On December 10, 2021 BeyondSpring Pharmaceuticals (the "Company" or "BeyondSpring") (NASDAQ: BYSI), a global pharmaceutical company focused on the development of cancer therapeutics, reported the presentation of additional analyses from the Phase 3 portion of the PROTECTIVE-2 trial evaluating the combination of plinabulin and pegfilgrastim for the prevention of chemotherapy-induced neutropenia (CIN) in breast cancer patients at the 2021 San Antonio Breast Cancer Symposium (SABCS), held both live and virtually from December 7-10, 2021 (Press release, BeyondSpring Pharmaceuticals, DEC 10, 2021, View Source;utm_medium=rss&utm_campaign=beyondspring-pharmaceuticals-announces-analysis-of-new-data-on-the-plinabulin-pegfilgrastim-combination-in-breast-cancer-at-the-2021-san-antonio-breast-cancer-symposium [SID1234596748]).

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"We’ve been able to demonstrate that adding plinabulin to pegfilgrastim significantly alleviates pegfilgrastim-related bone pain, decreases toxicity and improves health related quality-of-life (HrQoL) through new data analysis from the PROTECTIVE-2 study," said Dr. Douglas Blayney, professor of medicine at Stanford University Medical School and global principal investigator for the CIN studies. "With the superior CIN prevention benefit, the bone pain reduction benefit and quality of life benefit from adding plinabulin to pegfilgrastim, the TAC regimen (docetaxel, doxorubicin and cyclophosphamide) has the potential to become more tolerable in patients with breast cancer."

Dr. Ramon Mohanlal, executive vice president of research and development and chief medical officer at BeyondSpring Pharmaceuticals, added, "We’re pleased to be presenting at SABCS again this year and adding this new important data to our existing portfolio of CIN studies. Our goal has always been to create a better cancer treatment experience for these patients by alleviating some of the issues that can occur with CIN. We look forward to continuing to study how plinabulin can potentially make a difference in this indication."

The posters will be presented by Dr. Blayney during Poster Session 5 on Friday, December 10, 2021, from 8:00 AM to 9:30 AM EST and will be available on the SABCS website.

Poster Title: Mechanistic evidence associated with the benefit of plinabulin significantly reducing bone pain in breast cancer patients (pts) treated with TAC (docetaxel, doxorubicin, cyclophosphamide) and pegfilgrastim (Peg)
Publication Number: P5-18-01
Key Findings:

Patients treated with pegfilgrastim and plinabulin experienced less bone pain than did patients treated with pegfilgrastim only (p=0.03).
Treatment with plinabulin may mitigate the need for compensatory hematopoiesis and intracavitary pressure build-up, resulting in bone pain sensations.
Patients treated with pegfilgrastim and plinabulin had a higher absolute neutrophil count (ANC) at the nadir (the point of their lowest ANC).
Treatment-emergent adverse events of bone pain, cycles 1 to 4 (% of patients): TAC+Peg (30%) vs TAC+Peg+Plin (18%), p=0.03
ANC nadir during cycle 1 (mean ANC nadir (109 cells/L)): TAC+Peg (0.32) vs TAC+Peg+Plin (0.54), p=0.0002.
The depth of ANC nadir was statistically significantly correlated with bone pain scores; TAC+Peg vs TAC+Peg+Plin, p=0.019.
Poster Title: Combination plinabulin+pegfilgrastim (Plin+Peg) had better toxicity management and health related quality-of-life (HrQoL) compared to Peg alone in early-stage breast cancer (BC) patients (pts) treated with taxotere, doxorubicin and cyclophosphamide (TAC)
Publication Number: P5-18-04
Key Findings:

Adding plinabulin to pegfilgrastim decreases toxicity and improves HrQoL among patients with breast cancer receiving TAC. TAC should be reevaluated for patients with early-stage breast cancer in light of the improved outcomes seen with the addition of plinabulin and pegfilgrastim.
The adverse event (AE) profile among patients treated with plinabulin and pegfilgrastim was shifted towards lower grade AEs.
Adding plinabulin to pegfilgrastim prevented a decline in HrQoL scores for mobility, self-care, daily activities, pain and anxiety; significant change in EQ-5D-5L utility values, Cycles 1 to 4 for TAC+Peg vs TAC+Peg+Plin, p=0.024
About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA), which is a potent antigen presenting cell (APC) inducer. It is a novel, intravenous infused, patent-protected asset for CIN prevention and a Phase 3 anti-cancer candidate for non-small cell lung cancer (NSCLC) with recently released positive topline data. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells, and the second is early-onset of action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs). Plinabulin received Breakthrough Therapy designation from both U.S. and China FDA for the CIN prevention indication. As a "pipeline in a drug," plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody-resistant patients.

On December 10, 2021 Novartis reported new Piqray (alpelisib) data indicating benefit across a broad range of patient and disease characteristics as seen in analyses from all three cohorts of BYLieve (Press release, Novartis, DEC 10, 2021, View Source [SID1234596768]). BYLieve is an ongoing Phase II, open-label, 3-cohort non-comparative study evaluating Piqray with endocrine therapy including men and pre- and postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer (mBC) who have progressed on or after prior therapies, including CDK4/6 inhibitor plus endocrine therapy1-5. These data will be presented at the 2021 San Antonio Breast Cancer Symposium (SABCS) from December 7-10.

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"The data from all three cohorts of the BYLieve study have value for the medical community and for the patients we care for with mBC, because these cohorts show a benefit from alpelisib in the post-CDK4/6i setting for patients with HR+/HER2- PIK3CA-mutated cancer," said Dr. Hope S. Rugo, Director, Breast Oncology and Clinical Trials Education, University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center. "Beyond illustrating the efficacy and safety of alpelisib, regardless of the duration of prior CDK4/6i treatment, the data provide meaningful insights into how alpelisib may benefit different subgroups of patients."

Highlights from the BYLieve data presented at SABCS

BYLieve Cohort A (P1-18-03): Updated safety and efficacy data after 18 months of follow-up showed median overall survival improvement of 26.4 months (95% CI: 21.0-30.5) for patients treated with Piqray plus fulvestrant immediately following CDK4/6i plus an AI1. The most common all-grade adverse events (AEs) (n=127) were diarrhea (63.8%), hyperglycemia (59.8%), nausea (46.5%) and rash (31.5%)1.

BYLieve Cohort C (PD13-05): The third and final BYLieve cohort included patients who received chemotherapy or endocrine therapy as immediate prior treatment, who could have received prior CDK4/6i as well2.
The primary endpoint was met with 48.7% (95% CI: 39.3%-58.2%) of patients alive and without disease progression at six months2.
Data confirm clinically relevant activity of Piqray as a targeted therapy for PIK3CA as a driver oncogene2.
No new safety signals were observed, with the most common all-grade AEs (n=126) being hyperglycemia (65.1%), diarrhea (52.4%), nausea (40.5%) and rash (38.9%)2.
BYLieve Cohorts A & B (P1-18-08; P5-13-03; PD15-01): Exploratory biomarker and post-hoc analyses demonstrated efficacy with Piqray plus fulvestrant/letrozole in CDK4/6i-resistant mBC, as seen in patients with early discontinuation of the prior CDK4/6i (Cohort A: ≤6 months median PFS of 12.0 months and >6 months median PFS of 6.2 months; HR=0.51; 95% CI: 0.29-0.89; Cohort B: ≤6 months median PFS of 5.9 months and >6 months median PFS of 5.6 months; HR=0.72; 95% CI: 0.45-1.18), supporting the use of Piqray plus endocrine therapy as an immediate next-line option in these patients3. Grade ≥3 AEs were experienced by 84.6% (n=22) and 66.0% (n=66) of patients in the ≤6 months and >6 months subgroups, respectively, in Cohort A and by 62.5% (n=20) and 72.5% (n=66) of patients in the ≤6 months and >6 months subgroups, respectively, in Cohort B3.
Additionally, the exploratory ctDNA analysis from Cohorts A and B (median PFS of 7.3 months and 5.7 months in Cohorts A and Cohort B, respectively) found that Piqray was effective in the post-CDK4/6i setting regardless of endocrine therapy partner and tumor genomic profile and other mutations associated with CDK4/6i resistance4. Across the three cohorts no new safety signals were observed, even with longer exposure, as seen in Cohort A, confirming no cumulative toxicities with Piqray1-3.

