On June 5, 2023 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that data from the ongoing OPTIMIZE-1 Phase 2 study of the company’s lead asset mitazalimab in 1st line metastatic pancreatic cancer will be presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held in Chicago, June 2-6 (Press release, Alligator Bioscience, JUN 5, 2023, View Source [SID1234632456]).

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The presentation, entitled "Efficacy and Safety of mitazalimab in combination with mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): an interim analysis of the OPTIMIZE-1 phase 1b/2 study", outlines comprehensive data from the interim analysis announced in January 2023.

The data presented at ASCO (Free ASCO Whitepaper) demonstrate that mitazalimab in combination with mFOLFIRINOX is a feasible treatment regimen for 1st line pancreatic cancer patients with encouraging interim efficacy and well-manageable safety profile, consistent with mFOLFIRINOX monotherapy. Combination with mFOLFIRINOX had no impact on mitazalimab pharmacokinetics and the pharmacodynamic biomarker profile in peripheral blood confirmed the immune activation profile typical of mitazalimab.

When administered at 900 μg/kg in combination with mFOLFIRINOX, mitazalimab showed robust anti-tumor activity in 23 mPDAC patients, meriting continued development. An objective response rate (ORR) of 52% was demonstrated with clinically meaningful tumor reduction in 12 of the 23 evaluable patients, which compares favorably to the 31.6%[1] reported with FOLFIRINOX in a similar patient population. The analysis also revealed:

8 patients achieved stable disease resulting in a 91% disease control rate (DCR)
6 of the 7 patients who began treatment at least 6 months prior to the interim analysis cutoff were still on treatment, and of these, 2 patients had been receiving treatment for over 11 months.
With these encouraging results, the OPTIMIZE-1 study passed the futility analysis. Subsequently, the study has completed its full accrual, and top-line data are expected in early Q1 2024.

"ASCO is the most prominent global scientific platform in the field of clinical oncology. Presentation of these strong clinical data for our lead pipeline asset mitazalimab in a very challenging indication highlight the potential of Alligator’s novel immuno-oncology pipeline," said Søren Bregenholt, CEO of Alligator Bioscience. "Mitazalimab is a unique CD40 agonist that is demonstrating not only highly encouraging anti-tumor activity in the treatment of first-line pancreatic cancer, but also a much improved safety profile compared to the previous generations of CD40 agonists. We are truly encouraged by these data and look forward to reporting updated interim data from a larger number of patients and a longer treatment and follow-up later this month, followed by top-line results at the beginning of next year. "

Presentation Details
Abstract Number for Publication: 4139
Abstract Title: Efficacy and Safety of mitazalimab in combination with mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): an interim analysis of the OPTIMIZE-1 phase 1b/2 study
Session Title: Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and Hepatobiliary
Date/Time: Monday 5 June, 2023, 8.00 – 11.00 am CDT
Presenter: Hans Prenen, Head of the Oncology Department at University Hospital, Antwerp, and Investigator in the OPTIMIZE-1 Study

On June 5, 2023 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in the field of cellular metabolism pioneering therapies for rare diseases, reported that the company is scheduled to present at the Goldman Sachs 44th Annual Global Healthcare Conference on Thursday, June 15, 2023, at 11:00 a.m. EDT (Press release, Agios Pharmaceuticals, JUN 5, 2023, View Source [SID1234632455]).

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A live webcast of the presentation can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. A replay of the webcast will be archived on the company’s website for at least two weeks following the presentation.

On June 5, 2023 – Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported an overview of the positive final data from Part C of the TACTI-002 Phase II trial to be presented in a poster presentation at the ASCO (Free ASCO Whitepaper) 2023 Annual Meeting taking place in Chicago, US (Press release, Immutep, JUN 5, 2023, View Source [SID1234632442]).

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Part C of TACTI-002 evaluated eftilagimod alpha (efti), a soluble LAG-3 protein and first-in-class MHC Class II agonist, in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab) in 2nd line head and neck squamous cell carcinoma (2L HNSCC) patients unselected for PDL1 expression (N=37), with disease progression on, or after, platinum-based therapy (± cetuximab).

