1stOncology™: Cancer Intelligence Service – Page 5660 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

G1 Therapeutics Announces Investigator Initiated Study of Trilaciclib and Lurbinectedin in Patients with Extensive Stage Small Cell Lung Cancer

On October 26, 2022 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that it is supporting a Phase 2 investigator initiated study (ISS) of trilaciclib and lurbinectedin in patients with extensive stage small cell lung cancer (ES-SCLC) (Press release, G1 Therapeutics, OCT 26, 2022, View Source [SID1234622389]). An ISS is a study that is proposed, developed, and conducted by a qualified sponsor external to G1 Therapeutics who assumes full responsibility for the conduct of the study.

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!

Trilaciclib, an IV-administered transient CDK4/6 inhibitor, is a first-in-class therapy designed to preserve bone marrow and immune system function during chemotherapy to improve patient outcomes.

"Pretreatment with trilaciclib may improve the therapeutic potential of lurbinectedin, another important medication for SCLC, in multiple ways," said Jared Weiss, M.D., Professor of Medicine, Division of Oncology, Lineberger Comprehensive Cancer Center at the University of North Carolina Chapel Hill, NC and principal investigator in this study. "Trilaciclib is a proven myeloprotective agent, but studies to date have only assessed it in the context of topotecan-containing and platinum/etoposide-containing chemotherapeutic regimens. Lurbinectedin is effective, but also highly myelosuppressive, which is particularly problematic given recent data that clarify the importance of maintaining adequate exposure for efficacy. The opportunity for immunological synergy with lurbinectedin – which potently suppresses myeloid derived suppressor cells (MDSCs) – is also evident given data that suggest trilaciclib’s ability to induce novel T cell clonality, improve the CD8+ T cell/Treg ratio, and increase antigen expression and presentation."

This is a prospective, non-randomized, single-arm Phase 2 study, to evaluate trilaciclib administered intravenously prior to lurbinectedin in approximately 30 subjects with platinum refractory ES-SCLC. Patients will receive trilaciclib and lurbinectedin on day one of each 21-day cycle until discontinuation or disease progression.

The primary endpoint is the rate of grade 4 neutropenia in any cycle when trilaciclib is administered prior to lurbinectedin in subjects with extensive stage small cell lung cancer (ES-SCLC). Secondary endpoints include mean duration (days) of grade 4 neutropenia in cycle 1, overall survival (OS), progression-free survival (PFS), overall rate of response (ORR), quality of life assessments, and the use of secondary/reactive supportive measures including G-CSF administration.

About Small Cell Lung Cancer
In the United States, about 29,000 cases of small cell lung cancer (SCLC) are diagnosed each year. SCLC, one of the two main types of lung cancer, accounts for about 10% to 15% of all lung cancers. SCLC is an aggressive disease and tends to grow and spread faster than NSCLC. It is usually asymptomatic; once symptoms do appear, it often indicates that the cancer has spread to other parts of the body. About 70% of people with SCLC will have cancer that has metastasized at the time they are diagnosed. The severity of symptoms usually increases with increased cancer growth and spread. From the time of diagnosis, the general 5-year survival rate for people with SCLC is 6%. The five-year survival rates for limited-stage (the cancer is confined to one side of the chest) SCLC is 12% to 15%, and for extensive stage (cancer has spread to the other lung and beyond), survival rates are less than 2%. Chemotherapy is the most common treatment for SCLC.

Orionis Biosciences Demonstrates Platform Capabilities of Genome-scale Molecular Glue Discovery and Rational Design at Targeted Protein Degradation Summit

On October 26, 2022 Orionis Biosciences, a life sciences company pioneering innovation of highly selective and tunable therapeutics for cancer and beyond, reported that it will present preclinical data supporting its Allo-GlueTM protein degradation platform for discovery and rational design of small molecule molecular glues at the 5th Annual Targeted Protein Degradation Summit, taking place October 25 – 28 in Boston (Press release, Orionis Biosciences, OCT 26, 2022, View Source [SID1234622388]). The data include platform achievements for ligase-centric and target-centric discovery of molecular glue compounds with potential to modulate previously intractable disease targets.

