On December 7, 2022 GSK plc (LSE/NYSE: GSK) reported results from the PERLA phase II clinical trial investigating dostarlimab in combination with chemotherapy versus pembrolizumab in combination with chemotherapy as a first-line treatment for patients with metastatic non-squamous non-small cell lung cancer (NSCLC) (Press release, GlaxoSmithKline, DEC 7, 2022, View Source [SID1234624892]). Dostarlimab plus chemotherapy achieved very promising results for the primary endpoint of confirmed objective response rate (ORR) as well as for the key secondary endpoint of median progression-free survival (mPFS).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The PERLA phase II trial is a randomised, double-blind trial of 243 patients and is the largest global head-to-head trial of programmed death receptor-1 (PD-1) inhibitors in this patient population. The findings from the primary analysis were presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress 2022 in Geneva, Switzerland.

Hesham Abdullah, Senior Vice President, Global Head of Oncology Development, GSK said: "The head-to-head data from the PERLA trial showed that dostarlimab combined with chemotherapy provided robust anti-tumour activity in patients with previously untreated metastatic non-squamous non-small cell lung cancer. The positive results from this trial inform our future development plans and highlight the potential for dostarlimab to be our foundational immuno-oncology therapy as a single-agent and in combination with standards of care and novel therapies within our pipeline."

The primary endpoint was overall ORR by Response Evaluation Criteria in Solid Tumours (RECIST) as determined by blinded independent central review (BICR) and was 46% (n=56/121) in the dostarlimab treatment arm versus 37% (n=45/122) in the pembrolizumab treatment arm (difference in ORR: 9.32%; 80% CI: 1.46% to 17.18%).

The key secondary endpoint, mPFS, was 8.8 months (95% CI: 6.7 to 10.4) in the dostarlimab treatment arm versus 6.7 months (95% CI: 4.9 to 7.1) in the pembrolizumab treatment arm (HR 0.70 [95% CI: 0.50 to 0.98]).

The table below summarizes key results across all pre-specified programmed death ligand-1 (PD-L1) expression cohorts, as measured by Tumor Proportion Score (TPS).

ORR by RECIST (BICR)
(95% CI)

mPFS (Investigator Assessed)
(95% CI)
PFS HR
(95% CI)

Pre-specified PD-L1 expression cohorts measured by TPS

dostarlimab
+ chemo

pembrolizumab
+ chemo

dostarlimab
+ chemo
(CI)

pembrolizumab
+ chemo
(CI)

Overall
Population

46%
(37.2-55.6)

37%
(28.3-46.1)

8.8 months
(6.7-10.4)

6.7 months
(4.9-7.1)

HR 0.70
(0.50-0.98)

TPS < 1%

28%

33%

7.0 months
(4.9-9.7)

6.9 months
(4.7-9.6)

0.77
(0.46-1.28)

TPS ≥ 1%

59%

39%

10.4 months
(6.8-13.6)

6.1 months
(4.8-7.1)

0.66
(0.41-1.03)

TPS 1% to 49%

50%

34%

9.0 months
(5.3-NR)

5.4 months
(3.2-11.3)

0.67
(0.38-1.19)

TPS ≥ 50%

74%

48%

10.4 months
(5.8-NR)

6.7 months
(4.2-NR)

0.60
(0.27-1.29)

Treatment-emergent adverse events (TEAEs) for dostarlimab in the PERLA phase II trial were consistent with previous trials of similar regimens. The rate of TEAEs was 97% for both the dostarlimab and pembrolizumab treatments arms of the trial. The rate of Grade 3 or higher TEAEs was 59% in the dostarlimab treatment arm and 60% in the pembrolizumab treatment arm. The most common TEAEs were anaemia, asthenia, nausea, constipation, cough, dyspnoea, vomiting, decreased appetite, and neutropenia.

Solange Peters, M.D., Ph.D., Professor and Chair of Medical Oncology, University Hospital of Lausanne, Switzerland and ESMO (Free ESMO Whitepaper) President, said: "Understanding the role of immuno-oncology treatments in the NSCLC patient population is a significant goal we’re committed to in the oncology community. Despite advancements in treatment options, unmet need persists for health care providers and their patients. The data results presented at ESMO (Free ESMO Whitepaper)-IO add to the body of evidence of immuno-oncology agents such as dostarlimab and enhance our knowledge in this important area of research."

