On June 2, 2021 Novartis reported updated median overall survival (OS) results for Kisqali (ribociclib) in combination with fulvestrant in postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (Press release, Novartis, JUN 2, 2021, View Source [SID1234583369]). The exploratory analysis of OS after an additional 16.9 months of follow-up of the Phase III MONALEESA-3 trial evaluated Kisqali plus fulvestrant as first- or second-line treatment compared to fulvestrant alone in postmenopausal women with HR+/HER2- metastatic breast cancer1. The analysis found that with extended follow-up of more than four years, Kisqali in combination with fulvestrant continued to demonstrate a clinically relevant OS benefit of more than a year compared with fulvestrant alone1. These updated median OS data (Abstract #1001) will be presented in an oral presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"Successfully demonstrating overall survival improvements in an incurable disease like metastatic breast cancer is a significant achievement, and is what we ultimately strive for in most clinical trials," said Dennis J. Slamon, MD, Director of Clinical/Translational Research, University of California, Los Angeles Jonsson Comprehensive Cancer Center. "When the MONALEESA-7 trial achieved median OS of nearly five years at SABCS 2020, it was the first time we saw a median survival this long with a CDK4/6 inhibitor in the metastatic setting. It is encouraging to see median OS results of nearly 4.5 years in the MONALEESA-3 study, underscoring that ribociclib offers hope for patients to have a longer life while preserving quality of life."

After a median follow-up of 56.3 months, median OS for patients taking Kisqali in combination with fulvestrant was 53.7 months vs. 41.5 months for fulvestrant alone (HR=0.73; 95% CI: 0.59-0.90)1. Additionally, Kisqali plus fulvestrant had prolonged OS in the first-line (median, not reached vs. 51.8 months; HR=0.64; 95% CI: 0.46-0.88) and second-line (median, 39.7 vs. 33.7 months; HR=0.78; 95% CI: 0.59-1.04) treatment subgroups1. This exploratory ad hoc analysis follows the previously reported MONALEESA-3 OS analysis presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2019 and published in the New England Journal of Medicine, which demonstrated statistically significant OS results for Kisqali in combination with fulvestrant with a 28% reduction in the risk of death (HR=0.72; 95% CI: 0.568-0.924; p=0.00455)6,7. Results from the subgroup analyses were consistent with the survival data seen with the intent-to-treat (ITT) population1.

"As overall survival data mature, we’re proud that Kisqali continues to distinguish itself, offering more life for both younger and older women living with metastatic breast cancer," said Susanne Schaffert, Ph.D., President, Novartis Oncology. "These data confirming the sustained efficacy of Kisqali for a broad range of people with HR+/HER2- metastatic breast cancer regardless of line of therapy are unique and inspiring. Our exploration of the benefits of Kisqali continues as we evaluate its potential in the adjuvant setting."

The need for chemotherapy was delayed to 4 years (48.1 months) in patients taking Kisqali in combination with fulvestrant and 28.8 months in the patients taking fulvestrant alone (HR=0.70; 95% CI: 0.57-0.88). Adverse events were consistent with previously reported Phase III trial results1.

"Breast cancer has recently emerged as the most common cancer among females worldwide. The decrease in screenings due to COVID-19 creates a potential threat to improvements in breast cancer survival," said Jean A. Sachs, MSS, MLSP, CEO of Living Beyond Breast Cancer. "What gives me hope is the continued focus on driving science for our community, and to see progress being made in metastatic breast cancer research as we work toward cures."

Visit View Source for the latest information from Novartis, including our commitment to the Oncology community, and access to our ASCO (Free ASCO Whitepaper)21 Virtual Scientific Program data presentations (for registered participants).

About Kisqali (ribociclib)
Kisqali was initially approved by the US Food and Drug Administration (FDA) in March 2017 and by the European Commission (EC) in August 2017, as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor based on findings from the pivotal MONALEESA-2 trial. Kisqali in combination with an aromatase inhibitor was approved for the treatment of pre-, peri- or postmenopausal women as initial endocrine-based therapy, and also indicated for use in combination with fulvestrant as both first- or second-line therapy in postmenopausal women by the FDA in July 2018 and by the EC in December 2018. Regulatory filings are underway with other health authorities worldwide.