The combination of efti plus pembrolizumab led to an encouraging overall response rate (ORR) of 29.7% and Complete Response (CR) rate of 13.5% in 2L HNSCC patients, regardless of PD-L1 expression, as per iRECIST (RECIST 1.1 results were comparable). Responses were seen across all PD-L1 subgroups. A promising ORR of 38.5% & 60%, median Overall Survival (mOS) of 12.6 & 15.5 months, and 12-month Overall Survival (OS) rate of 52.0% & 66.7%, were seen in patients with a PD-L1 CPS of ≥1 and a PD-L1 CPS ≥20, respectively. Despite a long median follow up of 39 months, median Duration of Response (mDoR) was not reached. (Table 1)

Results compare favourably to reported results from a registrational trial of anti-PD-1 monotherapy in the same patient population with a PD-L1 CPS ≥1, which showed a 17.3% ORR, mOS of 8.7 months, 12-month OS rate of 40%, a CR rate of 2%, and mDoR of 18.4 months.1 Table 1 – Efficacy Endpoints Across PD-L1 Subgroups in 2nd line HNSCC (TACTI-002, Part C) as per iRECIST Overall (N=37) CPS ≥1 (N=25) CPS ≥20 (N=15) Overall Response Rate (ORR), % 29.7 38.5 60.0 Median Progression-Free Survival (mPFS), months 2.1 2.3 13.6 6-month PFS rate, % 32.4 40.0 53.3 Median Overall Survival (mOS), months 8.7 12.6 15.5 12-month OS rate, % 46.0 52.0 66.7 Median Duration of Response (mDoR), months Not Reached Not Reached Not Reached

Dr. Bernard Doger of START Madrid-FJD, Fundación Jiménez Díaz University Hospital and TACTI-002 and TACTI-003 investigator said, "The high overall and complete response rates for patients in Part C of the TACTI002 trial, taken alongside their long-lasting persistence with the median Duration of Response not reached, provides a strong foundation for the ongoing TACTI-003 trial in 1st line HNSCC. The combination of the MHC Class II agonist, efti, with pembrolizumab is now showing an encouraging overall survival benefit in two different cancer indications."

As seen in multiple clinical trials, efti is generating very durable responses when combined with anti-PD-(L)1 therapies. Notably, one of the five complete responsesthat lasted 28 months (as of the data cut-off) occurred in a patient with negative PD-L1 expression or CPS <1. The safety profile of efti in combination with pembrolizumab continues to be safe and very well tolerated. No new safety signals were observed from Part C of the TACTI-002 Phase II trial. The dual immuno-oncology approach had adverse reactions that led to treatment discontinuation in only two patients (5.1%)2, which compares favorably to the treatment discontinuation rate from adverse reactions with anti-PD-1 monotherapy in the same patient population (6.1%).1

"It’s noteworthy to see efti combined with pembrolizumab generating a response in 29.7% of patients with 2nd line HNSCC, including five patients with complete responses, regardless of PD-L1 expression. In patients expressing PD-L1 CPS >1 or PD-L1 CPS >20, overall survival, progression-free survival, and response rates from the dual immuno-oncology approach compare rather favourably to reported results from anti-PD-1 monotherapy approved for the treatment of platinum refractory metastatic HNSCC," stated Frédéric Triebel, M.D., Ph.D., Immutep’s CSO.

"These final results in 2nd line HNSCC are very encouraging in a difficult to treat patient population. It was the strength of interim results from TACTI-002, along with efti’s potential to address an unmet medical need, that secured FDA Fast Track designation for 1st line treatment of HNSCC. In 1st line HNSCC, we are now focused on completing enrolment for TACTI-003 by mid-year and expect to report top-line results later in H2 of CY2023," said Marc Voigt, Immutep’s CEO.

In addition to the abstract and information that was announced to the ASX on 263 and 31 May 20234, the Final results from TACTI-002 Part C: A Phase II study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in patients with metastatic 2nd line head and neck squamous cell carcinoma unselected for PD-L1 poster will be available on the Posters & Publication section of Immutep’s website following its presentation between 2:15PM-5:15PM EDT at ASCO (Free ASCO Whitepaper) today. KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About Eftilagimod Alpha (Efti) Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track Designation in 1st line HNSCC and in 1st line NSCLC from the United States Food and Drug Administration (FDA).

On June 4, 2023 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported promising data for its novel, potential first-in-class investigational bispecific antibody, ivonescimab, that is being presented today from 8:00 to 11:00am at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL (Press release, Summit Therapeutics, JUN 4, 2023, View Source [SID1234632441]).

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AK112-201 (NCT04736823) is an open-label Phase II study evaluating ivonescimab plus chemotherapy for 174 patents across three cohorts of patients. The poster features data from 135 patients in Cohort 1 of this study: patients who are treatment-naïve with advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors do not have actionable genomic alterations (i.e., patients’ tumors do not have actionable mutations in endothelial growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)).

