On May 27, 2022 Targovax ASA (OSE: TRVX), reported that publication of the two ONCOS-102 abstracts accepted for presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 3-7 June 2022 (Press release, Targovax, MAY 27, 2022, View Source [SID1234615167]). The posters will present clinical results from the completed phase 1/2 trials in malignant pleural mesothelioma and in heavily pre-treated, MS-stable colorectal or ovarian cancer with peritoneal metastasis.

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First poster title: Final survival outcomes and immune biomarker analysis of a randomized, open-label, phase I/II study combining oncolytic adenovirus ONCOS-102 with pemetrexed/cisplatin (P/C) in patients with unresectable malignant pleural mesothelioma (MPM)
Session Title: Lung Cancer – Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Time: Monday 6 June 2022, 8:00-11:00 AM CDT, Abstract 8561
Presenter: Dr Santiago Ponce, Medical Oncology, Hospital 12 Octubre, Madrid, Spain

The poster summarizes the overall findings from the completed, randomized phase 1/2 trial in 31 patients with MPM; 20 patients received intra-tumoral (IT) ONCOS-102 in combination with standard of care (SoC) chemotherapy and 11 patients in a control group received SoC chemotherapy only.

In the randomized part of the trial, the 30-month overall survival (OS) rate was 34.3% in the ONCOS-102 treated group (n=14) vs. 18.2% in the SoC-only control group (n=11). In first-line patients, the ONCOS-102 group achieved a median overall survival (mOS) of 25.0 months (n=8) vs. 13.5 months mOS in the SoC-only control group (n=6). The ONCOS-102 first-line mOS compares favorably to SoC historical control studies reporting mOS of 12-16 months1, as well as the combination of nivolumab and ipilimumab which demonstrated mOS of 18.1 months in a phase 3 trial that led to FDA approval2. Tumor biopsy immune cell analyses revealed strong T-cell infiltration induced by ONCOS-102 in patients with partial response (PR) or stable disease (SD), but not in progressors. These observations were confirmed by RNAseq gene expression analysis. The breadth and strength of immune response induced by ONCOS-102 correlated with both tumor response and survival. Further clinical trials in MPM are clearly warranted to validate these positive findings in a larger patient cohort.

Second poster title: Study to evaluate intraperitoneal (IP) ONCOS-102 with systemic durvalumab in patients with peritoneal disease who have epithelial ovarian (OC) or metastatic colorectal cancer (CRC): Phase 2 results
Session Title: Development Therapeutics, Immunotherapy
Time: Sunday 5 June 2022, 8:00-11:00 AM CDT, Abstract 2600
Presenter: Dr Dmitriy Zamarin, Memorial Sloan Kettering Cancer Center, New York, USA

The poster reports clinical data from the ONCOS-102 phase 1/2 combination trial with anti-PD-L1 checkpoint inhibitor durvalumab in heavily pre-treated, MS-stable CRC (n=36) or OC (n=19) with peritoneal metastases. This is a patient population with few treatment alternatives that only offer marginal efficacy and where checkpoint inhibitor monotherapy does not have any meaningful activity. The trial was managed by an external consortium with Ludwig Cancer Research as sponsor, where Targovax was a collaboration partner.

This is the first time ONCOS-102 has been administered IP and in combination with an anti-PD-L1 checkpoint inhibitor. IP delivery of ONCOS-102 was demonstrated to be feasible and well-tolerated, both as monotherapy and in combination with systemic durvalumab. Whereas the initial OC cohort did not meet the efficacy criteria and was closed, the initial CRC cohort met the efficacy criteria and was expanded. In the full CRC cohort (n=36) two patients remained progression free at the end of the study (week 24), but the primary efficacy endpoint of 4 patients remaining progression free at week 24 was not met.

Tumor biopsy immune cell analysis showed increased T-cell infiltration in several patients, confirming that IP administered ONCOS-102 can induce immune activation in heavily pre-treated, immunologically silent solid tumors. Of note, the selected IP dose was the same as used for IT delivery of ONCOS-102 (3×1011 V.P.), although IP delivery is expected to result in lower tumor exposure to the virus relative to IT. Hence, higher doses of IP delivered ONCOS-102 could potentially enhance both the immunological response and clinical activity.

Dr. Lone Ottesen, Chief Medical Officer of Targovax, said: "We are very pleased to have two ONCOS-102 studies accepted for presentation at ASCO (Free ASCO Whitepaper) this year, which is a very important forum to showcase and discuss our clinical data with international experts in the field. In our exploratory clinical program we have now demonstrated that ONCOS-102 can be delivered safely intra-tumorally and intra-peritoneally in combination with PD-1 and PD-L1 checkpoint inhibitors, as well as chemotherapy. Importantly, we have also seen robust immunological and clinical activity in solid tumors of different origins. This gives us confidence to bring ONCOS-102 forward into later stage development, with the first step being a multi-cohort phase 2 trial in PD1-refractory melanoma where we will test several I-O combinations, including the second-generation anti-CTLA4 checkpoint inhibitor botensilimab."