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

Important Safety Information from the Kisqali EU SmPC
Kisqali (ribociclib) is a prescription medicine approved in combination with an aromatase inhibitor as initial endocrine-based therapy in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer or fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. It is not known if Kisqali is safe and effective in children or adolescents. Kisqali can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death. Kisqali is not indicated for concomitant use with tamoxifen due to an increased risk of QT prolongation. Patients should tell their health care provider right away if they have a change in their heartbeat (a fast or irregular heartbeat), or if they feel dizzy or faint. Kisqali can cause serious liver problems. Patients should tell their health care provider right away if they get any of the following signs and symptoms of liver problems: yellowing of the skin or the whites of the eyes (jaundice), dark or brown (tea-colored) urine, feeling very tired, loss of appetite, pain on the upper right side of the stomach area (abdomen), and bleeding or bruising more easily than normal. Low white blood cell counts are very common when taking Kisqali and may result in infections that may be severe. Patients should tell their health care provider right away if they have signs and symptoms of low white blood cell counts or infections such as fever and chills. Before taking Kisqali, patients should tell their health care provider if they are pregnant, or plan to become pregnant as Kisqali can harm an unborn baby. Females who are able to become pregnant and who take Kisqali should use highly effective birth control during treatment and for at least 3 weeks after the last dose of Kisqali. Do not breastfeed during treatment with Kisqali and for at least 3 weeks after the last dose of Kisqali. Patients should tell their health care provider about all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements since they may interact with Kisqali. Patients should avoid grapefruit or grapefruit juice while taking Kisqali. The most common side effects (incidence >=20%) include infections, white blood cell count decreases, headache, cough, nausea, tiredness, diarrhea, vomiting, constipation, hair loss and rash. The most common Grade 3/4 side effects (incidence >5%) were infections, low neutrophils, low leukocytes, low red blood cells, abnormal liver function tests, low lymphocytes, low phosphate levels and vomiting. Abnormalities were observed in hematology and clinical chemistry laboratory tests.

Please see full Prescribing Information for Kisqali, available at www.Kisqali.com.

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.

On June 2, 2021 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported initial data from an ongoing Phase 1b study evaluating ORIC-101, a glucocorticoid receptor antagonist, in combination with nab-paclitaxel, in advanced solid tumors. The data will also be presented in two posters at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held June 4 – 8, 2021 (Press release, ORIC Pharmaceuticals, JUN 2, 2021, View Source [SID1234583387]).

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"We are excited to share initial data from our ORIC-101 clinical program in patients with advanced solid tumors. We are pleased that the combination was well tolerated without evidence of drug-drug interaction and has demonstrated both tumor regression and prolonged stable disease in multiple heavily pretreated tumors," said Pratik S. Multani, MD, chief medical officer. "Although early, we are particularly intrigued by the potential benefit seen in patients with late-line relapsed pancreatic cancer previously treated with nab-paclitaxel, as any retreatment benefit in such patients would not be expected. We are continuing to enroll patients in the expansion cohorts and look forward to reporting updated data from the Phase 1b trial in 2022."

"Having been involved with this study from its design stage, I feel we have developed an optimal combination for this heavily pretreated patient population," said Professor Pamela Munster, MD, Director of the University of California San Francisco’s Early Phase Clinical Trials Unit, and trial investigator and senior author of the ASCO (Free ASCO Whitepaper) poster. "I’m impressed by the extended time on treatment we’ve seen in patients with late-line pancreatic cancer; seeing clinical activity in these patients is quite remarkable."

Trial Design and Initial Results from Phase 1b Clinical Trial

The Phase 1b clinical trial of ORIC-101 in combination with nab-paclitaxel is a single arm, multicenter, open-label study conducted in two parts, intended to establish the recommended Phase 2 dose (RP2D), safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity when administered to patients with advanced or metastatic solid tumors.

In the Part I dose escalation portion of the study, five cohorts of patients across multiple solid tumors were enrolled to evaluate ORIC-101 doses ranging from 80 to 240 mg administered orally in both intermittent and continuous once daily dosing regimens, in combination with either 75 or 100 mg/m2 nab-paclitaxel. Following the completion of the dose escalation portion of the study, the RP2D was determined to be 160 mg of ORIC-101 continuous once daily dosing and 75 mg/m2 of nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle, without requirement for prophylactic granulocyte-colony stimulating factor (G-CSF).

For the Part II dose expansion portion of the study, up to 132 patients are expected to be enrolled across four cohorts, including pancreatic ductal adenocarcinoma (PDAC), ovarian cancer, triple negative breast cancer, and other advanced solid tumors. Enrollment continues in the Part II dose expansion cohorts at 12 clinical sites across the United States. Patients in the dose expansion portion of the study are required to have previously progressed on a taxane-based therapy, with retrospective analysis of GR expression and other potentially predictive biomarkers.

