On December 10, 2021 Carrick Therapeutics, an oncology-focused biopharmaceutical company discovering and developing highly differentiated therapies, reported at the 2021 San Antonio Breast Cancer Symposium (SABCS), presented encouraging clinical data on samuraciclib (CT7001), an oral and first-in-class inhibitor of CDK7, that support its continued development in breast cancer (Press release, Carrick Therapeutics, DEC 10, 2021, View Source [SID1234596751]).

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Carrick presented updated data from a Phase 1b/2 clinical trial for samuraciclib in combination with fulvestrant in women with hormone receptor positive (HR+), HER2- advanced breast cancer (BC) previously treated with a CDK4/6 inhibitor (abstract: GS3-10) that reinforces encouraging clinical activity and tolerability and supports further development of the combination.

"The data we announced at SABCS both demonstrated clinical activity and tolerability, which has reinforced our conviction that samuraciclib has potential to be a first and best-in-class treatment," said Tim Pearson, Chief Executive Officer of Carrick Therapeutics. "Our pre-clinical studies have established that CDK7 inhibition activates the p53 pathway in TP53 wild-type, HR+ breast cancer cells. More importantly, p53 pathway activation by samuraciclib in combination with CDK7 inhibition has been effective in controlling cancer growth in our HR+ clinical study. Samuraciclib, provides meaningful benefit most notably in those women that are TP53 wildtype, which accounts for nearly 70% of patients in this setting. Samuraciclib in combination with fulvestrant in the post CDK4/6 setting has demonstrated a median mPFS of 32 weeks. This is a meaningful prolongation of PFS considering the limited benefit these patients have with endocrine monotherapy therapy, which is limited to only ~8 weeks mPFS with fulvestrant alone in previously reported studies. Having now validated the biology for SERD combination, we continue to explore additional options, including our collaboration with Roche’s giredestrant, a next-generation oral SERD. We believe there is potential for synergy in combining samuraciclib with oral SERDs to significantly enhance the benefits already demonstrated with fulvestrant. We are excited with the progress we’ve made, and we look forward to additional data readouts from our ongoing programs."

The study recruited patients with advanced HR+, HER2- BC, 31 patients were enrolled with difficult-to-treat disease. All patients enrolled had progressed following treatment with a CDK4/6 inhibitor and 23% had received chemotherapy for advanced disease. All patients had advanced disease with 81% having visceral involvement, including 45% with liver metastasis and only 6% with bone only disease.

Of the 31 patients enrolled in this ongoing study, 25 patients were evaluable for response at the time of data cut-off:

Overall the clinical benefit rate (CBR) of patients who received treatment for at least 24 weeks was 36% (9 patients).
However clinical benefit was particularly evident in patients with no deleterious mutation in the TP53 gene and patients without liver metastases.
Median progression-free survival (mPFS) TP53 wild-type (n=19) was 32 weeks vs 7.9 weeks for TP53 mutant (n=6).
mPFS with no liver metastases (n=17) was not reached (?48 weeks) vs 11.9 weeks for patients with liver metastases (n=14).
18 (72%) had tumour shrinkage including 3 partial responses (1 confirmed, 2 unconfirmed)
The combination treatment was generally well tolerated. Adverse events were predominantly low-grade gastrointestinal (GI) events such as nausea, vomiting and diarrhea with the majority of patients staying on treatment until disease progression.
This additional data supports the further development of samuraciclib in HR+ advanced breast cancer.
Carrick also presented data for the use of samuraciclib in patients with advanced triple negative breast cancer (TNBC) (abstract: P1-18-10) which demonstrated evidence of antitumor activity that support its further development as a platform for combination approaches in TNBC. In this study, 23 patients with advanced TNBC were recruited and dosed with samuraciclib 360mg OD.

