On November 11, 2024 Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company, reported members of the management team are scheduled to participate in a fireside chat at the Stifel 2024 Healthcare Conference, in New York City, on Monday, November 18 th , 2024, at 1:50pm ET (Press release, Geron, NOV 11, 2024, View Source [SID1234648069]).

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!

A webcast of the fireside chat will be available through the Investors and Media section of Geron’s website under Events following the presentation. The webcast will be archived and available for replay for a period of 30 days.

On November 11, 2024 BeyondSpring Inc. (NASDAQ: BYSI) ("BeyondSpring" or the "Company"), a clinical-stage global biopharmaceutical company developing innovative cancer therapies, reported that phase 2 IIT (Investigator-initiated) data on the first 30 patients dosed with plinabulin in the 303 Study of patients with non-small cell lung cancer (NSCLC) after disease progression on PD-1/PD-L1 inhibitors with and without chemotherapy were presented at the 39th Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) Annual Meeting on November 8th, 2024 in Houston, Texas (Press release, BeyondSpring Pharmaceuticals, NOV 11, 2024, View Source;utm_medium=rss&utm_campaign=beyondspring-presents-updated-efficacy-results-from-a-phase-2-iit-study-of-triple-io-combo-of-pembrolizumab-plus-plinabulin-docetaxel-in-metastatic-nsclc-after-progressing-on-prior-immune-checkpoint-i [SID1234648068]).

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!

Docetaxel remains the standard of care for patients with 2L/3L NSCLC without targetable alterations who progress on immune checkpoint inhibitors (ICI) with and without standard chemotherapy. In the recent TROPION Lung-01 phase 3 studies, a similar patient population had an overall response rate (ORR) of 12.8% and median PFS (mPFS) of 3.7 months. In metastatic NSCLC resistant to previous PD-1/L1 therapy1, PD-L1 and CTLA-4 inhibition alone or in combination with hypofractionated radiotherapy produced limited clinical benefits with ~11.5% ORR.

This investigator-initiated, single-arm, open-label, phase 2 study (KeyPelms-004 or 303 Study) evaluates the efficacy and safety of a triple combination regimen of pembrolizumab plus plinabulin/docetaxel (NCT05599789). The study intends to enroll a total of 47 patients and is ongoing at Peking Union Medical College Hospital, Beijing, China with the principal investigator Dr. Mengzhao Wang, Chief of the Department of Respiratory and Critical Care Medicine. Here, we report on updated results from 30 patients.

At the database lock on 29 August 2024, 36 patients were enrolled, 30 exposed to the plinabulin regimen. Prior to entry, all patients had experienced disease progression after initial clinical benefit with ICI. Of the 30 treated patients (median age at 68.0 years; ranged 50-77 years), 73.3% were male and 26.7% were female; 60% were current or former smokers. Histology included 57% patients (n=17) with non-squamous cell carcinoma and 43% (n=13) with squamous cell carcinoma. The median follow-up was 11.5 months. Below is an efficacy summary table:

Primary Endpoint Plinabulin + Pembrolizumab + Docetaxel (n=30)
Confirmed ORR (RECIST 1.1) 21.1%
Secondary Endpoints
Median PFS (RECIST 1.1) 8.6 M
Median OS
(Overall Survival)

Not reached
Median DoR
(Duration of Response)

11.4 M
Disease Control Rate
(PR + SD > 4 months)

89.3%
(25/28 – 2 patients withdrew after first dose)

The combination was generally well tolerated. 46.7% of patients experienced grade 3 or higher treatment-related adverse effects. Most common AE is myelosuppression (13.3%), GI side effect (13.3%), and transient hypertension (6.7%). There were no treatment-related deaths.
Results are consistent with the data reported on the first 19 patients in Study 303 at ESMO (Free ESMO Whitepaper) in September
"Plinabulin is a potent inducer of dendritic cell or DC maturation that leads to T cell activation. DCs are the most potent antigen presenting cell (APC). This unique mechanism of action reinforces anti-tumor immune response with the potential to overcome acquired ICI resistance, which may derive from APC pathway alteration or T cell exhaustion. Compared to historical controls of 3-4 months of median PFS2, the efficacy data with 30 patients maintained a doubled median PFS at 8.6 months, coupled with an impressive disease control rate of almost 90%, which continues to be encouraging and clinically meaningful for this severe unmet need," said Dr. Mengzhao Wang, principal investigator at Peking Union Medical College Hospital.