"Molecular glues have the potential to greatly extend the treatment of challenging diseases like cancer, and there is vast untapped power in this modality. A lack of systematic, scalable discovery and design approaches to molecular glues has, however, limited the field," said Riccardo Sabatini, Ph.D., Chief Data Scientist at Orionis. "Today we are presenting new data that demonstrate the ability of Orionis’ proprietary Allo-GlueTM platform to transform glue discovery into a genome-scale, high throughput and rational discovery paradigm. Our large-scale interrogation of small molecule-triggered protein-protein interactions makes it abundantly clear that molecular glue mechanisms are more common than previously appreciated. Clearly, this presents a large and exciting space for chemistry innovation."

The Allo-Glue platform can interrogate more than 18,000 target proteins simultaneously — virtually the entire human proteome — as well as diverse and privileged chemical libraries, at scale and in an unprecedented, unbiased manner across large number of targets and target classes, including traditionally intractable disease targets. To date, Orionis has mapped more than 150 million molecular glue interactions. This growing data set will provide the company with unique opportunities to further evolve and apply its novel numerical modelling approaches to the rational design of molecular glues.

To date, Orionis’ Allo-Glue platform has:

Identified multiple monovalent glues and targets for new ligases beyond the E3 ligase cereblon: A series of molecules have demonstrated strong and highly selective target recruitment and degradation in preclinical studies, further validating the concept that drug-induced, selective degradation of proteins is achievable with multiple types of E3 ligases and targets
Established the feasibility of target-centric approaches to glue discovery, as exemplified by discovery of drug-like molecules for traditionally intractable oncology targets
Evolved and applied computational methods and machine learning models to rational expansion and design of new molecular glues
Details of today’s presentation are as follows:

5th Annual Targeted Protein Degradation, October 25-28, 2022, Boston, Massachusetts

Title: Monovalent Molecular Glues: Cereblon and Beyond
Date and Time: Wednesday, October 26, 5:00 p.m. ET
Presenter: Riccardo Sabatini, Chief Data Scientist, Orionis Bio
Last week Orionis announced a $55 million financing to support entry of its lead cancer immunotherapy programs into the clinic. In addition to its Allo-Glue molecules, Orionis is rapidly advancing a deep pipeline of biologics for the treatment of cancer based on its A-KineTM platform, which engineers target-selective, conditionally active cytokines designed to trigger anti-tumor immune responses even in cold tumors that lack prevalent immune involvement and are refractory to checkpoint inhibitor therapies. A-Kines aim to avoid the systemic toxicities observed with traditional cytokine therapies. The company anticipates IND submission and start of a Phase 1 study of a conditionally active cytokine, driven by its proprietary A-Kine platform, in 2023.

"We are all very excited about the continued progress the company is making with its multipronged technology and therapeutic approaches to currently hard to treat cancers. Our R&D engine has the potential to address some of the biggest challenges in drug discovery, including diseases beyond cancer," said Nikolai Kley, co-founder, President and Chief Executive Officer of Orionis Biosciences.

Propanc Biopharma’s CEO to Present at Sidoti & Company Micro-Cap Virtual Investor Conference

On October 26, 2022 Propanc Biopharma, Inc. (OTC Pink: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, reported that Mr. James Nathanielsz, Propanc’s Chief Executive Officer and Co-Founder, will conduct investor meetings and present at the upcoming Sidoti & Company’s upcoming Micro-Cap Virtual Investor Conference, which will be held on Wednesday and Thursday, November 9 – 10, 2022 (Press release, Propanc, OCT 26, 2022, View Source [SID1234622387]).

Mr. Nathanielsz will deliver his corporate presentation on Wednesday, November 9, at 4:00pm, Eastern Standard Time.

The Sidoti & Company Micro-Cap Investor Conference is a virtual event featuring dynamic, micro-cap companies interacting with a number of institutional investors from across the United States. Sidoti & Company is a provider of independent securities research focused on small and micro-cap companies and the institutions that invest in their securities. Their investor conferences have emerged as a leading forum for interaction between issuers and investors in the small and micro-cap investment community.

"The demand for innovative healthcare companies by institutional investors to present at the upcoming Sidoti & Company Micro-Cap Conference led to an exciting opportunity for Propanc to present the latest developments of our lead product candidate, PRP, as we advance towards a First-In-Human study in advanced cancer patients suffering from solid tumors," said Mr. Nathanielsz. "I look forward to demonstrating how PRP treats and prevents metastatic cancer by targeting and eradicating cancer stem cells, free from side effects associated with standard treatment approaches. Furthermore, we recently announced potential future clinical applications in conjunction with our joint research partners, where PRP alters the tumor microenvironment. This means pre-treating tumors which are chemo-resistant so that they are susceptible to standard therapies once again."