GSK is also studying dostarlimab in earlier lines of treatment for endometrial cancer and in combination with other therapeutic agents for patients with advanced/metastatic cancers. This research includes the recently announced positive headline RUBY Phase III trial results in patients with primary advanced or recurrent endometrial cancer, as well as the COSTAR Lung phase III trial comparing cobolimab, an investigational anti-TIM-3 targeting monoclonal antibody, plus dostarlimab plus docetaxel to dostarlimab plus docetaxel to docetaxel alone in patients with advanced NSCLC who have progressed on prior anti-PD-(L)1 therapy and chemotherapy.

About PERLA

The PERLA phase II trial is a global, randomised, double-blind trial of 243 patients evaluating the efficacy and safety of dostarlimab plus chemotherapy versus pembrolizumab plus chemotherapy in patients with metastatic non-squamous NSCLC without a known sensitising epidermal growth factor receptor, anaplastic lymphoma kinase, or receptor tyrosine kinase-1 mutation, V600E mutation of the BRAF gene or other genomic mutation for which an approved targeted therapy is available. The primary endpoint was objective response rate of dostarlimab plus chemotherapy versus pembrolizumab plus chemotherapy assessed by blinded independent central review per RECIST v1.1. Secondary endpoints include investigator-assessed progression-free survival per RECIST v1.1, overall survival, and safety.

About NSCLC

Lung cancer is one of the most commonly diagnosed cancers worldwide, with more than 2 million new cases diagnosed globally in 2020.1 It is the most common cause of cancer-related death in men and women worldwide, with relatively poor survival outcomes as evidenced by a five-year survival rate of 21%.2 Approximately 85% of lung cancer cases are NSCLC.3,4 NSCLC develops when once-healthy cells in the lungs begin to grow abnormally and form a tumour. When NSCLC spreads, or metastasizes, it can become more difficult treat, resulting in a significant need for new treatment approaches.

About Jemperli (dostarlimab)

Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2. Jemperli is being investigated in registrational enabling studies, as monotherapy and as part of combination regimens, including in women with recurrent or primary advanced endometrial cancer, women with stage III or IV non-mucinous epithelial ovarian cancer, and in patients with other advanced solid tumours or metastatic cancers. Jemperli is not approved anywhere in the world in combination with chemotherapy in first-line patients with metastatic non-squamous NSCLC or in combination with other agents to treat patients with advanced NSCLC who have progressed on prior anti-PD-L1 therapy and chemotherapy.

Jemperli was discovered by AnaptysBio and licensed to TESARO, Inc., under a Collaboration and Exclusive License Agreement signed in March 2014. The collaboration has resulted in three monospecific antibody therapies that have progressed into the clinic. These are: Jemperli (GSK4057190), a PD-1 antagonist; cobolimab, (GSK4069889), a TIM-3 antagonist; and GSK4074386, a LAG-3 antagonist. GSK is responsible for the ongoing research, development, commercialization, and manufacturing of each of these Products under the Agreement.

Important Information for Jemperli in the EU

Indication

Jemperli is indicated as monotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability high (MSI H) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum containing regimen.

Refer to the Jemperli Reference Information for a full list of adverse events and the complete important safety information in the EU.

On December 7, 2022 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported initial results from a 24 patient Phase 2 mechanism of action (MOA) trial showing favorable alterations in the tumor microenvironment from a single dose of trilaciclib monotherapy as measured by increases in the proportions of CD8+ T cells compared to T regulatory cells (Tregs) in patients with early-stage triple negative breast cancer (TNBC) (Press release, G1 Therapeutics, DEC 7, 2022, View Source [SID1234624891]). These initial study results are being presented in a poster session at the annual San Antonio Breast Cancer Symposium (SABCS), December 6 – 10, 2022.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The initial goal of this trial is to confirm our understanding of the trilaciclib immune mechanism by evaluating changes in the tumor immune microenvironment in a clinical setting following a single dose of trilaciclib," said Raj Malik, M.D., Chief Medical Officer at G1 Therapeutics. "These are the first data to show the beneficial effect of a single dose of trilaciclib, one week after administration, on the tumor microenvironment. These results show that trilaciclib monotherapy can improve the ratio of CD8+ T cells to Tregs and thus may enhance the overall antitumor immune response and confirm the trends we observed in preclinical studies and in peripheral blood in our Phase 2 trial in TNBC. We look forward to the pathologic complete response data in the second quarter of 2023 which we believe will clarify the ability of trilaciclib to improve anti-tumor efficacy for TNBC patients in this early-stage treatment setting, particularly in combination with a checkpoint inhibitor."