SITC 2024 Abstract Title: Phase 2 Study of Pembrolizumab (pemb) plus Plinabulin (plin) and Docetaxel (doc) for Metastatic NSCLC after Failure on First-line Immune Checkpoint Inhibitor Alone or Combination Therapy: Updated Efficacy and Safety Results on Immune Re-sensitization

Presenting Author: Yan Xu, Peking Union Medical College Hospital
Abstract Number: 1491

References:

Schoenfeld et al. 2022, Lancet Oncology 23:279-291
Ahn et al. 2024, TROPION Lung-01 Study, Journal of Clinical Oncology, View Source
About Plinabulin

Plinabulin is a novel first-in-class dendritic cell maturation therapeutic with durable anti-cancer benefit observed across multiple clinical studies. As a reversible binder at a distinct tubulin pocket, plinabulin does not change tubulin dynamics or antagonize tubulin stabilizing agents, such as docetaxel, which contributes to its differentiated activity and tolerability compared to other tubulin binders. In addition, plinabulin significantly reduces chemotherapy induced neutropenia and could thereby increase docetaxel tolerability. Around 800 patients have been treated with plinabulin with good tolerability.

About 303 Study

303 Study is an open-label, single-arm Phase 2 Study of Plinabulin plus docetaxel and pembrolizumab for previously treated patients with metastatic NSCLC and progressive disease after anti-PD-(L)1 inhibitor alone or in combination with platinum-doublet chemotherapy. This study evaluates the efficacy and safety of this triple combination and is being conducted at Peking Union Medical College Hospital, Beijing, China. The regimen includes Pembrolizumab 200 mg IV every 3 weeks (Q3W) on Day 1, Docetaxel 75 mg/m2 IV Q3W on Day 1 and Plinabulin 30mg/m2 IV Q3W on Day 1 in a 21-day cycle. The primary endpoint is investigator-based ORR (RECIST 1.1). The secondary endpoints include PFS, OS, DoR, and safety. The study intends to enroll 47 patients. The study is funded by Merck’s Investigator Studies Program with provision of study drug and financial support.

On November 11, 2024 Alligator Bioscience AB ("Alligator") (ATORX) and Aptevo Therapeutics ("Aptevo") (Nasdaq: APVO) reported preliminary data from the companies’ Phase 1 trial evaluating the first-in-class bispecific antibody, ALG.APV-527, as monotherapy for the treatment of multiple solid tumor types likely to express tumor antigen 5T4 (Press release, Alligator Bioscience, NOV 11, 2024, View Source [SID1234648067]). These data indicate that trial endpoints of adequate exposure, safety, tolerability and biological activity were met. Outcomes were presented at a poster session on Friday, November 8, 2024, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference in Houston, Texas.

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 interim results from Phase 1 trials of ALG.APV-527 are showing encouraging outcomes, particularly in terms of safety and disease stability in the trial patients who were refractory to multiple previous therapies. Among evaluable patients, 56% (9/16) achieved stable disease in this monotherapy trial. A colon cancer patient remained on study with stable disease for more than six months as well as a breast cancer patient who remained stable for over 11 months. Importantly, there were no instances of serious liver toxicity, a notable outcome given the relatively high incidence of this side effect associated with other treatments targeting 4-1BB. By leveraging a novel bispecific approach, ALG.APV-527 aims to enhance anti-tumor immunity while avoiding the systemic toxicities that previously have hampered the 4-1BB immune receptor pathway. These findings underscore the drug’s potential as a viable option for patients with solid tumors," noted Dr. Thomas Marron, MD, PhD, Professor of Immunology & Immunotherapy and Hematology/Oncology at the Icahn School of Medicine at Mount Sinai, and a leading investigator in the trial.
Clinical Highlights
Safety and Tolerability

ALG.APV-527 demonstrated positive safety and tolerability across all cohorts
No serious liver toxicity, a common side effect of other 4-1BB targeting treatments that can cause patients to discontinue dosing, was observed
A maximum tolerated dose has not been identified, highlighting the tolerability of the drug at high dose levels
Clinical Activity/Efficacy

Nine of 16 efficacy evaluable patients (56%) achieved stable disease (SD)
One colon cancer patient achieved SD for more than six months
The longest SD duration was in a breast cancer patient who entered the study with progressive disease, achieved stable disease and remained on study for >11 months. This patient successfully transitioned to a higher dose level twice
Evidence of biological activity of ALG.APV-527

ALG.APV-527 could be measured in all patients. Serum concentrations of ALG.APV-527 were proportional to the administered dose
Analysis of biomarkers in the serum of treated patients including soluble 4-1BB (surface protein found on certain immune cells) confirm biological activity of ALG.APV-527
Analysis of biomarkers in biopsies (including the 5T4 target cells and CD8 T cancer killer cells are consistent with immune activation in the tumor microenvironment). This observation consistent with ALG.APV-527 expected MOA.
About the Trial
The ALG.APV-527 Phase 1 trial is a multi-center, multi-cohort, open-label dose-escalation trial that includes administration of ALG.APV-527 in up to six escalating dose levels in a 3+3 design*. The trial is enrolling adult patients with multiple solid tumor types/histologies likely to express the 5T4 antigen. ALG.APV-527 will be given intravenously once every two weeks. The trial is assessing the safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of ALG.APV-527.