An estimated 361,826 people are diagnosed with mBC worldwide each year, and approximately 40% of those with HR+/HER2- subtype have a PIK3CA mutation, which is associated with a poor prognosis8-9.

Visit View Source for the latest information from Novartis, including our commitment to the Oncology community, and access to our SABCS Virtual Scientific Program data presentations (for registered participants).

About Piqray (alpelisib)
Piqray is a kinase inhibitor developed for use in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after endocrine-based regimen7. Piqray is approved in 64 countries, including the US and European member states12.

Novartis is continuing to reimagine cancer with additional trials of Piqray. EPIK-B5 will be a large Phase III clinical trial of Piqray in combination with fulvestrant to complement the SOLAR-1 study13. Novartis is also studying the potential of Piqray in triple negative breast cancer (TNBC) in the EPIK-B3 Phase III clinical trial, in advanced HER2+ breast cancer in the EPIK-B2 Phase III clinical trial and in ovarian cancer in the EPIK-O Phase III clinical trial14-16.

About Novartis in Advanced Breast Cancer
Novartis tackles breast cancer with superior science, collaboration and a passion for transforming patient care. We’ve taken a bold approach to our research by including patient populations often neglected in clinical trials, identifying new pathways or mutations that may play a role in disease progression and developing therapies that not only maintain, but also improve, quality of life for patients. Our priority over the past 30 years and today is to deliver treatments proven to improve and extend lives for those diagnosed with advanced breast cancer.

Important Safety Information from the PIQRAY EU SmPC
The most common ADRs and the most common grade 3 / 4 ADRs (reported at a frequency >20% and ≥2%, respectively) were plasma glucose increased, creatinine increased, gamma-glutamyltransferase increased, rash, lymphocyte count decreased, nausea, alanine aminotransferase increased, anaemia, fatigue, lipase increased, decreased appetite*, stomatitis, vomiting*, weight decreased, hypocalcaemia, plasma glucose decreased*, activated partial thromboplastin time prolonged*, alopecia**, diarrhoea, hypokalaemia, hypertension, nausea, creatinine increased, and mucosal inflammation (*<2% grade 3/4 ADRs reported, ** no grade 3/4 ADRs reported).

Piqray can cause serious side effects such as severe hypersensitivity, severe cutaneous reactions, hyperglycaemia, pneumonitis, diarrhoea and osteonecrosis of the jaw.

The following should be taken into consideration prior to or during treatment with Piqray:

Piqray should be permanently discontinued in patients with serious hypersensitivity reactions.

Piqray should not be initiated in patients with a history of severe cutaneous reactions, should be interrupted if signs or symptoms of severe cutaneous reactions are present, and permanently discontinued if a severe cutaneous reaction is confirmed.

Fasting glucose and HbA1c levels should be monitored frequently in the first 4 weeks of treatment, and patients should be advised of the signs and symptoms of hyperglycaemia.

In case of new or worsening respiratory symptoms, the patient should be evaluated for pneumonitis.

Patients should be advised to notify their physician if diarrhoea occurs.

Caution should be exercised when Piqray and bisphosphonates or denosumab are used together or sequentially. Piqray should not be initiated in patients with ongoing osteonecrosis of the jaw.

The efficacy and safety of Piqray has not been studied in patients with symptomatic visceral disease.

Animal studies suggest that Piqray may cause fetal harm in pregnant women. Therefore, as a precaution, women of childbearing potential should use effective contraception while receiving Piqray during treatment and at least 1 week after stopping treatment. Women should not breast feed for at least 1 week after the last dose of Piqray. Piqray may affect fertility in males and females.