Initial Phase 2 Results (n=24)

In the ongoing neoadjuvant Phase 2 study, newly diagnosed TNBC patients underwent a tumor biopsy at baseline and again 7 days after receiving a single dose of trilaciclib monotherapy to elucidate the MOA of trilaciclib in the tumor microenvironment, independent of chemotherapy. Evaluable paired biopsies were available for 23 patients. The treatment phase of this trial was initiated after the on-treatment (second) tumor biopsy and included trilaciclib administered in combination with dose-dense anthracycline cyclophosphamide/ taxane with the option to add pembrolizumab and/or carboplatin. Twenty-one (88%) patients received the checkpoint inhibitor pembrolizumab in addition to chemotherapy starting at cycle 1, and 17 (71%) patients received carboplatin starting at cycle 5. As of the cutoff date (9/21/22), patients had received a median (range) of 7 (3–16) cycles of treatment, and 19 (79%) patients had completed at least four cycles of treatment.

Results one week after a single dose of trilaciclib show a trend toward an increased ratio of CD8+ T-cells to Tregs within the tumor microenvironment, indicating trilaciclib may favorably modulate the composition of immune cells to support antitumor immune responses. Tumor biopsies from most patients showed the trend at the time point that was evaluated.

Initial safety and tolerability results from the treatment phase are also encouraging, and consistent with historical safety data from the standard of care neoadjuvant regimen with potential observed reductions in certain hematologic adverse events. There were no instances of grade 3/4 diarrhea in patients receiving trilaciclib in this trial.

Phase 2 Trial Design

This is a Phase 2 multicenter, open-label, single-arm, neoadjuvant study. Tumor tissue was obtained at baseline prior to study drug administration. Patients then received a single dose of monotherapy (240 mg/m2) trilaciclib, followed by a tumor biopsy approximately one week later to assess the ability of a single dose of trilaciclib monotherapy to favorably alter the tumor microenvironment. Patients then entered the treatment phase in which trilaciclib is administered on day 1 of each cycle of anthracycline/cyclophosphamide for four cycles followed by trilaciclib administered on day 1 of each weekly cycle of taxane chemotherapy for 12 cycles. Pembrolizumab and/or carboplatin was added at the discretion of the investigator. Three to five weeks after the treatment phase, patients will have curative surgery and a final tumor tissue sample will be collected if the patient has residual disease.

The primary objective is to evaluate the immune-based mechanism of action of a single dose of trilaciclib as measured by the change in the ratio of CD8+ tumor-infiltrating lymphocytes (TILs) to regulatory T cell (Tregs) in the tumor microenvironment. Secondary endpoints include assessment of pathologic complete response (pCR) rate at the time of definitive surgery, and safety of the combination of trilaciclib with neoadjuvant chemotherapy regimen; exploratory endpoints include assessment of the immune response, and identification of molecular and cellular biomarkers in tumor or blood samples that may be indicative of clinical response/resistance, pharmacodynamic activity, and/or the mechanism of action of trilaciclib.

Nonclinical studies presented at the 2022 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference

The new Phase 2 MOA initial clinical results reinforce those from two nonclinical studies presented at SITC (Free SITC Whitepaper), which elucidated the effects of trilaciclib on the immune response in human peripheral blood mononuclear cells (PBMCs) and its antitumor efficacy in murine models of breast and colorectal cancer.