About ASCO (Free ASCO Whitepaper)
American Society of Clinical Oncology Annual Meeting, ASCO (Free ASCO Whitepaper) 2022 will be held in McCormick Place, Chicago, Illinois, United States between 3-7 June 2022.

The 2022 ASCO (Free ASCO Whitepaper) Annual Meeting Program will offer presentations on the latest research in cancer care. This year’s program will feature sessions complementing the meeting’s theme: Advancing Equitable Cancer Care Through Innovation.

On May 26, 2022 SOTIO Biotech, a clinical stage immuno-oncology company owned by PPF Group, reported updated interim safety and efficacy data from its Phase 1/1b AURELIO-03 dose escalation study of the IL-2/IL-15 receptor βγ superagonist, SOT101, as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors (Press release, SOTIO, MAY 26, 2022, View Source [SID1234626226]). Data from the study show that SOT101 has a favorable safety profile. The recommended Phase 2 dose was defined at 12 µg/kg SOT101.

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The AURELIO-03 study is an open label, single arm Phase 1/1b dose escalation study to determine the recommended Phase 2 dose and to evaluate the preliminary efficacy of SOT101 in patients with advanced solid tumors either as a monotherapy or in combination with pembrolizumab. SOT101 is administered subcutaneously on days 1, 2, 8, and 9 of every three-week cycle. 30 patients were treated on monotherapy dose levels 0.25 to 15 μg/kg and twenty-one patients on combination therapy dose levels 1.5 to 12 μg/kg.

Interim results of SOT101 as a monotherapy demonstrated four patients pretreated with checkpoint inhibitor (CPI) with confirmed stable disease. A partial response was confirmed in one patient with skin squamous cell carcinoma whose tumor was CPI-refractory. The preliminary efficacy is currently being further evaluated in an ongoing monotherapy extension in skin squamous cell carcinoma, melanoma, and renal cell cancer.

In 19 patients with at least one post-baseline tumor assessment across all dose levels who were treated with SOT101 in combination with pembrolizumab, one complete response in a patient with mesothelioma, four partial responses and 10 confirmed stable diseases have been reported.

The adverse event profile of SOT101 in combination with pembrolizumab was in line with the adverse event profile of either compound as monotherapy. No additive toxicity was seen when combining SOT101 with pembrolizumab. For both monotherapy and combination treatment, the recommended Phase 2 dose of SOT101 was established at 12 μg/kg.

This data will be presented by principal investigator Dr. Elena Garralda from the Vall D’Hebron Institute of Oncology, Barcelona, Spain at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois on Saturday, June 4, 2022.

"Despite decades of progress in clinical oncology, the difficulty of treating solid tumors has remained a significant challenge for physicians," said Radek Spisek, M.D., Ph.D., chief executive officer of SOTIO. "Given the promising results from our first-in-human study of SOT101, we are greatly encouraged to have observed excellent preliminary safety and efficacy data both as a monotherapy and in combination with pembrolizumab. We look forward to initiating a basket study of SOT101 in combination with KEYTRUDA to evaluate efficacy and safety in patients with selected advanced or refractory solid tumors. This large Phase 2 AURELIO-04 trial in collaboration with MSD will be initiated in the coming weeks."

Dr. Garralda added: "The patients in this study are some of the hardest to treat, some with up to nine prior lines of therapy, so the clinical benefit observed in the AURELIO-03 study is especially encouraging. These data highlight the potential impact of SOT101 on the treatment landscape for solid tumors."

The presentation from ASCO (Free ASCO Whitepaper) is available below:

ASCO 2022 – AURELIO-03 results.pdf

About SOT101:
SOT101 (SO-C101) is a subcutaneously administered IL-15Rβγ superagonist that is fused to the sushi+ domain of the IL-15 receptor α chain. SOT101 has demonstrated strong preclinical in vivo efficacy in various tumor models showing increased long-term survival and tumor regression, as well as a favorable toxicology profile. SOT101 has been shown in pre-clinical models to synergize with checkpoint inhibitors and antibody therapies exerting ADCC.

On May 26, 2022 Chiome Bioscience Inc. reported joint research agreement with Kidswell Bio Corporation (Press release, Chiome Bioscience, MAY 26, 2022, View Source [SID1234625711]). The collaborative research makes us join their ongoing research project to develop therapeutic antibody for cancer.

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Our mission is to shine the light on unmet medical needs through our research project of drug discovery and development. This collaborative research will expect to merge our research functions and experiences with novel antibody drug discovery project. We will continue to discuss the extended collaboration scheme with Kidswell Bio in case our joint research make the progress pushing the project up to the therapeutic drug development stage.

On May 26, 2022 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported the publication of an abstract at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Onconova, MAY 26, 2022, View Source [SID1234615195]). Featured in the abstract are preclinical data from in vitro and cell-based assays that demonstrate how narazaciclib’s inhibitory profile differentiates it from the FDA-approved CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib.

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Key data and conclusions from the abstract include:

Narazaciclib, abemaciclib, palbociclib, and ribociclib each have strong affinity for CDK4/cyclin D1, with Kd values of 0.18 nM, 0.08 nM, 0.75 nM, and 1.3 nM, respectively.