Samuraciclib demonstrated evidence of long-term benefit in patients who had received one to three lines of prior chemotherapy:
One patient had a partial response as defined by RECIST, and stable disease was achieved in 11 patients.
Five patients have been on treatment for at least 24 weeks of whom 3 have exceeded 1 year.
Treatment was generally well tolerated with all patients staying on treatment until disease progression. Adverse events were predominantly GI events of low-grade.
Samuraciclib has shown evidence of target engagement on several biomarkers that supports its mechanism of action. In addition, plasma thymidine kinase activity, a measure of cell cycle progression, was inhibited with samuraciclib administration.
About Samuraciclib (CT7001)
Samuraciclib is the most advanced oral CDK7 inhibitor in clinical development. Inhibiting CDK7 is a promising therapeutic strategy in cancer as CDK7 regulates the transcription of cancer-causing genes, promotes uncontrolled cell cycle progression and resistance to anti-hormone therapy. Samuraciclib has demonstrated a favorable safety profile and encouraging efficacy in early clinical studies. In addition to the above studies, it is currently being evaluated in prostate cancer with further potential in pancreatic, ovarian and colorectal cancers. Samuraciclib has been granted Fast Track designations from the U.S. Food and Drug Administration (FDA) for use in combination with fulvestrant for the treatment of CDK4/6i resistant HR+, HER2- advanced breast cancer and in combination with chemotherapy for the treatment of locally advanced or metastatic TNBC.

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 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 Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) reported an update on Phase 1 dose escalation data of ARV-471, a novel PROTAC estrogen receptor (ER) degrader, which is being co-developed for the treatment of patients with locally advanced or metastatic ER-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (ER+/HER2-) (Press release, Arvinas, DEC 10, 2021, View Source [SID1234596747]). These data were presented as a virtual spotlight poster session at the 2021 San Antonio Breast Cancer Symposium (SABCS) and showed:

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ARV-471 demonstrated antitumor activity in CDK4/6 inhibitor-pretreated patients with a clinical benefit rate (CBR) of 40% in 47 evaluable patients. This heavily pretreated patient group had a median of four prior therapies.
Three patients exhibited confirmed partial responses (PR) among the 38 patients with response evaluation criteria in solid tumors (RECIST) measurable lesions and at least one on-treatment tumor assessment.
ARV-471 continues to demonstrate a favorable tolerability profile. Robust ER degradation was observed at all dose levels, reaching 89% reduction of ER.
Erika P. Hamilton, MD, Director of the Breast Cancer and Gynecologic Cancer Research Program and Principal Investigator, Sarah Cannon Research Institute, provided an overview of these data.

"These results continue to suggest that ARV-471 has the potential to become a first-in-category treatment, and a new standard of care, for ER+/HER2- breast cancer patients," said John Houston, Ph.D., Chief Executive Officer at Arvinas. "The profile we see emerging for this drug candidate continues to validate our PROTAC protein degrader platform, with ARV-471 showing clear signals of clinical benefit in a heavily pretreated patient population, including tumor shrinkage and good tolerability."

These data support and further validate the evaluation of ARV-471 as a potential treatment for metastatic breast cancer that is ongoing in a Phase 1b combination study with IBRANCE (palbociclib) and a Phase 2 monotherapy dose expansion study.

"We are excited by these results and believe ARV-471 is a promising ER-targeting investigational medicine," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "It is encouraging to see ARV-471 continuing to show durable efficacy and tolerability in heavily pre-treated patients with ER+ breast cancer who have limited treatment choices."

ARV-471 Clinical Update

Enrollment

As of the data cut-off date of September 30, 2021, 60 adult patients with locally advanced or metastatic ER+/HER2- breast cancer were treated in the Phase 1 dose escalation portion of the study with total daily ARV-471 doses ranging from 30 mg to 700 mg. This patient group is heavily pretreated, with a median of four prior therapies. All patients were previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitors; 80% of patients received prior fulvestrant; and 78% received prior chemotherapy.

Efficacy

Of 47 patients who were evaluable for clinical benefit (confirmed complete response, PR, or stable disease ≥ 24 weeks) the CBR was 40%. As of the data cutoff date, 14 patients were continuing to receive study treatment, including two patients who had been on treatment for over 18 months. Three confirmed PRs were observed among the 38 patients with baseline RECIST measurable disease and at least one on-treatment tumor assessment.

