On December 10, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the phase II coopERA Breast Cancer study met its primary endpoint in the neoadjuvant treatment of early stage ER-positive, HER2-negative breast cancer (Press release, Hoffmann-La Roche, DEC 10, 2021, View Source [SID1234596754]). Breast cancer is the most frequently diagnosed type of cancer, with major societal impact.2 Hormone receptor (HR)-positive breast cancer is the most common subtype, representing ~70% of all diagnoses, or an estimated 1.6 million cases annually across the world.2,3

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"The coopERA Breast Cancer results show the potential positive impact giredestrant could bring for people with early, oestrogen receptor-positive breast cancer, and provide a strong rationale for our ongoing phase III lidERA Breast Cancer study in the adjuvant setting," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "At Roche, we are striving to develop new treatments that might improve or extend the lives of many people with ER-positive breast cancer."

The coopERA Breast Cancer trial is evaluating the efficacy and safety of neoadjuvant treatment with giredestrant (formerly known as GDC-9545), an investigational next generation selective oestrogen receptor degrader (SERD) versus standard of care treatment (anastrozole) in postmenopausal women with oestrogen receptor (ER)-positive, HER2-negative, untreated early breast cancer. The primary endpoint of the study, which measured suppression of the tumour proliferation marker Ki67 was met, following two weeks of treatment with giredestrant versus anastrozole:1

Giredestrant showed a statistically significant mean Ki67 reduction of 75% (95% CI: –80%, –70%) versus 67% for anastrozole (95% CI: –73%, –59%; p=0.0433).
The secondary endpoint of complete cell cycle arrest rate was 19.6% with giredestrant versus 12.8% with anastrozole (95% CI: -4.25, 17.97), which suggests that giredestrant was better at stopping tumour cell proliferation than anastrozole.
Giredestrant was found to be well tolerated and have a safety profile consistent with previous clinical trials.4,5
Final analysis, including overall response rates and combination data with palbociclib are expected next year.
"A significant unmet need remains in early ER-positive breast cancer with currently around half of people having to stop treatment for reasons such as the toll of side effects," said Sara Hurvitz, coopERA Breast Cancer Principal Investigator. "The superior, robust anti-tumour activity of giredestrant after just two weeks of treatment in coopERA Breast Cancer provides early insights into its potential as an effective and tolerable alternative treatment in the early-stage setting."

The coopERA Breast Cancer study is one of several studies to be presented at the San Antonio Breast Cancer Symposium (7-10 December 2021) showing progress in Roche’s comprehensive ER-positive clinical development programme and it provides further evidence of giredestrant’s clinical activity and tolerable safety profile. This includes:

Abstract #1842 – an analysis of the GO39932 study demonstrated encouraging clinical activity of giredestrant as a single agent and in combination with palbociclib, with consistent activity across analysed biomarkers.6
Abstract #1186 – a comprehensive cardiac safety analysis of the GO39932 study found no clinically relevant cardiac effects with 100 mg of giredestrant. A lower, standardised once-daily 30 mg dose has been selected for the giredestrant development programme.7
Abstract #2041 – a ‘trial in progress’ update on the phase III lidERA Breast Cancer study, investigating giredestrant in over 4,000 people with early-stage ER-positive, HER2-negative breast cancer. It is the first study to evaluate an oral SERD in the adjuvant setting.8

About giredestrant
Giredestrant is a potent, next generation investigational selective oestrogen receptor (SERD) with best-in-class potential. It is designed to fully block oestrogen receptor (ER) signalling with robust receptor occupancy and demonstrates an exceptional preclinical profile. Oestrogen encourages ER-positive breast cancer cells to grow by attaching to the ER. Giredestrant works by blocking this receptor to prevent the action of oestrogen, and in the process causes the receptor to be degraded. This investigational medicine has also shown efficacy regardless of ESR1 mutation status (mutations in the ESR1 gene are important mechanisms of resistance to hormone therapy).9,10,11,12,13

Given orally, giredestrant delivers an encouraging clinical efficacy and safety profile and has shown superior pre-clinical potency over other SERDs in development. The oral administration of giredestrant has the potential to transform the treatment experience for patients, offering greater convenience and a less painful option compared to therapies administered via intramuscular injection.4,5,9