Notably, this Phase II data set summarizes results to date from 63 patients with squamous histology. These patients experienced a median progression-free survival (PFS) of 11.0 months (95% CI: 9.5 to 16.8 months) and an overall response rate (ORR) of 67% (95% CI: 53% to 78%). After a median follow-up time of 13.3 months, median overall survival (OS) was not reached; although, estimated 9-month OS was 93.2%. The frequency of Grade ≥3 treatment-related adverse events (TRAEs) was 41%. The most frequent treatment-emergent adverse events were anemia, decreased neutrophil counts, and alopecia.

Summit has begun clinical development activities on the Phase III HARMONi-3 study, which intends to evaluate ivonescimab combined with chemotherapy in first-line metastatic squamous NSCLC patients. Summit intends to treat patients in the HARMONi-3 trial during the second half of 2023.

The poster is being presented by Dr. Li Zhang, Sun Yat-Sen University Cancer Center,1 with data generated and analyzed by our collaboration and licensing partner, Akeso, Inc. (HKEX Code: 9926.HK).

In addition to the patients with squamous histology described above, Cohort 1 includes updated data from 72 patients with non-squamous histology. Median PFS experienced by these patients was 12.3 months (95% CI: 8.3 to 19.3 months) and median overall survival was not reached after 13.3 months of median follow-up time. The frequency of Grade ≥3 TRAEs was 19%. The most frequent treatment-emergent adverse events were anemia, decreased neutrophil counts and constipation.

The poster also contains brief updates related to the two other cohorts in this trial:

Cohort 2: Advanced or metastatic non-squamous EGFR-mutated NSCLC patients whose tumor has progressed following treatment with an EGFR-TKI
Cohort 3: Advanced or metastatic NSCLC patients whose tumor has progressed following PD-(L)1 therapy combined with doublet-platinum chemotherapy.
Of the 19 patients in Cohort 2, median PFS of 8.5 months was experienced; median overall survival was not reached. The ORR for patients in this cohort was 68% and the median duration of response (DOR) was 8.5 months. Approximately 32% of patients in this cohort remained on treatment at 12 months.

There were 20 patients in Cohort 3; these patients experienced a median PFS of 7.1 months and median OS was 15.6 months. The ORR for patients in this cohort was 40% and the median DOR was 12.4 months. Approximately 35% of patients in this cohort remained on treatment at 12 months.

Ivonescimab had an acceptable safety profile in combination with platinum-doublet chemotherapy for patients with advanced or metastatic NSCLC who had progressed following an EGFR-TKI, as well as in combination with chemotherapy for patients who had progressed following treatment with a PD-(L)1 inhibitor plus platinum-doublet chemotherapy in this clinical study.

In May 2023, the first patient was treated in Summit’s license territories in the Phase III HARMONi clinical trial. HARMONi intends to evaluate ivonescimab combined with chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI) (AK112-301, NCT05184712).

Ivonescimab, known as SMT112 in the United States, Canada, Europe, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. There is higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal, healthy tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) with over 10 fold increased binding affinity to PD-1 in the presence of VEGF in vitro in tumor cells.2 This tetravalent structure, the intentional design of the molecule, and bringing these two targets into a single bispecific antibody have the potential to steer ivonescimab to the tumor tissue versus healthy tissue, which is intended to improve side effects and safety concerns associated with these targets and has the potential to focus the antitumor activity of both targets. Over 750 patients have been treated with ivonescimab across multiple clinical studies in different indications in China and Australia.

Lung cancer is believed to impact approximately 238,0003 people in the United States each year and approximately 477,0004 in Europe. NSCLC is the most prevalent type of lung cancer and represents approximately 80% to 85% of all incidences.5 Among patients with non-squamous NSCLC, approximately 15% have EGFR-sensitizing mutations in the United States and Europe.6 Patients with squamous histology represent approximately 25% to 30% of NSCLC patients.7

About the ASCO (Free ASCO Whitepaper) Poster

Poster Title: Phase II results of Ivonescimab (AK112/SMT112) a novel PD-1/VEGF bispecific in combination with chemotherapy for first line treatment of advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGA) in EGFR/ALK

ASCO Poster Board Number: 75

ASCO Abstract No.: 9087

ASCO Poster Session: Lung Cancer – Non-Small Cell Metastatic Poster Session.

