On July 19, 2021 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to COSELA (trilaciclib) investigation for use in combination with chemotherapy for the treatment of locally advanced or metastatic triple negative breast cancer (TNBC) (Press release, G1 Therapeutics, JUL 19, 2021, View Source [SID1234587574]). COSELA is currently being evaluated in PRESERVE 2, a pivotal Phase 3, randomized, double-blind, placebo-controlled study (NCT04799249) in patients receiving first- or second-line gemcitabine and carboplatin chemotherapy for TNBC.

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Fast track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill unmet medical needs. The purpose is to get important new drugs to the patient earlier. A drug that receives Fast Track designation may be eligible for more frequent engagements with the FDA to discuss the drug’s clinical development plan, eligibility for Accelerated Approval and Priority Review, and Rolling Review in which the Company can submit completed sections of its New Drug Application (NDA) for FDA review rather than waiting until every section of the NDA is completed before the entire application can be reviewed.

"Fast Track designation underscores the urgent need for innovative drugs that can significantly improve TNBC patient outcomes," said Raj Malik, M.D., Chief Medical Officer at G1 Therapeutics. "It provides an important pathway to help expedite the development and regulatory review of COSELA in this indication. We look forward to working closely with the FDA as we advance this pivotal program in TNBC and continue to work to unlock the broader potential of this pipeline-in-a-molecule compound that we hope will help patients across multiple tumor types."

About Triple Negative Breast Cancer (TNBC)
According to the American Cancer Society, nearly 300,000 new cases of invasive breast cancer are diagnosed annually in the U.S. Triple-negative breast cancer makes up approximately 15% to 20% of such diagnosed breast cancers. TNBC is cancer that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. Because TNBC cells lack key growth-signaling receptors, patients do not respond well to medications that block estrogen, progesterone, or HER2 receptors. Instead, treating TNBC typically involves chemotherapy, radiation, and surgery. TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer. In general, survival rates tend to be lower with TNBC compared to other forms of breast cancer, and TNBC is also more likely than some other types of breast cancer to return after it has been treated, especially in the first few years after treatment. It also tends to be higher grade than other types of breast cancer.

On July 19, 2021 AstraZeneca reported that it’s Imfinzi (durvalumab) has been approved in China for the 1st-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC), in combination with standard of care platinum chemotherapy (etoposide plus a choice of either carboplatin or cisplatin) (Press release, AstraZeneca, JUL 19, 2021, View Source [SID1234584937]).

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The approval by China’s National Medical Products Administration was based on positive results from the CASPIAN Phase III trial. The trial showed that Imfinzi plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus chemotherapy alone. In addition, results from the China cohort of patients were consistent with the global results.

Small cell lung cancer (SCLC) is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly despite initial response to chemotherapy.1,2 Prognosis is particularly poor, as only 7% of all SCLC patients and 3% of those with extensive-stage disease will be alive five years after diagnosis.3

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "Today’s approval of Imfinzi plus chemotherapy brings an important global standard of care to patients with extensive-stage small cell lung cancer in China, who have had few treatment options and a dire prognosis. Physicians can now offer these patients a well-tolerated immunotherapy regimen with sustained overall survival and prolonged treatment response, as well as convenient dosing. This is also the first time physicians have had the choice to combine immunotherapy with cisplatin, a preferred chemotherapy in this setting in China."

The CASPIAN Phase III trial met the primary endpoint of OS for Imfinzi plus chemotherapy in June 2019, reducing the risk of death by 27% versus chemotherapy alone (based on a hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.59-0.91; p=0.0047), with a median OS of 13.0 months versus 10.3 months for chemotherapy alone. These results were published in The Lancet in October 2019.4 Results also showed an increased confirmed objective response rate for Imfinzi plus chemotherapy (68% versus 58% for chemotherapy alone). Imfinzi added to chemotherapy delayed the time for disease symptoms to worsen.4

An updated analysis showed sustained efficacy for Imfinzi plus chemotherapy after a median follow up of more than two years (OS HR of 0.75; 95% CI 0.62-0.91; nominal p=0.0032), with median OS of 12.9 months versus 10.5 months for chemotherapy alone. An estimated 22.2% of patients treated with Imfinzi plus chemotherapy were alive at 24 months versus 14.4% for chemotherapy alone. The safety and tolerability for Imfinzi and chemotherapy were consistent with the known safety profiles of these medicines. No patients tested positive for treatment-emergent anti-drug antibodies to Imfinzi.

Safety and efficacy results in the China cohort of patients were consistent with results in the overall global trial population. Detailed results from this cohort will be presented at a forthcoming medical meeting.

The CASPIAN Phase III trial used a fixed dose of Imfinzi (1500mg) administered every three weeks for four cycles while in combination with chemotherapy and then every four weeks as a monotherapy until disease progression. Based on the trial results, Imfinzi, in combination with etoposide and either carboplatin or cisplatin, is approved in the 1st-line setting of ES-SCLC in more than 55 countries, including the US, Japan and across the EU.