On December 10, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage oncology company, developing new precision medicine treatment options for cancer patients in indications with the greatest unmet medical need including KRAS-mutated colorectal cancer, pancreatic cancer, and castrate-resistant prostate cancer, reported that updated data from its lead KRAS-mutated metastatic colorectal cancer program will be featured in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI) (Press release, Cardiff Oncology, DEC 10, 2021, View Source [SID1234596750]). ASCO (Free ASCO Whitepaper)-GI is taking place January 20-22, 2022, both virtually and in-person at the Moscone West Building in San Francisco, California.

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Details on the poster and its corresponding abstract can be found below.

Title: A phase 1b/2 trial of the PLK1 inhibitor onvansertib in combination with FOLFIRI-bev in 2L treatment of KRAS-mutated (mKRAS) metastatic colorectal carcinoma (mCRC)
Abstract Number: 100
Abstract Publication Date: January 18, 2022
Abstract Publication Time: 5:00 PM ET
Poster Session Name: Poster Session C: Cancers of the Colon, Rectum, and Anus
Poster Session Date: January 22, 2022
Poster Session Time: 9:30 AM – 10:55 AM ET
Poster Session Location: Level 1, West Hall (and online)

A copy of the poster will be available on the "Scientific Presentations" section of the Cardiff Oncology website at View Source following its presentation at the meeting.

On December 10, 2021 Candel Therapeutics, Inc. (Nasdaq: CADL), a late clinical stage biopharmaceutical company developing novel oncolytic viral immunotherapies, reported a collaboration with Partnership for Accelerating Cancer Therapies (PACT) and the Cancer Immune Monitoring and Analysis Centers – Cancer Immunologic Data Commons (CIMAC-CIDC) to profile the biomarker response to a combination of CAN-2409 + valacyclovir in combination with anti-PD-1 and PD-L1 immune checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC) (Press release, Candel Therapeutics, DEC 10, 2021, View Source [SID1234596770]).

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Analysis of longitudinal biologic samples from a Candel phase 2 clinical trial will be performed by the CIMAC-CIDC research centers and sponsored by PACT. The assays proposed include in depth immunophenotyping of serial lung biopsies and peripheral blood samples obtained during the clinical trial. Candel’s clinical trial in NSCLC is designed to assess the tumor response to CAN-2409 when added to anti-PD-1 or PD-L1 immune checkpoint inhibitor (ICI) treatment after patients have inadequately responded to ICI with or without chemotherapy. The trial comprises three cohorts; 1) patients whose best response to ICI treatment has been stable disease; 2) patients who have initially responded to ICI treatment, but whose disease is now progressing; and 3) patients who have refractory disease, meaning they are progressing rapidly despite ICI treatment. In each of these settings, minimal to no response is expected from further ICI treatment. The collaboration will analyze samples from each of these cohorts with the aim to identify early biological indicators of response and further stratify potential responders to treatment.

"We have shown that local administration of CAN-2409 monotherapy induces significant remodeling of the tumor immune microenvironment coupled with systemic activation of the immune response," said Francesca Barone, MD, PhD, Vice President and Head of Research at Candel. "We are honored by the selection of our clinical trial by the PACT consortium, which provides an important validation of Candel’s approach to embed the highest levels of scientific rigor in our clinical trials. The data generated through this collaboration will broaden our understanding of the biological response to combination therapy of CAN-2409 with ICI, as we endeavor to bring effective new treatment options to patients with cancer."

About PACT

The Partnership for Accelerating Cancer Therapies (PACT) is a five-year public-private research collaboration launched by the National Institutes of Health, the Foundation for the National Institutes of Health (FNIH), and 12 leading pharmaceutical companies as part of the Cancer MoonshotSM Research Initiatives. The PACT initiative is partnered with the Cancer Immune Monitoring Analysis Centers (CIMACs) and the Cancer Immunologic Data Commons (CIDC) Network to develop and validate a set of standardized and harmonized biomarker assays that profile the response to immuno-oncology interventions, including combination therapies, oncolytic viral immunotherapy, and other novel immunotherapy treatments.