Safety

Patients were treated in the monotherapy escalation at total daily doses of 30 mg (n=3), 60 mg (n=3), 120 mg (n=7), 180/200 mg (n=11), 360 mg (n=15), 500 mg (n=17), and 700 mg (n= 4). All patients in the 700 mg cohort received ARV-471 twice-daily, a subset of patients who received 500 mg as a total daily dose received ARV-471 twice-daily, and other all doses were administered once-daily. A maximum tolerated dose was not reached and no dose limiting toxicities or Grade ≥4 treatment-related adverse events (TRAEs) were observed. Of the 60 patients, 37% had Grade 1 TRAEs and 57% had Grade ≤2 TRAEs, and the most common TRAEs were nausea (29%), fatigue (20%), and vomiting (10%). No Grade 1 or 2 TRAEs led to discontinuation or dose reduction of ARV-471. Four patients experienced six Grade 3 TRAEs that were potentially related to ARV-471, including: headache lasting 1-day, single occurrence of asymptomatic increased amylase and lipase, nausea and asymptomatic QTc prolongation, and post-biopsy venous embolism. The patient with the venous embolism was the only Grade 3 patient who discontinued ARV-471 due to a TRAE, and the patient with Grade 3 nausea was the only patient with a dose reduction due to a TRAE (reduced from 500 mg to 400 mg daily).

ER Degradation

In paired biopsies from 14 patients across all doses up to 500 mg daily, robust ER degradation of up to 89% was observed, regardless of ESR1 mutation status. Median and mean ER degradation across dose levels were 67% and 64%, respectively.

Pharmacokinetics

ARV-471 demonstrated a dose-related increase in plasma exposure, with doses from 30 mg to 500 mg daily, resulting in steady-state Cmax and AUC24 that exceeded the exposure associated with tumor regression in preclinical breast cancer models. Mean exposure on day 15 exceeded the nonclinical efficacious range at doses ≥60 mg daily.

Anticipated 2021/2022 Milestones

ARV-471 currently is being evaluated as a treatment for metastatic breast cancer in a Phase 1 dose escalation study, a Phase 1b combination study with IBRANCE (palbociclib), and a Phase 2 monotherapy dose expansion study.
In 2022, we expect to:
Initiate Phase 3 studies across lines of therapy in metastatic breast cancer, as both monotherapy and in combination.
Initiate two additional trials of ARV-471, including a Phase 1b combination trial with everolimus in 2L/3L metastatic breast cancer, potentially as part of a planned umbrella study to explore multiple combination agents, and a Phase 2 neoadjuvant trial in early breast cancer.
Present data from the ongoing Phase 1b combination study with IBRANCE (palbociclib) and from the ongoing Phase 2 monotherapy dose expansion study.
Investor Conference Call Details
Arvinas will host a conference call and webcast at 8:30 AM ET on Friday, December 10, 2021, to discuss these data. Pfizer Oncology executives will also participate in this call. Participants are invited to listen by dialing (844) 467-7654 (domestic) or (602) 563-8497 (international) five minutes prior to the start of the call and providing the passcode 9122219.

Supporting materials for the conference call and webcast will be available on the Arvinas’ website at www.arvinas.com under Events + Presentations. A replay of the webcast will be archived on the Arvinas website following the presentation.

About ARV-471
ARV-471 is an investigational orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.

In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of ARV-471; Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits.

On December 10, 2021 Abbott (NYSE: ABT) reported that its board of directors has increased the company’s quarterly common dividend, marking the company’s 50th consecutive year of dividend growth (Press release, Abbott, DEC 10, 2021, View Source [SID1234596746]).

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Abbott’s quarterly common dividend has been increased to 47 cents per share, a 4.4% increase that follows a 25% increase to the company’s quarterly dividend in 2021. It will be the 392nd consecutive quarterly dividend to be paid by Abbott since 1924. The cash dividend is payable Feb. 15, 2022, to shareholders of record at the close of business on Jan. 14, 2022.

Abbott is a member of the S&P 500 Dividend Aristocrats Index, which tracks companies that have increased dividends annually for at least 25 consecutive years.

"Fifty years of dividend growth reflects the consistently strong performance of our diversified business model," said Robert B. Ford, president and chief executive officer, Abbott. "It exemplifies our longstanding commitment to delivering sustainable growth that fuels innovation as well as shareholder returns."

Abbott’s board also has authorized the repurchase of up to $5 billion of the corporation’s common shares. This new authorization is in addition to the unused portion of the previous program authorized by Abbott’s board in October 2019. The purchases may be made from time to time as market conditions warrant and subject to regulatory considerations.