PRP is a mixture of two proenzymes, trypsinogen and chymotrypsinogen from bovine pancreas administered by intravenous injection. A synergistic ratio of 1:6 inhibits growth of most tumor cells. Examples include kidney, ovarian, breast, brain, prostate, colorectal, lung, liver, uterine and skin cancers.

Alpine Immune Sciences Terminates Oncology Trials after Second Patient Death

On October 25, 2022 Alpine Immune Sciences reported the company has terminated two clinical trials for its anti-cancer candidate davoceticept after a second patient death attributed to cardiogenic shock. Davoceticept (ALPN-202) is a CD28 costimulator and dual checkpoint inhibitor immunotherapy that was been tested in concurrent clinical trials: NEON-1 with the candidate being evaluated as a monotherapy; and NEON-2 a study of a combination therapy of davoceticept and pembrolizumab (KEYTRUDA).

Both studies were voluntarily terminated by Alpine, though the two patient deaths occurred in the NEON-2 combination therapy trial. The second patient with metastatic colorectal cancer had been treated previously with a colectomy and other chemotherapeutic agents, and died after the administration of a single dose of davoceticept and pembrolizumab.

NEON-2 had previously been placed on a partial clinical hold in March—which allows a company to continue running a trial, but bars it from recruiting new patients—after the first reported death in the trial. At the time, the NEON-1 trial of davoceticept was unaffected, but after this second death, Alpine decided to shutter both studies.

"Patient safety remains our highest priority," said Mitchell H. Gold, MD, executive chairman and CEO of Alpine in a press release. "We have determined it is in the best interest of all patients to terminate enrollment in the davoceticept studies and we will continue to work with the U.S. Food and Drug Administration, Merck, the study Safety Monitoring Committee, and the study investigators to further understand this important safety issue. Davoceticept has shown encouraging signs of clinical activity and it is unfortunate we have not yet been able to identify a safe dose regimen for the combination with pembrolizumab."

The company now will turn its attention to advancing its lead program ALPN-303, a dual B cell cytokine (BAFF/APRIL) antagonist, which has shown potential against multiple autoimmune and inflammatory indications. In September, the company reported data from it Phase 1 RUBY study of ALPN-303 in healthy volunteers and non-clinical studies.

The RUBY study showed the candidate was well tolerated in both intravenous or subcutaneous at doses up to 960 mg. It also showed improved potency against BAFF and APRIL, and demonstrated superiority against BAFF- or APRIL-only inhibitors, as well as wild-type TACI, in preclinical disease models.

"The initial healthy volunteer data with ALPN-303 suggest a differentiated and potentially best-in-class development profile, which we anticipate could have a meaningful impact on clinical outcomes in SLE (systemic lupus erythematosus) and also potentially a wide range of autoantibody-related inflammatory diseases," noted Stanford Peng, MD, PhD, Alpine’s president and head of R&D, in a statement released at the company’s RD day.

Based on this, the company now plans a Phase II randomized, placebo-controlled proof-of-concept study in SLE as well as open-label basket studies in renal, hematologic, and dermatologic autoimmune diseases, which it expects to initiate in late 2023.

In addition to ALPN-303, Alpine also has a collaboration with AbbVie for acazicolcept in SLE and has additional preclinical and clinical collaborations with Horizon Discovery and Adaptimmune.

(Press release, Alpine Immune Sciences, OCT 25, 2022, View Source [SID1234661011])

GT Biopharma Presents at LD Micro on October 26, 2022 at 4:30 pm PST

On October 25, 2022 GT Biopharma, Inc. (NASDAQ: GTBP) (the "Company" or "GTB"), a clinical stage immuno-oncology company focused on developing innovative therapeutics based on the Company’s proprietary natural killer (NK) cell engager, TriKE platform, reported that the Interim Chief Executive Officer and Executive Chairman, Michael Breen, will present a corporate overview to investors at the LD Micro Main Event XV taking place October 25-27, 2022, at the Luxe Sunset Boulevard Hotel in Los Angeles (Press release, GT Biopharma, OCT 25, 2022, View Source [SID1234623367]).

To access the live webcast of the company’s presentation on October 26th at 4:30 p.m. PDT, please visit View Source to access the "Track 2" presentation.