Key findings of the in-vitro PBMC study showed that trilaciclib upregulates key processes within the cancer immunity cycle, including:

Trilaciclib increases antigen presentation on tumor cells by upregulating HMC Class I and II, and potentially promotes T cell recruitment to tumor cells by enhancing CXCL10 chemokine production.
Adding trilaciclib to naïve CD8+ T cells enhanced their differentiation into effector memory and central memory T cell populations, irrespective of when trilaciclib was added following T cell activation.
"In these non-clinical studies, trilaciclib favorably alters the tumor microenvironment by promoting the generation of memory T cells," said John Yi, Ph.D., Senior Director, Translational Medicine. "This, in turn, enhances the durability and long-term surveillance of the immune system, so that it can more quickly detect and eradicate tumor cells and limit recurrence. Our data suggest that trilaciclib may induce a feedback loop that promotes antigen presentation and drives recruitment of T cells to tumors."

Key findings in murine syngeneic tumor models of breast and colorectal cancer showed that:

Adding trilaciclib to α-PD-1 and inhibitory receptor immunotherapy (α-TIGIT, α-LAG3, α-CD73) delayed tumor growth and improved survival compared with α-PD-1 and immunotherapy treatment alone.
Adding trilaciclib to α-PD-1 was consistently effective, irrespective of when treatment was initiated, or the tumor model used.
"Trilaciclib has consistently been shown to potentiate combination immunotherapy whether it is with checkpoint blockade therapy or an alternative inhibitory blockade like the adenosine pathway. The broad immune effects of transient G1 arrest represent a novel approach for improving immunotherapies," continued Yi.

Both the clinical and nonclinical data elucidate the immunologic mechanisms underlying the significant survival benefit shown in the previous Phase 2 trial of metastatic triple negative breast cancer patients who received trilaciclib prior to gemcitabine/carboplatin. Additionally, the combined data sets offer proof of principle data that trilaciclib may confer multidimensional clinical benefits across different tumor types and classes of drug.

The SABCS poster, titled, "Trilaciclib Induces Immune Changes Within the tumor Microenvironment in Early-Stage Breast Cancer", and the SITC (Free SITC Whitepaper) posters can be found here.

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 15-20% of such diagnosed breast cancers. TNBC is cancer that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. Because mTNBC cells lack key growth-signaling receptors, patients do not respond well to medications that block estrogen, progesterone, or HER2 receptors. Instead, treating mTNBC 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 mTNBC compared to other forms of breast cancer, and mTNBC 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 December 7, 2022 Ensysce Biosciences, Inc. ("Ensysce" or the "Company") (NASDAQ: ENSC),(OTC PINK: ENSCW), a clinical-stage biotech company applying transformative chemistry to improve prescription drug safety to reduce abuse and overdose, reported that the pricing of an underwritten public offering of 2,900,000 shares of its common stock (or common stock equivalents in lieu thereof) and warrants to purchase up to an aggregate of 5,800,000 shares of common stock at a combined effective public offering price of $1.40 per share of common stock (or pre-funded warrant) and accompanying warrants (Press release, Ensysce Biosciences, DEC 7, 2022, View Source [SID1234624886]). Each warrant is exercisable immediately at an exercise price of $1.40 per share and will expire five years following the date of issuance. The Company expects to receive aggregate gross proceeds of approximately $4.1 million from the offering. The offering is expected to close on or about December 9, 2022, subject to satisfaction of customary closing conditions.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Lake Street Capital Markets, LLC is acting as the sole underwriter for the offering.

The Company has also granted the underwriter a 45-day option to purchase up to an additional 342,000 shares of common stock and/or warrants to purchase up to an additional 870,000 shares of common stock at the public offering price, less the underwriting discounts and commission, to cover over-allotments, if any.

20% of the gross proceeds of the offering will be used to repay a portion of the Company’s outstanding convertible notes. The Company intends to use the remaining net proceeds from the offering for the further clinical development of its product candidates and for working capital and other general corporate purposes.

