary endpoint of rPFS2 with a 59% reduction in the risk of radiographic disease progression in patients with Pluvicto versus a change of ARPI1. Using a data cut off with a median of 8.6 months longer study follow-up, an updated rPFS analysis (HR 0.43; 95% CI: 0.33, 0.54) demonstrated a consistent clinical benefit in patients with Pluvicto versus a change in ARPI, more than doubling time to radiographic disease progression (12.0 months vs. 5.6 median months)1.

Patients on Pluvicto also showed improved quality of life, maintaining their FACT-P total score for 3 months longer than a change in ARPI (7.5 vs. 4.3 months), with a delay in worsening pain (BPI-SF) of 5.0 versus 3.7 months1. Other clinically meaningful efficacy endpoints also favored Pluvicto, with a PSA decline of at least 50% being >2.5X more frequent with Pluvicto than with a change in ARPI1.

At the second interim OS analysis with 45% of events, the pre-specified crossover-adjusted OS analysis demonstrated a hazard ratio of 0.80 (95% CI: 0.48, 1.33)1. The unadjusted intent-to-treat OS analysis was confounded as 84% of patients who discontinued ARPI due to radiographic progression crossed over to receive Pluvicto1. The trial will continue to assess OS, with the next interim OS analysis expected in 2024.

The trial demonstrated a favorable safety profile with 6 cycles of Pluvicto1:

Adverse events (AEs) Pluvicto vs. change in ARPIa
Grade 3–4 33.9% vs. 43.1%
Serious 20.3% vs. 28.0%
Leading to dose-adjustment 3.5% vs. 15.1%
Leading to discontinuation 5.7% vs. 5.2%
a In patients who experienced ≥1 adverse event.

The most frequently reported all-grade AEs for Pluvicto were primarily Grade 1–2 and included dry mouth (57.3%), asthenia (31.7%), nausea (31.3%), anemia (24.2%) and fatigue (22.9%)1.
Currently, patients diagnosed with metastatic prostate cancer have a 5-year survival rate of approximately 30%3 and there remains an urgent need for treatment options for patients who have disease progression despite the current standard of care4-7.

*Pluvicto met its primary endpoint of rPFS at the primary analysis based on centrally confirmed rPFS events with an October 2022 data cut off1. The updated exploratory rPFS analysis was based on the latest data cut off of June 2023 and only nominally significant1.

About the PSMAfore Study
PSMAfore (NCT04689828) is a Phase III, open-label, multi-center, 1:1 randomized study comparing the efficacy and safety of Pluvicto to a change in ARPI (abiraterone or enzalutamide) in patients with PSMA-positive mCRPC who have not been exposed to a taxane-containing regimen8. Patients enrolled must have progressed only once after receiving a second-generation ARPI (abiraterone, enzalutamide, darolutamide or apalutamide)8.

Patients randomized to the change in the ARPI arm were allowed to crossover to receive Pluvicto upon confirmation of radiographic progression by blinded independent central review (BICR). There were 469 participants enrolled in the study8.

The primary endpoint is rPFS, defined as the time from randomization to radiographic progression by PCWG3-modified RECIST v1.1 (as assessed by BICR) or death8. The key secondary endpoint of OS is defined as the time from date of randomization until the date of death due to any cause8. The pre-specified crossover-adjusted OS analysis was performed using the rank-preserving structural failure time (RPSFT) model to adjust for crossover8.

About Pluvicto (lutetium (177Lu) vipivotide tetraxetan)
Pluvicto is an intravenous radioligand therapy (RLT) combining a targeting compound (a ligand) with a therapeutic radionuclide (a radioactive particle, in this case lutetium-177)9,10. After administration into the bloodstream, Pluvicto binds to target cells, including prostate cancer cells that express PSMA, a transmembrane protein9,10. Once bound, energy emissions from the radioisotope damage the target cells and nearby cells, disrupting their ability to replicate and/or triggering cell death10.

Pluvicto is approved in the U.S., the E.U. and other countries to treat adults with a type of advanced cancer called PSMA-positive mCRPC and who have already been treated with other anticancer treatments (ARPI and taxane-based chemotherapy)11-15. These regulatory decisions are supported by the results from the pivotal Phase III VISION trial, where Pluvicto met both primary endpoints of OS and rPFS, reducing the risk of death by 38% and the risk of radiographic progression or death by 60% compared to standard of care9.

As part of our goal to move into earlier stages of disease, we have two additional Phase III studies to evaluate Pluvicto in earlier lines of treatment for PSMA-positive prostate cancer: PSMAddition (NCT04720157) is ongoing in the metastatic hormone-sensitive setting and PSMA-DC (NCT05939414) in the oligometastatic setting is in preparation. More information on these studies may be found at www.clinicaltrials.gov