Safety Analyses:

As of March 31, 2021, a total of 31 patients were enrolled across Parts I/II of the study, which included 12 patients treated at non-RP2D doses and 19 patients treated at the RP2D of 160 mg of ORIC-101 continuous once daily dosing and 75 mg/m2 of nab-paclitaxel.
Patients treated at the RP2D were heavily pretreated, with a median of four prior therapies, and all had previously received a taxane-based therapy.
As of the database cutoff date of April 21, 2021, the RP2D was well tolerated; treatment-related adverse events were primarily Grade 1 or 2, with only three Grade 3 events, which all resolved with dose interruption.
There were no treatment-related discontinuations and no requirement for prophylactic G-CSF at the RP2D.
Preliminary Antitumor Activity (as of the database cutoff date of April 21, 2021):

The efficacy evaluable population included a total of 23 patients who had an opportunity for at least one on-treatment tumor assessment.
Five partial responses were observed, one confirmed and four unconfirmed, including in heavily pretreated patients with PDAC, endometrial and breast cancers, who previously progressed on or after a taxane-based therapy.
Further evidence of antitumor activity was demonstrated by prolonged disease stabilization across multiple solid tumors, including PDAC, breast, gastric, esophageal, and testicular cancers.
Notably, three of the four efficacy evaluable patients with late-line relapsed PDAC treated at the RP2D demonstrated extended progression free survival ranging from 3.6 months to 5.3+ months in the third-line or later setting, despite having already previously progressed on nab-paclitaxel.
The poster presentations will be on the ORIC website on June 4, 2021.

ORIC-101 is also being evaluated in a Phase 1b trial in combination with Xtandi (enzalutamide) in metastatic prostate cancer, which is also currently enrolling to the dose expansion portion of the study, and initial interim safety, efficacy, and translational data are expected in the second half of 2021.

Webcast and Conference Call

ORIC will host a conference call and webcast, today at 5:00 p.m. ET. To participate in the conference call, please dial (833) 651-0991 (domestic) or (918) 922-6080 (international) and refer to conference ID 4783288. A live webcast and audio archive of the conference call will be available through the investor section of the company’s website at www.oricpharma.com. The webcast will be available for replay for 90 days following the presentation.

About ORIC-101

ORIC-101 is a potent and selective small molecule antagonist of the glucocorticoid receptor, which has been linked to resistance to multiple classes of cancer therapeutics across a variety of solid tumors. Preclinical in vitro and in vivo data suggest ORIC-101 is able to address key resistance mechanisms of multiple classes of cancer treatments, including taxanes and androgen receptor modulators. Based on preclinical and clinical studies, ORIC-101 is expected to have reduced drug-drug interaction liabilities than other glucocorticoid receptor antagonists. Currently, there are no glucocorticoid receptor antagonists approved by the FDA for the treatment of cancer. Following the successful completion of two Phase 1a trials in over 50 healthy volunteers, ORIC initiated two separate Phase 1b trials of ORIC-101 in combination with (1) Abraxane (nab-paclitaxel) in advanced or metastatic solid tumors and (2) Xtandi (enzalutamide) in metastatic prostate cancer.

On June 2, 2021 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, reported the Company’s Vice President of Business Development Dr. Sari Fishman will present at the BIO Digital International Convention and participate in one-on-one meetings with potential licensing and distribution partners on June 10-11 & 14-18, 2021 (Press release, Can-Fite BioPharma, JUN 2, 2021, View Source [SID1234583402]). Over 3,800 delegates from 2,300 companies are registered for BIO One-on-One Partnering.

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Can-Fite currently has out-licensing agreements for its Namodenoson and Piclidenoson drug candidates in several territories and has received approximately $20 million in upfront and milestone payments to date with additional potential milestone payments of up to approximately $130 million, plus double-digit royalties on net sales following regulatory approval.

"We look forward to productive meetings with potential partners in untapped territories for our drug candidates as we approach several milestones before year-end including announcing topline data from our Phase III psoriasis trial and Phase II COVID-19 study, as well as commencing a pivotal Phase III in liver cancer and a Phase IIb in NASH," stated Can-Fite CEO Dr. Pnina Fishman.

On June 2, 2021 Onco360, the nation’s largest independent Oncology Pharmacy, reported that it has been selected by Takeda to be a specialty pharmacy partner for ALUNBRIG (brigatinib), an oral therapy option for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) (Press release, Onco360, JUN 2, 2021, View Source;positive-Metastatic-Non-Small-Cell-Lung-Cancer-NSCLC [SID1234583419]).

