On June 6, 2023 ISA reported the first clinical data of the combination of ISA101b (peltopepimut-S) and Regeneron’s anti-PD-1 Libtayo (cemiplimab) at the ASCO (Free ASCO Whitepaper) annual meeting in Chicago (Press release, ISA Pharmaceuticals, JUN 6, 2023, View Source [SID1234632516]).

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Dr. Kong presented data regarding 26 patients with recurrent and/or metastatic Human Papilloma Virus type 16 (HPV16) positive oropharyngeal cancer (OPC, a form of head and neck cancer) who progressed on pembrolizumab or nivolumab, and were followed for at least 6 months. This population included patients that have never responded to prior anti-PD1 therapy. Patients were treated until disease progression, toxicity, treatment withdrawal or up to 24 months. Recruitment in this study is ongoing. Further information can be found on clinicaltrials.gov (NCT04398524).

The combination of ISA101b and cemiplimab in these patients resulted in an overall response rate (ORR) of 15.4%, as per investigator assessment. Long term (≥6 months) disease stabilization was achieved in 26.9% of all patients. The combination of cemiplimab and ISA101b was generally well tolerated with a safety profile resembling that of anti-PD-1 monotherapy. There were two grade 3 adverse events related to ISA101b. Grade 4-5 events related to study treatment did not occur. Re-ignition of an anti-tumor effect of anti-PD-1 therapy after failure of checkpoint inhibition by the addition of a therapeutic vaccine is a unique feature.

Dr. Anthony Kong, Principal Investigator and Medical Oncologist at King’s College in London, said: "The initial results of this study are promising, given the high unmet medical need in this difficult-to-treat patient population."

Leon Hooftman, Chief Medical Officer of ISA Pharmaceuticals, said: "The most impressive element of this data-set of anti-PD1 therapy-resistant head and neck cancer patients is the 6 months’ Disease Control Rate’ (DCR): it appears that the targeted therapeutic cancer vaccine ISA101b together with an anti-PD1 antibody can have a real stabilizing effect in a fair proportion of these sick patients."

Head-and-neck cancer can be a severe and life-threatening disease. HPV16 is a major cause of head-and-neck cancer. Recurrent and metastatic HPV16 positive OPC is a form of head-and-neck cancer with a high unmet medical need. In September 2021 the FDA granted Fast Track designation to ISA101b for the treatment of recurrent and metastatic HPV16 positive OPC.

For more information, please contact us at [email protected].

On June 6, 2023 Intensity Therapeutics, Inc. ("Intensity"), a clinical-stage biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral (IT) cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported that data from its INVINCIBLE study was presented on June 4, at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago and virtually from June 2-6, 2023 (Press release, Intensity Therapeutics, JUN 6, 2023, View Source [SID1234632515]).

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The INVINCIBLE study is a phase 2, randomized, open label, multi-center study that enrolled 91 women with newly diagnosed operable early-stage intermediate or high-grade T1-T2 invasive breast cancers who were randomly allocated (2:1) prior to resection to IT injections of INT230-6, no treatment or saline sham injection. The study is evaluating clinical and biological effects in patients with early-stage operable breast cancer. The study presented new immune and gene activation related results as well as data demonstrating efficacy and tolerability of INT230-6.

Abstract Title: A phase 2 randomized window of opportunity trial evaluating cytotoxic and immunomodulatory effects of intratumoral INT230-6 in early stage breast cancer: The INVINCIBLE Trial.
First Author: Angel Arnaout, MD, FACS
Session Type/Title: Poster Session/Breast Cancer—Local/Regional/Adjuvant
Session Date and Time: Sunday, June 4, 2023, 9:00 AM – 12:00 PM EDT
Location: In-Person & On Demand
Abstract Number: 573
Poster: 403
Copies of the presentation materials are available on Intensity’s website on the publications, papers and posters page.