For more information about PACT, visit View Source

About CAN-2409

CAN-2409, Candel’s most advanced oncolytic viral immunotherapy candidate, is a replication-deficient adenovirus that delivers the herpes simplex virus thymidine kinase (HSV-tk) gene to cancer cells. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. The intra-tumoral administration results in the release of tumor-specific neoantigens in the microenvironment. At the same time, the adenoviral serotype 5 capsid protein elicits a strong pro-inflammatory signal in the tumor microenvironment. This creates the optimal conditions to induce a specific CD8+ T cell mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity.

Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Monotherapy activity as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors have previously been shown in several preclinical and clinical settings. Furthermore, CAN-2409 presents a favorable tolerability profile; more than 700 patients have been dosed to date, supporting the potential for combination with other therapeutic strategies without inordinate concern of overlapping adverse events. Currently, Candel is evaluating the effects of treatment with CAN-2409 in non-small cell lung cancer, high-grade glioma, pancreatic cancer, and localized, non-metastatic prostate cancer in ongoing clinical trials.

For more information on this clinical study, please visit: View Source

On December 10, 2021 APIM Therapeutics (APIM), a clinical stage biotech company focusing on the development of novel peptide therapeutics targeting PCNA (Proliferating Cell Nuclear Antigen), reported that a Phase II Investigator Initiated Study (IIS) of ATX-101 will begin enrolling patients with sarcoma at Columbia University Irving Medical Center (Press release, APIM Therapeutics, DEC 10, 2021, View Source,c3468947 [SID1234605479]).

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The clinical study (ClinicalTrials.gov Identifier: NCT05116683) will investigate ATX-101, the lead compound of APIM’s development program, as single agent therapy for patients with leiomyosarcoma and liposarcoma who have received at least one prior treatment. An IND has been granted by the FDA and the local IRB approved the study.

Sarcoma is a rare malignant tumor that originates from connective tissue. Lipo- and leiomyosarcoma are the most frequently observed soft tissue sarcomas. About 12,750 new cases of soft tissue sarcoma are diagnosed in the US every year. Late-stage disease has a poor prognosis with a 5-year survival rate below 20%.

"Sarcoma is a disease with a very high medical need, and new treatments are needed to fight this cancer," said Matthew Ingham, MD, assistant professor of medicine in Hematology & Oncology at Columbia and Principal Investigator of the study. "We are interested in exploring the potential of inhibiting PCNA activity in cancer cells as a potential new therapy for sarcoma patients."

Columbia’s Division of Hematology & Oncology, led by Gary Schwartz, MD, professor of oncology at Columbia, is a leader in translational and clinical research on sarcoma. "ATX-101 has shown encouraging pre-clinical data published in peer reviewed journals," said Dr. Schwartz. "We have been able to confirm these data in our lab. Our study will help us determine if this therapeutic approach has clinical benefit for sarcoma patients."

APIM supports the study financially and provides the investigational drug ATX-101. "APIM is happy to support this IIS. Data from our Phase I study indicate a favorable safety profile of ATX-101, including anticancer activity. This sarcoma study is a valuable complement to our own clinical development program investigating ATX-101 in combination with chemotherapy for patients with ovarian cancer," explained Dr. Jens-Peter Marschner, CMO of APIM.

"Our work with distinguished sarcoma specialists at Columbia University Irving Medical Center is an important step for APIM Therapeutics and indicates that our first in class approach is of academic interest," said Dr. Kostas Alevizopoulos, CEO of APIM. "With this IIS and its translational investigations, additional data will be collected that advance our understanding of complex PCNA-dependent activities in cancer and their inhibition by ATX-101."

About ATX-101

ATX-101 is a first-in-class, cell penetrating peptide featuring a novel PCNA-interacting motif (AlkB homolog 2 PCNA Interacting Motif or APIM). In preclinical experiments, it was shown that APIM-containing proteins bind to PCNA and mediate processes of escape mechanisms and survival of cancer cells. ATX-101 competitively inhibits interaction of PCNA with APIM-containing protein complexes resulting in cancer cell death and altered cellular signaling. These properties translate in anticancer effects of ATX-101 as demonstrated in several preclinical models in vitro and in vivo.