Narazaciclib and abemaciclib have similar affinities against CDK family members, including nM activity against CDK2/cyclin A, which may play a role in resistance to palbociclib and ribociclib.

Narazaciclib’s inhibitory activity against GSK3β, a kinase whose inhibition putatively causes tolerability issues related to diarrhea, is ~29 times less than that of abemaciclib.

Cellular kinase assays showed narazaciclib’s highest inhibitory activity to be against CDK4/6, CSF1R, (supports pro-tumor immune suppression), and NUAK1/ARK 5 (associated with poor prognosis in multiple cancers and implicated in cancer cell migration, invasion, and metastasis).

Cellular Thermal Shift Assay (CETSA) and integrative Inferred Kinase Activity (INKA) analysis showed that narazaciclib is associated with and modulated unique signaling pathways resulting in specific deregulated phosphorylation patterns when compared to palbociclib treated cells.
Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova and co-author of the abstract, commented, "Though revolutionary and commercially successful, currently available CDK4/6 inhibitors are limited by tolerability and safety issues as well as the unfortunate reality of primary and acquired drug resistance. This creates a pressing unmet need for novel agents that may overcome these shortcomings and provide patients with durable clinical benefit. Narazaciclib’s decreased affinity for targets associated with poor tolerability, together with its increased inhibitory activity against kinases implicated in metastasis, cancer cell survival, immune suppression, and drug resistance, suggests it may address this need. We continue to explore this hypothesis in narazaciclib’s clinical program and remain on track to establish a recommended Phase 2 dose by the end of the year."

A copy of the abstract, titled, "Narazaciclib’s kinase inhibitory activity is differentiated from approved CDK4/6 inhibitors in preclinical models," is available on the ASCO (Free ASCO Whitepaper) Annual Meeting website.

On May 26, 2022 Checkmate Pharmaceuticals, Inc. (NASDAQ: CMPI) ("Checkmate"), a clinical stage biotechnology company focused on developing its proprietary technology to harness the power of the immune system to combat cancer, reported the University of Iowa Holden Comprehensive Cancer Center’s presentation of preliminary data from an investigator-sponsored phase 1/2 trial evaluating vidutolimod, a first-in-class, immunostimulatory, noninfectious virus-like particle (VLP) containing a CpG-A Toll-like receptor 9 (TLR9) agonist (Press release, Checkmate Pharmaceuticals, MAY 26, 2022, View Source [SID1234615194]). The early phase trial is investigating intratumoral vidutolimod therapy in combination with intravenous pembrolizumab in patients with relapsed lymphoma. The objective of this study is to determine the dose of vidutolimod that, in combination with pembrolizumab, has optimal clinical efficacy and acceptable toxicity in patients with relapsed lymphoma who have failed at least one line of therapy. In addition to the funding provided by Checkmate, the ongoing study is supported by NCI grant P50 CA97274 to the University of Iowa/Mayo Clinic (UI/MC) Lymphoma SPORE (specialized program of research excellence).

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Preliminary results from an early-phase trial of in situ immunization of lymphoma with a virus-like particle containing a TLR9 agonist combined with anti–PD-1 therapy (Abstract #: 2639: NCT03983668)

During the 2022 ASCO (Free ASCO Whitepaper) Developmental Therapeutics—Immunotherapy Poster Session on Sunday, June 5 at 9:00am ET, Umar Farooq, M.D., Clinical Associate Professor of Internal Medicine at University of Iowa Hospitals & Clinics, principal investigator, and study sponsor, will present preliminary safety, response and translational laboratory data from 7 enrolled patients with relapsed lymphoma.
Key highlights from the presentation include:

Preliminary results suggest that in situ immunization with vidutolimod plus systemic pembrolizumab had clinical activity in a variety of lymphomas in 5 of 7 patients studied
No significant adverse effects (AEs) were reported after the 4-hour observation period other than mild headache or fatigue lasting only through day 1
Consistent with preclinical data, generation of anti-Qβ antibodies after the initial subcutaneous (SC) vidutolimod dose correlated with response to study treatment; further evaluation in additional patients is needed to confirm these initial observations
Additional evaluation of complex interactions between cells in the tumor microenvironment in response to vidutolimod will be needed to understand these findings
Study enrollment is ongoing and given the common use of B cell depleting therapies for the treatment of certain lymphomas, the study was modified to require generation of anti-Qβ antibodies after the initial SC dose of vidutolimod before patients receive IT therapy.

"Our understanding of the immune and therapeutic responses to intratumoral vidutolimod with checkpoint inhibitors continues to grow stronger based on these data," said Art Krieg, M.D., Founder and Chief Scientific Officer of Checkmate. "These initial observations provide valuable insights into the mechanism of action of vidutolimod and reinforce earlier preclinical data from the Iowa team that suggest the activity of vidutolimod requires the generation of anti-Qβ antibodies. We look forward to the continued investigation of vidutolimod in combination with immune checkpoint inhibitors to improve available treatment options for people with lymphoma and other difficult to treat cancers."