"For the majority of breast cancer patients, the typical waiting period of 2-6 weeks from diagnosis to surgery is a very fearful time. Surgeons and patients feel powerless, as there are currently no therapeutic options for the patient prior to the surgery," said Angel Arnaout, M.D., Scientist and Surgical Oncologist at the Ottawa Hospital, and Professor of Surgery at the University of Ottawa and Co-lead of the Ontario Institute for Cancer Research (OICR) WOO Network. "We have previously reported that the active drug agents comprising INT230-6 cause tumor cell death and high levels of necrosis in multiple breast cancer subtypes including triple negative breast cancer following direct intratumoral injection. The ability, with just one or two doses of this agent, to elicit a rapid and marked cytotoxic and immune induction response within the tumor during the surgical waiting period, all without an increase in postoperative complications, is very novel and highly attractive to patients. For the first time, there is the possibility that patients will have a treatment that can ignite the immune system prior to lumpectomy or mastectomy that may protect the patient from disease recurrence. We look forward to future studies to demonstrate that INT230-6 intratumoral injections can create a positive, long term clinical benefit for patients with breast cancer. As a surgeon, I am excited about how this new drug may shift the way we treat all cancer patients awaiting surgery, in general."

"From Part 2 of our study, we saw an increase in expression levels of dendritic cells, macrophages and CD4 T cells, post treatment, when comparing patients treated with drug with the control group," said Dr. Melanie Spears, Co-Director of Diagnostic Development, OICR and Co-lead of the WOO Network. "The cell death activates an anti-cancer immune response as evidenced by relative increase in the abundance of CD4 T naïve, B and NK cells, post treatment when comparing treated patients with the control group. Further work is currently in process to determine whether a global immune activation has occurred."

"INT230-6 has novel mechanism of action and is a potential, new weapon in the war on cancer. This drug can cause extensive necrosis with favorable clinical results as a monotherapy in presurgical and metastatic patients with advanced, relapsed and refractory disease," stated Lewis H. Bender, President and Chief Executive Officer of Intensity. "These new results reported from the INVINCIBLE breast cancer study provide further evidence and support for the potential of our drug in treating local disease prior to surgery. Specifically, the data from Part 2 of the INVINCIBLE study show that INT230-6 elicits both rapid direct tumor killing and immune activating effects. Having completed enrollment, we look forward to concluding the analysis and reporting the full patient study results in the future."

About INT230-6

INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is composed of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule (SHAO) that helps disperse the potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor resulting in a favorable safety profile. In addition to local disease control, direct killing of the tumor by INT230-6 releases a bolus of neoantigens specific to the patient’s malignancy, leading to engagement of the immune system and systemic anti-tumor effects. Importantly, these effects are mediated without the immunosuppression of concomitant systemic chemotherapy.

About the INVINCIBLE Study

The INVINCIBLE study is a phase 2, randomized, open label, multi-center study, that enrolled 91 women with newly diagnosed operable early-stage intermediate or high-grade T1-T2 invasive breast cancers who were randomly allocated (2:1) prior to resection to IT injections of INT230-6, no treatment or saline sham injection. The study had two parts. Part 1 (N=29) randomized patients 2:1 to either 1-3 doses of INT230-6 injected weekly or no treatment, 2 to 5 weeks prior to surgery (lumpectomy or mastectomy). The purpose of this portion of the trial was to evaluate safety, feasibility, and optimal drug dosing. Part 2, now complete, was a double-blind, randomized arm of 62 patients, where patients were randomized 2:1 to receive one or two IT doses of INT230-6 vs. saline injection. The objective of using saline was to rule out the potential confounding effect of hydrostatic pressure on tumor necrosis. The results of Part 2 further evaluated the potential cytotoxic, immunomodulatory and other biologic effects of INT230-6 and its role as a potential cancer therapy in breast cancer patients awaiting surgery. The INVINCIBLE Study is being conducted under a Health Canada (HC) approved Clinical Trial Application (CTA), under the direction and supervision of Principal Investigator, Dr. Angel Arnaout. The Ottawa Hospital Research Institute (OHRI) conducted subject enrollment and treatment, and evaluated pathological and clinical responses. OICR will analyze subject immune responses and conduct biomarker analyses.

About Potential INT230-6 Approval Pathways in the Presurgical Setting

The U.S Food and Drug Administration (FDA) instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint. Pathological complete response (pCR) is an accepted FDA accelerated approval criterion for approval in high-risk breast cancer, such as TNBC subtype. Pathological complete response is defined as the absence of residual invasive and in situ cancer after evaluation of the complete resected breast specimen and lymph nodes following completion of neoadjuvant systemic therapy.

