On January 19, 2024 Astrazeneca reported that Positive results from the EMERALD-1 Phase III trial showed Imfinzi (durvalumab) in combination with TACE and bevacizumab demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS) compared to TACE alone in patients with hepatocellular carcinoma (HCC) eligible for embolisation (Press release, AstraZeneca, JAN 19, 2024, View Source [SID1234639367]).

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These results will be presented today at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco, California (#LBA432).

Approximately 20-30% of patients with HCC, the most common type of liver cancer, are eligible for embolisation, a procedure that blocks the blood supply to the tumour and can also deliver chemotherapy or radiation therapy directly to the liver.1-8 Despite being the standard of care in this setting, most patients who receive embolisation experience disease progression or recurrence within eight months.9-11

In EMERALD-1, treatment with Imfinzi plus TACE and bevacizumab reduced the risk of disease progression or death by 23% compared to TACE alone (based on a hazard ratio [HR] of 0.77; 95% confidence interval [CI] 0.61-0.98; p=0.032). Median PFS was 15 months in patients treated with the Imfinzi combination versus 8.2 months with TACE. The PFS benefit observed was generally consistent across key prespecified subgroups. The secondary endpoint of time to progression (TTP) further supports the clinical benefit of Imfinzi plus TACE and bevacizumab in this setting, with a median TTP of 22 months versus 10 months for TACE (HR 0.63; 95% CI 0.48-0.82).

The trial will continue as planned to assess the key secondary endpoint of overall survival (OS).

Bruno Sangro, MD, PhD, Director of the Liver Unit and Professor of Medicine at Clínica Universidad de Navarra, Pamplona, Spain and a lead investigator in the EMERALD-1 trial, said: "In this earlier liver cancer setting, embolisation alone has been the standard of care for more than 20 years, and rates of disease progression have remained high. Adding durvalumab and bevacizumab to TACE reduced the risk of disease progression or death by twenty-three per cent for patients with liver cancer eligible for embolisation, showing for the first time that combining a systemic treatment with TACE meaningfully improves this clinically relevant outcome in earlier-stage disease."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "With Imfinzi-based treatment, patients with liver cancer eligible for embolisation lived nearly seven additional months before their disease progressed. We are discussing these positive EMERALD-1 data with global regulatory authorities while awaiting the final overall survival results from the trial."

Summary of results: EMERALD-1i

Imfinzi plus TACE and bevacizumab

(n=204)

Placebo plus TACE

(n=205)

Median PFS (months; 95% CI)ii, iii

15.0 (11.1-18.9)

8.2 (6.9-11.1)

PFS HR (95% CI)ii, iv

0.77 (0.61-0.98)

p-valuev

0.032

PFS rate at 12 months (%)iii

55.5

39.8

PFS rate at 18 months (%)iii

43.1

28.3

Median TTP (months; 95% CI)iii, v

22.0 (16.6-24.9)

10.0 (7.1-13.6)

TTP HR (95% CI)iv, v

0.63 (0.48-0.82)

Subjects with measurable disease

Imfinzi plus TACE and bevacizumab

(n=202)

Placebo plus TACE

(n=203)

Objective Response Rate (ORR) (%)iii

43.6

29.6

i The data cut-off date was 11 Sep 2023.

ii PFS, TTP and ORR by Blinded Independent Central Review (BICR) per RECIST v1.1

iii Calculated using Kaplan-Meier method

iv Calculated from stratified Cox proportional hazards method

v The threshold of significance for this analysis was 0.0435 based on the alpha spend at the PFS interim analysis (2.27%) and the actual number of events at PFS final analysis.

The safety profile for Imfinzi plus TACE and bevacizumab was generally manageable and consistent with the known profile of each medicine. The number of TACE procedures was consistent across arms. No new safety signals were observed. Grade 3 and 4 adverse events due to any cause occurred in 45.5% of patients treated with Imfinzi plus TACE and bevacizumab and 23% of patients treated with TACE alone.

Notes

Liver cancer
Liver cancer, of which HCC is the most common type, is the third-leading cause of cancer death, with an estimated 900,000 people worldwide diagnosed each year and a high prevalence in certain regions of Asia.12-14 An estimated 80-90% of all patients with HCC also have cirrhosis.15 Chronic liver diseases such as cirrhosis are associated with inflammation that over time can lead to the development of HCC.15 Immunotherapy is a proven treatment modality in HCC with approved options available for patients in later-line settings.16

EMERALD-1
EMERALD-1 is a randomised, double-blind, placebo-controlled, multicentre, global Phase III trial of Imfinzi plus TACE concurrently, followed by Imfinzi with or without bevacizumab until progression versus TACE alone in a total of 616 patients with unresectable HCC eligible for embolisation.

The trial was conducted in 157 centres across 18 countries, including in North America, Australia, Europe, South America and Asia. The primary endpoint was PFS for Imfinzi plus TACE and bevacizumab versus TACE alone, and secondary endpoints include PFS for Imfinzi plus TACE, OS, patient-reported outcomes and ORR.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer (BTC) and in combination with Imjudo (tremelimumab) in unresectable HCC in the US, EU, Japan, China and many other countries based on the TOPAZ-1 and HIMALAYA Phase III trials, respectively. Following HIMALAYA in the advanced setting, EMERALD-1 is AstraZeneca’s second positive Phase III trial in HCC.