Imfinzi is also being tested following concurrent chemoradiation therapy in patients with limited-stage SCLC in the ADRIATIC Phase III trial as part of a broad development programme. In addition, Imfinzi is also approved to treat non-small cell lung cancer (NSCLC) in the curative-intent setting of unresectable, Stage III disease after chemoradiation therapy in the US, Japan, China, across the EU and in many other countries, based on results from the PACIFIC Phase III trial.

Small cell lung cancer
Lung cancer is the leading cause of cancer death among men and women and accounts for about one-fifth of all cancer deaths.5 Lung cancer is broadly split into NSCLC and SCLC, with about 15% classified as SCLC.6 About two-thirds of SCLC patients are diagnosed with extensive-stage disease, in which the cancer has spread widely through the lung or to other parts of the body.3

CASPIAN
CASPIAN was a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of 805 patients with ES-SCLC. The trial compared Imfinzi in combination with etoposide and either carboplatin or cisplatin platinum chemotherapy, or Imfinzi and chemotherapy with the addition of a second immunotherapy, tremelimumab, versus chemotherapy alone. In the two experimental arms, patients were treated with four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and optional prophylactic cranial irradiation.

The trial was conducted in more than 200 centres across 23 countries, including the US, Europe, South America, Asia and the Middle East. The primary endpoint was OS in each of the two experimental arms. In June 2019, AstraZeneca announced the CASPIAN Phase III trial had met one primary endpoint of demonstrating OS for Imfinzi plus chemotherapy at a planned interim analysis. In March 2020, however, it was announced that the second experimental arm with tremelimumab did not meet its primary endpoint of OS.

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

In addition to approvals in ES-SCLC and unresectable, Stage III NSCLC, Imfinzi is approved for previously treated patients with advanced bladder cancer in several countries. Since the first approval in May 2017, more than 100,000 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 NSCLC, SCLC, bladder cancer, hepatocellular carcinoma, biliary tract cancer (a form of liver cancer), oesophageal cancer, gastric and gastroesophageal cancer, cervical cancer, ovarian cancer, endometrial cancer, and other solid tumours.

AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and tremelimumab; Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

AstraZeneca in immunotherapy
Immunotherapy is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s IO portfolio is anchored in immunotherapies that have been designed to overcome anti-tumour immune suppression. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a single treatment and in combination with tremelimumab and other novel antibodies in multiple tumour types, stages of disease, and lines of treatment, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, small, targeted molecules from across AstraZeneca’s oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On July 19, 2021 Oblato, Inc. (the Company) reported that it has received an agreement from the FDA for its plan to submit an intermediate size expanded access protocol for use of OKN-007 in patients with high-grade gliomas (Press release, Oblato, JUL 19, 2021, View Source [SID1234584954]). The company is already developing OKN-007 as a treatment of glioblastoma multiforme.

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In a December 2020 meeting with the FDA, the agency agreed to Oblato’s plan to initiate a clinical trial for diffuse intrinsic pontine glioma (DIPG) pediatric patients, a rare and difficult to treat brain cancer. Currently, the Company is in discussion for this trial with a consortium consisting of pediatric cancer hospitals. The eligible patients who can participate in this clinical trial for pediatric DIPG must meet specific inclusion and exclusion criteria.

Unfortunately, there are many additional patients with similar aggressive gliomas with a poor prognosis and some of these patients will not have access this treatment as they are not eligible for the clinical trial or are unable to get to the clinical trial sites. Based on this difficult situation faced by many patients who have various life-threatening malignant gliomas including DIPG, Oblato recently received an agreement from the FDA that OKN-007 can be administered outside of the clinical trial to both pediatric and adult patients diagnosed with several types of high-grade gliomas under an intermediate size expanded access program (iEAP). The FDA recommended that the Oblato submit a complete protocol for FDA review and feedback. The Company will submit the protocol as soon as possible to initiate the iEAP.

Expanded access refers to a pathway in which patients with serious or life-threatening diseases with no available treatment options may gain access to investigational medical products, which are either under development or have not yet received marketing approved. In particular, iEAPs are used for a wide range of patients in a number of medical institutions. Pediatric and adult patients who will be eligible for the iEAP using OKN-007 include those with gliomas similar to DIPG involving the thalamus, hypothalamus, brain stem, pons, bone marrow, or spinal cord, or midline tumors including malignant gliomas, gangliocytoma, and anaplastic astrocytoma morphologies.

Regarding the iEAP, an official from the Company stated that "After we released the news regarding the development of our new DIPG treatment, several DIPG patient families reached out to the Company asking to participate in the clinical trial. Since DIPG and other gliomas progress rapidly, Oblato wanted to make the treatment available as quickly as possible and to as many of these patients as possible. The Company decided to use the iEAP first to give an opportunity for patients with either DIPG or high-grade gliomas for which there is either no effective treatment or they are ineligible to participate in a clinical trial. Using the iEAP, Oblato can administer our investigational medicinal product even before we initiate the clinical trial. Currently, we are in discussion with a firm experienced with the iEAP and plan to submit the protocol for the iEAP to the FDA as soon as possible."