Data from the INVINCIBLE study has provided an understanding of the effect of INT230-6 on cancer cell proliferation and tumor necrosis. INT230-6 causes increased tumor necrosis with good safety, and the addition of INT230-6 to the existing or a modified neoadjuvant (presurgical) systemic standard-of-care treatment regimen may increase pCR rates in TNBC or HER+ patients. In November of 2020, Intensity Therapeutics met with FDA and discussed the potential use of INT230-6 in the presurgical neoadjuvant breast cancer setting in an accelerated approval program. A new meeting with the FDA is being planned.

On June 6, 2023 iBio, Inc. (NYSEA:IBIO) ("iBio" or the "Company") reported the expansion of its AI-powered technology stack with the launch of EngageTx, a proprietary T-cell engager antibody panel designed for developing bispecific antibodies for immuno-oncology applications (Press release, iBioPharma, JUN 6, 2023, View Source [SID1234632513]). Through comprehensive screening and optimization techniques, iBio has identified highly potent, fully human TROP-2 (Trophoblast Cell Surface Antigen 2) monoclonal antibodies, which have been formatted into bispecific TROP-2 x CD3 molecules using EngageTx.

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EngageTx comprises a robust array of CD3-binding antibodies, designed to be paired with tumor-targeting antibodies, such as TROP-2. This combination yielded a potent bispecific molecule that effectively mobilizes T-cells to unleash their anti-cancer capabilities against malignant cells. While iBio discovered the panel earlier this year, the Company is now deploying it internally, as well as offering it for use in potential future commercial partnerships.

"By strategically employing bispecific antibodies targeting TROP-2, we aim to stimulate the immune system for treating TROP-2-positive cancers, offering potential advantages over existing therapies," said iBio’s Interim Chief Executive Officer and Chief Scientific Officer, Martin Brenner, DVM, Ph.D. "The generation of a highly potent TROP-2 bispecific with reduced cytokine release offers validation of our technology and its differentiated capabilities. We look forward to harnessing EngageTx to enrich our pipeline and offering this tremendous potential resource to prospective partners."

TROP-2 is highly expressed in multiple solid tumors, including breast, lung, colorectal, and pancreatic cancers and is closely linked to metastasis and tumor growth. TROP-2 antibody drug conjugates have been developed to deliver toxic payloads to these cancer cells but could risk harming healthy cells and cause adverse effects. The Company’s bispecific approach has the potential to increase the therapeutic window, while promoting a robust and long-lasting anti-tumor response. Combining the bispecific TROP-2 approach with immunotherapies like checkpoint inhibitors can potentially lead to improved clinical outcomes.

"Developing bispecifics is notoriously challenging," said Matt Greving, Ph.D., VP & Head of Machine Learning & Platform Technologies at iBio. "EngageTx is an important addition to iBio’s tech stack and demonstrates the power of our patented, AI-guided epitope engineering and StableHu antibody optimizer technologies, which were used to build EngageTx."

Features of the EngageTx panel include:

Broad range of T-cell activity for optimized pairing with diverse tumor antigen arms;
Reduced cytokine release for potentially expanded therapeutic window; and
Human-primate cross reactivity to facilitate molecule de-risking in safety studies.

On June 6, 2023 GSK plc (LSE/NYSE: GSK) reported the US Food and Drug Administration (FDA) accepted the supplemental Biologics License Application (sBLA) for Jemperli (dostarlimab) in combination with chemotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer (Press release, GlaxoSmithKline, JUN 6, 2023, View Source [SID1234632512]). If approved in this patient population, dostarlimab plus chemotherapy could represent the first meaningful frontline treatment advancement in decades for patients with primary advanced or recurrent endometrial cancer.

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The FDA granted Priority Review for this application and assigned a Prescription Drug User Fee Act action date of 23 September 2023. Dostarlimab also was recently granted Breakthrough Therapy designation for this potential new indication.

Under Project Orbis, an initiative from the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology products among international partners, the dostarlimab sBLA will be reviewed by health authorities in the US, Australia, Canada, Switzerland, Singapore and the United Kingdom.