*The 3+3 design proceeds in cohorts of three patients treated at increasing dose levels. Dose escalation stops when at least two out of three or six patients experience dose limiting toxicities (DLTs) at that dose level.

About ALG.APV-527
ALG.APV-527 is a bispecific conditional 4-1BB agonist, only active upon simultaneous binding to 4-1BB and 5T4. This has the potential to be clinically important because 4-1BB can stimulate the immune cells (antitumor-specific T cells and NK cells) involved in tumor control, making 4-1BB a particularly compelling target for cancer immunotherapy. 5T4 is an oncofetal tumor associated antigen overexpressed on numerous solid tumors including non-small-cell lung carcinoma (NSCLC), breast, head and neck, cervical, renal, gastric, and colorectal cancer.

Preclinical studies, highlighting the differentiated design of the molecule that minimizes systemic immune activation, allowing for highly efficacious tumor-specific responses as demonstrated by potent activity in preclinical models, has been published in the peer-reviewed publication, Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

On November 11, 2024 Abcuro, Inc., a clinical-stage biotechnology company developing therapies for the treatment of autoimmune diseases and cancer through precise modulation of cytotoxic T cells, reported that Alex Martin, Chief Executive Officer, will present at the following investor conferences (Press release, Abcuro, NOV 11, 2024, View Source [SID1234648065]).

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!

Stifel 2024 Healthcare Conference: Presentation on November 18, 2024, at 3:00 pm E.T.
Piper Sandler 36th Annual Healthcare Conference: Presentation on December 3, 2024, at 4:10 pm E.T.

On November 11, 2024 Imugene Limited (ASX: IMU), a clinical stage immuno-oncology company, reported the dosing of the first patient in the intratumoural (IT) combination arm of its Phase 1 onCARlytics (CF33-CD19) clinical trial (Press release, Imugene, NOV 11, 2024, https://mcusercontent.com/e38c43331936a9627acb6427c/files/0b72d5aa-3410-e210-9537-71ef3b912378/onCARlytics_Trial_Doses_First_Patient_in_IT_Combination_Arm.pdf [SID1234648060]). This development is part of the OASIS trial, which is designed to assess the safety and efficacy of Imugene’s CD19 oncolytic virotherapy in patients with advanced or metastatic solid tumours.

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 OASIS trial is a Phase 1 dose escalation study that explores two routes of administration, intratumoural (IT) injection and intravenous (IV) infusion. onCARlytics, a CD19-expressing oncolytic virus, is being investigated both as a monotherapy and in combination with the CD19-targeting bispecific antibody blinatumomab, an established cancer immunotherapy.

Imugene Managing Director & CEO Leslie Chong said: "We are pleased to have dosed the first patient in the intratumoural arm of our OASIS trial. With CD19 being a well-established target in blood cancers, we are optimistic about the effectiveness it could show in solid tumours. onCARlytics has the potential to induce expression of CD19 on the surface of solid tumours and allowing existing CD19 therapies to recognise and attack the cancer. We’re pleased to continue advancing this prospective new treatment option for those in need."

OASIS is currently being conducted at seven sites in the U.S. including City of Hope, University of Cincinnati, and MD Anderson Cancer Center, with the potential to open a total of 10 sites to recruit up to approximately 40 patients with advanced solid cancers that have spread. The primary objective of the trial is to evaluate the safety and efficacy of onCARlytics, either by IT injection or IV infusion, either alone, or in combination with blinatumomab. In February, the first patient with bile tract cancer was dosed in the IV monotherapy arm of the trial at City of Hope in California. Subject to the rate of patient enrolment, preliminary IT and/or IV combination status is expected in the fourth quarter of 2024.

The trial is titled: "A Phase I, Dose Escalation and Dose Expansion, Safety and Tolerability Study of onCARlytics (CF33-CD19), Administered Intravenously or Intratumorally in Combination with Blinatumomab in Adults with Advanced or Metastatic Solid Tumors." See View Source