Giredestrant has a comprehensive development programme across a broad range of settings and treatment combinations for patients with ER-positive, HER2-negative breast cancer. Roche have completed recruitment of patients into a phase II study in second/third-line ER-positive, HER2-negative locally advanced or metastatic breast cancer (acelERA Breast Cancer), and are currently enrolling patients into two phase III studies (persevERA Breast Cancer, lidERA Breast Cancer) evaluating giredestrant across early and metastatic ER-positive, HER2-negative breast cancer settings, as a monotherapy or in combination with palbociclib. In the phase I/II MORPHEUS study giredestrant is being investigated in combination with multiple treatment partners in pre-treated metastatic ER-positive, HER2-negative breast cancer. We are also planning to investigate giredestrant in ER-positive, HER2-positive breast cancer. A standardised once-daily 30 mg dose has been selected for the giredestrant development programme.14,15,16,17

Giredestrant received U.S. Food and Drug Administration Fast Track Designation (FTD) as a second and third-line treatment for ER-positive, HER2-negative, metastatic breast cancer. FTD is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.18

About coopERA Breast Cancer (NCT04436744)19
An open-label, two-arm, phase II study to evaluate the efficacy, safety, and pharmacokinetics of giredestrant versus anastrozole (in the window of opportunity phase) and giredestrant plus palbociclib compared with anastrozole plus palbociclib (in the neoadjuvant phase) in postmenopausal women with untreated, ER-positive, HER2-negative early breast cancer. The primary endpoint of the study is the geometric change in Ki67 scores (a measure of how quickly cancer cells are proliferating) from baseline to week 2 during the window of opportunity phase. Secondary endpoints include complete cell cycle arrest rate, safety outcomes and plasma concentration of giredestrant.

About lidERA Breast Cancer20
An open-label, two-arm, randomised, multicentre, phase III study to evaluate efficacy and safety of adjuvant giredestrant compared with endocrine therapy of physician’s choice in people with medium- and high-risk stage I-III ER-positive, HER2-negative early breast cancer. The primary endpoint of the study is invasive disease-free survival (iDFS), measured from randomisation to the first occurrence of an iDFS event (up to 10 years). Secondary endpoints include overall survival and disease-free survival. LidERA Breast Cancer is currently the only ongoing early breast cancer trial investigating an oral SERD.

About Roche in breast cancer
Roche has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough innovations in HER2-positive and triple-negative breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for all forms of early and advanced breast cancer, including triple-negative and hormone receptor-positive.

Our targeted medicines Herceptin (trastuzumab), Perjeta (pertuzumab), Phesgo, Kadcyla (trastuzumab emtansine) and Tecentriq (atezolizumab) are continuing to transform the treatment of early and advanced HER2-positive and triple-negative breast cancers and, through our clinical programmes, we hope to bring new treatment combinations to people with breast cancer, ultimately improving outcomes.

On December 10, 2021 Eli Lilly and Company (NYSE: LLY) and Regor Therapeutics Group reported that they have entered into a multi-year research collaboration and licensing agreement to discover, develop and commercialize novel therapies for metabolic disorders (Press release, Eli Lilly, DEC 10, 2021, View Source [SID1234596753]).

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Under the terms of the agreement, Lilly will have a license to select Regor intellectual property with an option to extend the license. Lilly will be responsible for clinical development, manufacturing and commercialization worldwide, except for People’s Republic of China, Macau, Hong Kong and Taiwan, where Regor will maintain these rights and responsibilities. The agreement will allow each company the opportunity to fully leverage both parties’ existing compounds and technologies globally to maximize patient treatment choice.

"Through this collaboration, we will have the opportunity to expand treatment options available to patients suffering from metabolic disorders," said Ruth Gimeno, Ph.D., vice president, diabetes research and clinical investigation at Lilly. "Regor’s technology will also allow Lilly to further accelerate innovation and deliver breakthrough therapies in obesity and diabetes."

"In a little over three years, Regor has established a world-class research organization exemplified by our Computer Accelerated Rational Discovery platform. This collaboration is a recognition for Regor’s core technology and research capabilities, but more importantly, it is an extraordinary opportunity to discover, develop and commercialize novel therapeutics to help the millions of patients in the world, "said Xiayang Qiu, Ph.D., founder CEO of Regor. "We are pleased to establish this strategic collaboration with Lilly, a top global leader in metabolic disorders such as diabetes and obesity."

Regor will receive an upfront payment of up to $50 million, which partially includes an equity investment by Lilly in Regor, subject to the parties entering into standard equity agreements. The company is also eligible to receive up to $1.5 billion in potential payments based on the achievement of prespecified preclinical, clinical development and commercial milestones, as well as tiered royalties from low-single to low-double digits on sales resulting from the agreement.

This transaction will be reflected in Lilly’s reported results and financial guidance according to Generally Accepted Accounting Principles (GAAP). There will be no change to Lilly’s 2021 non-GAAP earnings per share guidance as a result of this transaction.

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.