Hesham Abdullah, Senior Vice President, Global Head of Oncology Development, GSK said: "We are excited about this initial filing for this potential new indication for dostarlimab in the patient population that demonstrated the strongest treatment effect in the phase III RUBY trial. Long-term outcomes for patients with primary advanced or recurrent endometrial cancer remain poor, and there is an urgent need to evolve the current standard of care, which is platinum-based chemotherapy. We look forward to working with the FDA and other health authorities as they review this application."

Endometrial cancer is the most common gynaecologic cancer in developed countries,[1] and there are about 60,000 new cases of endometrial cancer diagnosed every year in the US.[2] Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.[3][4] An estimated 20-29% of all endometrial cancers are dMMR/MSI-H.[5] Chemotherapy used alone is the current standard of care for primary advanced or recurrent endometrial cancer, and many patients eventually experience disease progression.[6]

Currently, in endometrial cancer, dostarlimab is approved in the US as monotherapy in dMMR recurrent or advanced endometrial cancer that has progressed on or following a prior platinum-containing regimen. If the sBLA is approved, dostarlimab could potentially be indicated earlier in treatment in combination with platinum-containing chemotherapy for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer.

The sBLA is based on the prespecified interim analysis results from Part 1 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial. The trial met its primary endpoint of investigator-assessed progression-free survival (PFS), which demonstrated a statistically significant and clinically meaningful benefit in patients treated with dostarlimab plus carboplatin-paclitaxel in the dMMR/MSI-H population and in the overall population. The data reflect a robust median duration of follow-up of ≥24.8 months. The safety and tolerability analysis from RUBY showed a safety profile for dostarlimab and carboplatin-paclitaxel that was generally consistent with the known safety profiles of the individual agents. These data were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Plenary and the Society of Gynecologic Oncology (SGO) Annual Meeting on 27 March 2023, and were simultaneously published in The New England Journal of Medicine.

Part 1 of the RUBY trial continues to assess the dual-primary endpoint of overall survival (OS) in the intent-to-treat (ITT) population. At the first interim analysis in the ITT population, a clinically meaningful OS trend was observed among patients receiving dostarlimab plus chemotherapy followed by dostarlimab. The OS analysis was done at 33% maturity and statistical significance was not reached.

In April, the European Medicines Agency (EMA) validated GSK’s marketing authorisation application for dostarlimab plus chemotherapy for the treatment of dMMR/MSI-H primary advanced or recurrent endometrial cancer.

About RUBY
RUBY is a two-part global, randomised, double-blind, multicentre phase III trial of patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo. The dual-primary endpoints in Part 1 are investigator-assessed PFS based on the Response Evaluation Criteria in Solid Tumours v1.1 and overall survival (OS). The statistical analysis plan included pre-specified analyses of PFS in the dMMR/MSI-H and intent-to-treat (ITT) populations and OS in the overall population. Pre-specified exploratory analyses of PFS in the mismatch repair proficient (MMRp)/microsatellite stable (MSS) population and OS in the dMMR/MSI-H populations were also performed. RUBY Part 1 included a broad population, including histologies often excluded from clinical trials and had approximately 10% of patients with carcinosarcoma and 20% with serous carcinoma. In Part 2, the primary endpoint is investigator-assessed PFS. Secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.

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.[7]

In the US, Jemperli is indicated for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced endometrial cancer, as determined by a US FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. Jemperli is also indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by a US FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The latter indication is approved in the US under accelerated approval based on tumour response rate and durability of response. Continued approval for this indication in solid tumours may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Jemperli was discovered by AnaptysBio, Inc. 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, commercialisation, and manufacturing of each of these medicines under the agreement.

On June 6, 2023 Genmab A/S (Nasdaq: GMAB) reported that its Chief Financial Officer Anthony Pagano will participate in a fireside chat at the Goldman Sachs 44th Annual Global Healthcare Conference in Dana Point, CA, 11:20 AM PDT on June 13, 2023 (2:20 PM EDT / 8:20 PM CEST) (Press release, Genmab, JUN 6, 2023, View Source [SID1234632511]). A webcast of the fireside chat will be available on Genmab’s website at View Source

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