In non-small cell lung cancer (NSCLC), Imfinzi is approved in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC in the US, EU and Japan based on the POSEIDON Phase III trial. Imfinzi is also the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiation therapy based on the PACIFIC Phase III trial, the results of which have been confirmed in the real-world setting in the PACIFIC-R study. In 2023, AstraZeneca announced positive results from the AEGEAN Phase III trial evaluating Imfinzi in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery in resectable NSCLC.

Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small cell lung cancer (SCLC) based on the CASPIAN Phase III trial. Imfinzi is approved in previously treated patients with advanced bladder cancer in a small number of countries.

Since the first approval in May 2017, more than 200,000 patients have been treated with Imfinzi.

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several GI cancers, breast cancer and other solid tumours. In 2023, AstraZeneca announced positive results for several Phase III trials evaluating Imfinzi in various combinations, including in ovarian (DUO-O) and endometrial (DUO-E) cancers with Lynparza (olaparib).

In GI cancers specifically, AstraZeneca has an extensive clinical development programme further assessing Imfinzi across multiple settings. In addition to EMERALD-1, Imfinzi is also being investigated in combination with bevacizumab in adjuvant HCC (EMERALD-2), in combination with Imjudo, lenvatinib and TACE in embolisation-eligible HCC (EMERALD-3), in resectable gastric and gastroesophageal junction cancers (MATTERHORN) and in locally advanced oesophageal cancer (KUNLUN). In June 2023, Imfinzi added to standard-of-care neoadjuvant chemotherapy met a key secondary endpoint of pathologic complete response in the MATTERHORN Phase III trial.

On January 19, 2024 Novartis reported data from the Phase III NETTER-2 trial showing that Lutathera (INN: lutetium (177Lu) oxodotreotide / USAN: lutetium Lu 177 dotatate) plus long-acting release (LAR) octreotide reduced the risk of disease progression or death by 72% as first-line therapy in patients with somatostatin receptor-positive (SSTR+) well-differentiated grade 2/3 advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) versus high-dose octreotide LAR alone (Press release, Novartis, JAN 19, 2024, View Source [SID1234639366]). Data were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (GI) Cancers Symposium.

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"These positive results for Lutathera are practice-changing and offer new first-line treatment data for patients who have a significant unmet need. This study confirms the clinical benefit of first-line radioligand therapy for newly diagnosed patients living with these types of advanced GEP-NETs," said Dr. Simron Singh, Associate Professor of Medicine at the University of Toronto and cofounder of the Susan Leslie Clinic for Neuroendocrine Tumours at the Odette Cancer Centre, Sunnybrook Health Sciences Centre, Ontario, Canada. "These findings should instill confidence among physicians in using Lutathera as a first-line treatment for patients with this life-threatening type of cancer."

Efficacy endpoint1 Lutathera plus octreotide LAR vs. high-dose octreotide LAR
Progression-free survival HR 0.28 (95% CI: 0.18, 0.42; p<0.0001)
Median PFS (months) 22.8 month (95% CI: 19.4 -not estimable) vs. 8.5 months (95% CI: 7.7-13.8)
Objective response rate (ORR)* 43% (95% CI: 35.0-51.3) vs. 9.3% (95% CI: 3.8-18.3), p<0.0001
*Assessed via RECIST 1.1
"This is the first positive Phase III trial of a radioligand therapy in the first-line setting, and the overall efficacy and safety results are amongst the most clinically relevant observed to date in this kind of advanced cancer, addressing a significant unmet need for patients with newly diagnosed advanced GEP-NETs," said Jeff Legos, Global Head of Oncology Development at Novartis. "The positive results are a significant advancement and further reaffirm our strategy to research and develop radioligand therapies in earlier lines of treatment or stages of disease to improve outcomes for patients."

No new or unexpected safety findings were observed in the study and data are consistent with the already well-established safety profile of Lutathera1. Most patients (88%) in the Lutathera arm received all four cycles of Lutathera treatment. The most common all-grade AEs (≥20%) for the Lutathera arm vs. control arm were nausea (27.2% vs 17.8%), diarrhea (25.9% vs 34.2%) and abdominal pain (17.7% vs 27.4%), and the most common grade ≥3 AE (>5%) was lymphocyte count decreased (5.4% vs 0%).

NETs are a type of cancer that originate in neuroendocrine cells throughout the body and are commonly considered slow-growing malignancies. However, some NETs are associated with rapid progression and poor prognosis and in many cases, diagnosis is delayed until patients have advanced disease2-4. Even though NETs are a rare (orphan) disease, their incidence has increased over the past several decades2-5 and there is a need for continued research into treatment options for newly diagnosed patients.

The NETTER-2 trial is ongoing for further evaluation of secondary endpoints including overall survival and long-term safety.