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"Onco360 is excited to become a specialty pharmacy provider for ALUNBRIG patients," said Benito Fernandez, Chief Commercial Officer, Onco360. "As a provider of this important treatment option for patients, Onco360 is committed to supporting the highly specialized needs of ALK-positive metastatic NSCLC patients and their physicians across the United States."

According to the National Cancer Institute’s (NCI) Surveillance, Epidemiology, and End Results (SEER) Program, approximately 235,760 patients will be diagnosed with lung cancer in 2021 with a corresponding 131,880 deaths. Approximately 85% of lung cancer cases are represented by NSCLC. When considering all subtypes of lung cancer as well as stages of the disease, lung cancer patients have a poor five-year overall survival (OS) of 21.7%. Unfortunately, 56% of lung cancer patients will have incurable, metastatic disease at the time of initial diagnosis.1 Approximately 4-to-5% of NSCLC patients have genetic mutations which can be classified as ALK-positive.2

ALUNBRIG is manufactured by Takeda, a commercial-stage biotechnology company. The FDA’s approval of ALUNBRIG is based upon the results of multiple clinical trials including the Phase III ALTA 1L (NCT02737501) clinical trial which demonstrated that ALUNBRIG administration resulted in a 51% improvement in progression-free survival (PFS) compared to XALKORI in treatment-naïve patients with ALK-positive metastatic NSCLC patients.3 For full prescribing information, visit ALUNBRIG.com.

On June 2, 2021 Pacylex Pharmaceuticals, an oncology company unlocking a new approach to cancer therapy, and Greenfire Bio, a new Life Science development and investment company, reported the closing of Series A financing for Pacylex (Press release, Pacylex Pharmaceuticals, JUN 2, 2021, View Source [SID1234645063]). These funds will be used to support the initial Phase 1 clinical investigation of PCLX-001, a first-in-class N-myristoyltransferase (NMT) inhibitor, in Diffuse Large B-Cell Lymphoma and solid tumor patients. Pacylex is leading the development of novel therapies targeting the biological process of myristoylation in cancer.

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"We are excited to be a catalyst for this new innovation in oncology" said Ajit Gill, CEO of Greenfire Bio. "Our goal is to build a portfolio of potential breakthroughs in medicine, and we look forward to seeing PCLX-001 move into the clinic."

"The support from Greenfire Bio is essential for our transformation into a clinical stage company", said Michael Weickert, CEO of Pacylex. "Pioneering a new target and first-in-class therapy is extraordinarily important to expand cancer treatment options and improve patient outcomes. We are delighted to find the right investor with an appreciation for this groundbreaking work."

Clinical site preparations are underway for the open label, dose escalation, Phase 1 clinical trial, principally to evaluate the safety of PCLX-001. The study will enroll 20-30 patients and the Company anticipates that enrollment will begin within the next month. A No Objection Letter from Health Canada was received by Pacylex on March 8, 2021, authorizing the planned Phase 1 Trial of PCLX-001 in relapsed/refractory B-cell Non-Hodgkin Lymphoma and advanced solid malignancies. PCLX-001 is believed to be the first NMT inhibitor that will be clinically tested. Three principal investigators will oversee the clinical study at three clinical sites in Canada: Dr. John Kuruvilla at Princess Margaret Cancer Centre in Toronto, Dr. Randeep Sangha at the Cross Cancer Institute in Edmonton and Dr. Laurie Sehn at the British Columbia Cancer Center in Vancouver.

PCLX-001

PCLX-001 is a small molecule, first-in-class NMT inhibitor, originally developed by the University of Dundee Drug Discovery Unit as part of a program to treat African sleeping sickness funded by Wellcome Trust. Pacylex is developing PCLX-001, which has excellent oral bioavailability, to treat leukemia and lymphoma. PCLX-001 selectively kills cancer cells and completely regresses (eliminates) tumors in animal models of acute myeloid leukemia (AML), diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). PCLX-001 has also been shown to inhibit the growth of lung and breast cancer tumors in animal models. In leukemia, lymphoma and breast cancer patients, the level of NMT2 is correlated with survival, suggesting an important biological role in these cancers. In tests using cultured cancer cells in vitro, PCLX-001 is at least ten times as potent as ibrutinib (Imbruvica) and dasatinib (Sprycel), two clinically approved drugs currently used to treat hematologic malignancies.