Session Date & Time: Sunday June 4, 8:00 to 11:00am CT

On June 4, 2023 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported the presentation of biomarker findings from a Phase II study of alisertib plus paclitaxel versus paclitaxel alone (Clinicatrials.gov identifier NCT02187991) in metastatic hormone receptor positive (HR+) and triple negative (TN) breast cancer at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held June 2-6 in Chicago and online (Press release, Puma Biotechnology, JUN 4, 2023, View Source [SID1234632440]). The Phase II trial was conducted through The US Oncology Network. The results of this trial were published by Joyce O’Shaughnessy et al. (Jama Network Open, April 2021) and showed that the addition of alisertib to paclitaxel improved progression-free survival (PFS) among enrolled patients compared with paclitaxel alone (HR, 0.56; 95%CI, 0.37-0.84; P = .005).

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The poster (Abstract #1037, poster #258), entitled, "Association of C-MYC, MYC target gene, and unfolded protein response (UPR) expression with clinical benefit from the oral aurora kinase A (AURKA) inhibitor, alisertib (A), in combination with paclitaxel (P) compared with P alone in patients (Pts) with HER2-negative metastatic breast cancer (MBC)," was presented at the Breast Cancer – Metastatic Poster Session by Sara A. Byron, Ph.D., Integrated Cancer Genomics Division, Translational Genomics Research Institute (TGen), part of City of Hope, on June 4 at 8:00 a.m. CDT. A copy of the poster is available on the Puma Biotechnology website.

Archival tissue samples from patients enrolled in the clinical study were analyzed at TGen. Of the 140 patients enrolled in the trial, 45 from the alisertib plus paclitaxel arm and 51 from the paclitaxel arm had sufficient tissue available for next generation sequencing, and 31 from the alisertib plus paclitaxel arm and 35 from the paclitaxel arm had enough for RNA sequencing/gene set enrichment analysis. The most frequently mutated genes were PIK3CA (45%) and TP53 (44%). No mutations were significantly associated with response or resistance to alisertib plus paclitaxel, including those in PIK3CA, TP53, AKT1, HER2, and CDH1.

Increased MYC RNA expression was observed in tumors from patients who did not derive clinical benefit from paclitaxel alone (defined as PFS less than 6 months) compared to those with benefit from paclitaxel alone (defined as PFS greater than or equal to 6 months). Increased MYC RNA expression was not observed in patients who did not appear to benefit from alisertib plus paclitaxel. Elevated expression of genes involved in MYC activation and in unfolded protein response (a pro-survival mechanism) were enriched in alisertib plus paclitaxel responders compared to paclitaxel responders and were associated with poor response to paclitaxel alone. In 12 patients with exceptional response to alisertib plus paclitaxel (defined as PFS greater than or equal to 12 months), increased expression of genes involved in MYC activation and in epithelial to mesenchymal transition (a hallmark of cancer progression and metastasis) was observed in comparison to cancers from patients whose disease progressed within 6 months of initiating alisertib + paclitaxel (n=11) or those with exceptional response to paclitaxel alone (n=4).

"There continues to be a need for new drugs for the treatment of metastatic ER-positive, HER2-negative breast cancer and triple negative breast cancer," said Joyce A. O’Shaughnessy, M.D., the Celebrating Women Chair in Breast Cancer Research at Baylor University Medical Center, Texas Oncology, and Chair of Breast Cancer Research for the US Oncology Network in Dallas, Texas. "The results of this study and the subsequent biomarker analysis demonstrate that the addition of alisertib to paclitaxel may help to identify which patients are likely to derive the most benefit from alisertib and helps to identify biomarker focused populations that can be studied in future clinical trials of alisertib."

Sara Byron, Ph.D., Research Associate Professor in the Integrated Cancer Genomics Division at TGen, added, "We are pleased to have collaborated with Dr. O’ Shaughnessy on evaluating the effect of alisertib in this breast cancer trial. The biomarkers that were associated with clinical benefit to alisertib appeared to be the ones associated with an aurora kinase A inhibitor like alisertib, and we are hopeful that this work will help identify future patient populations that may benefit from alisertib."

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, "We are very pleased with the results of this biomarker analysis. We are committed to and focused on the development of alisertib in biomarker defined populations who may derive the greatest benefit from treatment with alisertib. This biomarker analysis will be very helpful to the design of the future trials of alisertib that we are planning in hormone receptor positive HER2-negative breast cancer."