"iEAP not only meets the target to provide treatment opportunities to patients, but accords with our company’s GBM and DIPG development strategy. There are a number of new orphan drugs that were approved using the clinical data obtained through an iEAP. An iEAP can also be one way to determine the potential benefit and risk through treatment outcomes with various types of patients," stated an official from the Company regarding the strategic background.

On July 19, 2021 HCW Biologics Inc. (NASDAQ:HCWB) (the "Company"), an innovative preclinical stage biopharmaceutical company focused on discovering and developing novel immunotherapies to lengthen health span by disrupting the link between chronic, low-grade inflammation and age-related diseases, reported the pricing of an underwritten initial public offering of 7,000,000 shares of common stock at a public offering price of $8.00 per share for gross proceeds of approximately $56.0 million, prior to deducting underwriting discounts, commissions, and other offering expenses. All of the shares of common stock are being offered by the Company (Press release, HCW Biologics, JUL 19, 2021, View Source [SID1234585180]). The shares are expected to begin trading on the Nasdaq Global Market on July 20, 2021, under the ticker symbol "HCWB". The offering is expected to close on or about July 22, 2021, subject to satisfaction of customary closing conditions. In addition, the Company has granted the underwriters a 45-day option to purchase up to an additional 1,050,000 shares at the public offering price less the underwriting discounts and commissions.

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EF Hutton, division of Benchmark Investments, LLC, is acting as sole book-running manager for the offering. Revere Securities LLC is acting as co-manager for the offering.

A registration statement relating to these securities was declared effective by the U.S. Securities and Exchange Commission (SEC) on July 19, 2021. A final prospectus relating to this offering will be filed with the SEC. The offering is being made only by means of a prospectus, copies of which may be obtained, when available, from: EF Hutton, division of Benchmark Investments, LLC, 590 Madison Avenue, 39th Floor, New York, NY 10022, Attention: Syndicate Department, or via email at [email protected] or telephone at (212) 404-7002.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, 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.

On July 19, 2021 Compugen Ltd. (Nasdaq: CGEN), a clinical-stage cancer immunotherapy company and a leader in predictive target discovery, reported that the first patient has been dosed in the cohort expansion arm of the Phase 1/2 study evaluating the triple combination of COM701, Compugen’s first-in-class anti-PVRIG antibody, with Opdivo (nivolumab) and Bristol Myers Squibb’s investigational anti-TIGIT antibody, BMS-986207 (Press release, Compugen, JUL 19, 2021, View Source [SID1234584955]).

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"We continue to push forward as leaders in the DNAM axis space and as the only company evaluating a potential synergistic triple blockade of PVRIG, TIGIT and PD-1 in the clinic," said Anat Cohen-Dayag, Ph.D., President and CEO of Compugen. "We believe that the future of immuno-oncology will be driven by combination therapy and this study examining our three-pathway hypothesis is an important component of our overall strategy and a key differentiator for Compugen in the TIGIT space. The study is designed to evaluate simultaneous blockade of three immune checkpoint pathways, PVRIG, TIGIT and PD-1 and test the hypothesis that blockade of both PVRIG and TIGIT, parallel DNAM pathways, may be required in certain tumor types to generate or enhance an anti-tumor immune response. The initiation of the cohort expansion phase of the study, allowing us to focus with the selected dose for expansion on specific patient populations where we believe the DNAM axis is dominant, is an important step to examine the potential benefit of this unique immunotherapy combination in a broader range of patients. We are on track to report preliminary data from the triple combination dose escalation arm of the study in the fourth quarter of this year."

Dr. Cohen-Dayag added, "We are delighted to have Bristol Myers Squibb as our partner in this study and are pleased to have their continued support and commitment to the collaboration."

The open-label Phase 1/2 trial is designed to evaluate the safety, tolerability, and preliminary antitumor activity of COM701 in combination with Opdivo and BMS-986207. Additional information is available at www.clinicaltrials.gov (NCT04570839).

Opdivo is a trademark of Bristol-Myers Squibb Company.

About COM701

COM701 is a humanized antibody that binds with high affinity to PVRIG, a novel immune checkpoint discovered computationally by Compugen, blocking the interaction with its ligand, PVRL2. Blockade of PVRIG by COM701 has demonstrated in preclinical studies potent, reproducible enhancement of T cell activation, consistent with the desired mechanism of action of activating T cells in the tumor microenvironment to generate anti-tumor immune responses. Compugen has identified PVRIG and TIGIT as key parallel and complementary inhibitory pathways in the DNAM axis, which also intersect with the well-established PD-1 pathway. Research from Compugen suggests that these three pathways have different dominance in different tumor types and patients, implying that to induce effective antitumor responses, certain patient populations may require the blockade of different combinations of these three pathways. To test this hypothesis, Compugen has established a science-driven, biomarker informed clinical program, which evaluates different combinations of these axis members across tumor types. Compugen is the only company with clinical assets targeting both PVRIG and TIGIT in its portfolio allowing it to more fully exploit the potential of blocking these parallel and complementary members of the DNAM axis to drive robust immune responses.