A registration statement on Form S-1 (File No. 333-268038) relating to these securities was declared effective by the U.S. Securities and Exchange Commission (the "SEC") on December 6, 2022. This offering is being made only by means of a prospectus forming part of the effective registration statement. A preliminary prospectus relating to and describing the terms of the offering has been filed with the SEC. Electronic copies of the preliminary prospectus and, when available, copies of the final prospectus relating to the offering may be obtained for free by visiting the SEC’s website at www.sec.gov or by contacting Lake Street Capital Markets, LLC, Attention: Syndicate Department, 920 Second Avenue South, Suite 700, Minneapolis, Minnesota 55402, or by calling (612) 326-1305, or by emailing [email protected].

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

On December 7, 2022 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated oncology therapeutics, reported that Phase 2 data for CX-2009, a conditionally activated antibody drug conjugate (ADC) targeting CD166, will be presented at the San Antonio Breast Cancer Symposium on December 8th (Press release, CytomX Therapeutics, DEC 7, 2022, View Source [SID1234624885]). The poster details the results from patients treated with monotherapy praluzatamab ravtansine for the treatment of advanced HR+/HER2- breast cancer and triple negative breast cancer (TNBC).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We thank our investigators and the patients and families who contributed to our comprehensive evaluation of praluzatamab ravtansine in breast cancer. Although we elected previously in 2022 not to advance this program further without a partner, this research has benefited many patients, provided important insights into our conditionally activated ADC strategy and informed our next generation of Probody therapeutic candidates," said Sean McCarthy, D.Phil, CEO and Chairman of CytomX.

Details for the poster presentation are as follows:
Presentation Title: Results from a phase 2 study of praluzatamab ravtansine (CX-2009) in patients with advanced breast cancer (ABC)
Poster: P4-01-15
Session and Location: Poster Session 4 – Hall 1
Session Date and Time: December 8, 2022, 7:00 am – 8:15 am CT
Presenting Author: Dr. Kathy Miller, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, USA

On December 7, 2022 Paragon Therapeutics, a biotechnology company dedicated to discovering and developing best-in-class biologics for a range of diseases with high unmet need, reported the launch of Apogee Therapeutics, LLC, its first spinout (Press release, Biosortia Pharmaceuticals, DEC 7, 2022, View Source [SID1234624884]). Apogee is advancing a pipeline of product candidates discovered and developed at Paragon that have potential to reach millions of people living with inflammatory and immunological disorders.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Building on validated protein engineering technologies, Paragon leverages cutting-edge science and technology to rapidly identify and propel biologics from ideation to the clinic. The company’s process combines high-throughput screening systems and optimization techniques to isolate the best possible drug candidates with a CMC model that enables quick and reliable production—aimed at delivering targeted treatment options to patients.

"At Paragon, we are thrilled to announce the launch of Apogee Therapeutics as our first independent company, and we are confident that the Apogee team is well positioned to execute and demonstrate therapeutic leadership in areas of high unmet need," said K. Evan Thompson, Ph.D., Chief Operating Officer of Paragon. "The debut of Apogee validates our approach to advancing best-in-class biologics to patients through a range of opportunities, from new company creation and strategic partnerships to shaping programs in-house with our experienced and proven team."

Apogee was founded in 2022 by Fairmount and Venrock Healthcare Capital Partners and has raised $169 million in financing to date, including an oversubscribed $149 million Series B round co-led by Deep Track Capital and RTW Investments, LP. Under the guidance of CEO Michael Henderson, M.D., the funding is expected to support key leadership, science, and clinical team hires and progress its lead pipeline program, APG777, to the clinic in 2023. As part of its agreement with Paragon, Apogee has an option for exclusive development and commercial rights to a suite of top-tier antibodies specifically engineered to target some of the largest and highest unmet needs in inflammatory and immunological conditions.

"Paragon has mastered the design and development of transformative therapies that meet the highest needs for inflammatory and immune diseases," said Dr. Henderson. "We are excited to build on their work to deliver life-changing therapies that improve patients’ lives."

Paragon was founded in 2021 by Fairmount and is led by a team of innovators with deep expertise in biologics engineering and development. The company’s collaboration with FairJourney Biologics expands its reach and capabilities through dedicated antibody discovery experts and resources. In addition to those partnered with Apogee, Paragon is currently advancing multiple differentiated programs for a range of diseases.