About NETTER-2
NETTER-2 (NCT03972488) is an open-label, multi-center, randomized, comparator-controlled Phase III trial assessing whether Lutathera plus octreotide LAR when taken as a first-line treatment can prolong PFS in patients with high-proliferation rate tumors (G2 and G3), compared to treatment with high-dose (60 mg) long-acting octreotide6. Eligible patients were diagnosed with SSTR-positive advanced GEP-NETs within 6 months before enrollment6.

About Lutathera
Lutathera (INN: lutetium (177Lu) oxodotreotide / USAN: lutetium Lu 177 dotatate) is approved in the US for the treatment of adult patients with SSTR-positive GEP-NETs, including those in the foregut, midgut and hindgut, an indication which includes the NETTER-2 population. Lutathera is also approved in Europe for unresectable or metastatic, progressive, well-differentiated (G1 and G2), SSTR-positive GEP-NETs in adults7,8, and in Japan for SSTR-positive NETs.

On January 19, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that it will hold its fourth-quarter and full-year 2023 sales and earnings conference call with institutional investors and analysts at 9:00 a.m. ET on Thursday, Feb. 1 (Press release, Merck & Co, JAN 19, 2024, View Source [SID1234639365]). During the call, company executives will provide an overview of Merck’s performance for the fourth quarter and outlook for 2024.

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Investors, journalists and the general public may access a live audio webcast of the call via this weblink. A replay of the webcast, along with the sales and earnings news release, supplemental financial disclosures, and slides highlighting the results, will be available at www.merck.com.

All participants may join the call by dialing (800) 779-6561 (U.S. and Canada Toll-Free) or (773) 756-4619 and using the access code 5958465.

On January 19, 2024, IDEAYA Biosciences, Inc. (the "Company") entered into an Open Market Sales Agreement (the "Sales Agreement") with Jefferies LLC ("Jefferies"), with respect to an at-the-market offering program under which the Company may offer and sell, from time to time at its sole discretion, shares of its common stock, par value $0.0001 per share (the "Common Stock"), having aggregate gross proceeds of up to $350.0 million (the "Shares") through Jefferies as its sales agent (Filing, 8-K, Ideaya Biosciences, JAN 19, 2024, View Source [SID1234639364]).

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Under the Sales Agreement, the Company will set the parameters for the sale of Shares, including the number of Shares to be issued, the time period during which sales are requested to be made, limitations on the number of Shares that may be sold in any one trading day and any minimum price below which sales may not be made. Subject to the terms of the Sales Agreement, Jefferies may sell the Shares by any method that is deemed to be an "at the market offering" as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended (the "Securities Act"), including sales made directly on The Nasdaq Global Select Market or any other trading market for the Common Stock. The Company will pay Jefferies a commission of up to three percent (3.0%) of the gross sales proceeds of any Shares sold through Jefferies under the Sales Agreement, and has provided Jefferies with customary indemnification and contribution rights. The Sales Agreement will terminate upon the earlier of (i) the sale of all Shares subject to the Sales Agreement or (ii) termination of the Sales Agreement in accordance with its terms.

Any Shares to be offered and sold under the Sales Agreement will be issued and sold pursuant to the Company’s Registration Statement on Form S-3 (File No. 333-272936), which became automatically effective upon its filing on June 26, 2023. The Company filed a prospectus supplement with the Securities and Exchange Commission on January 19, 2024 in connection with the offer and sale of the Shares pursuant to the Sales Agreement.

The foregoing description of the Sales Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Sales Agreement, a copy of which is furnished as Exhibit 1.1 to this Current Report on Form 8-K (this "Current Report") and is incorporated herein by reference.

Latham & Watkins LLP, counsel to the Company, has issued an opinion to the Company, dated January 19, 2024, relating to the validity of the Shares to be issued and sold pursuant to the Sales Agreement, a copy of which is filed as Exhibit 5.1 to this Current Report.

This Current Report shall not constitute an offer to sell or the solicitation of an offer to buy any Shares, nor shall there be any offer, solicitation or sale of the Shares in any state or country in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or country.

On January 19, 2024 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, reported the closing of its underwritten public offering of shares of its common stock. Alector sold 10,869,566 shares of its common stock in the offering (Press release, Alector, JAN 19, 2024, View Source [SID1234639363]). Alector has granted the underwriter a 30-day option to purchase up to an additional 1,630,434 shares of its common stock. The gross proceeds to Alector from the offering, before deducting underwriting discounts and commissions and estimated offering expenses, are approximately $75 million.

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Cantor Fitzgerald & Co. acted as sole book-running manager for the offering.

The offering was made pursuant to a shelf registration statement on Form S-3 (File No. 333- 270126) that was previously filed with and subsequently declared effective by the Securities and Exchange Commission ("SEC") on May 1, 2023. The offering was made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. The final prospectus supplement and accompanying prospectus relating to the offering have been filed with the SEC and are available on the SEC’s website at View Source Copies of the final prospectus supplement and the accompanying prospectus relating to the offering may be obtained from: Cantor Fitzgerald & Co., Attention: Capital Markets, 110 East 59th Street, 6th Floor, New York, NY 10022, or by e-mail at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of, these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.