On December 2, 2020 Targovax ASA (OSE: TRVX), a clinical stage immuno-oncology company developing immune activators to target hard-to-treat solid tumors, reported that the combination of ONCOS-102 and pembrolizumab (Keytruda) has demonstrated 35% best objective response rate (ORR) in anti-PD1 refractory malignant melanoma (Press release, Targovax, DEC 2, 2020, View Source [SID1234572102]).

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In this two-part, open label phase 1 trial the combination of ONCOS-102 and the anti-PD1 checkpoint inhibitor (CPI) pembrolizumab has been tested in patients with advanced, unresectable melanoma who have had disease progression despite treatment with anti-PD1 CPI. This is a particularly challenging patient population, which is resistant to approved immunotherapies and has few treatment alternatives available.

For the trial overall, tumor responses were observed in 7 out of 20 evaluable patients treated with the ONCOS-102 and pembrolizumab combination, translating into an ORR of 35% by RECIST 1.1 criteria.

In addition, there were multiple examples of responses in non-injected lesions, including 2 patients where a non-injected lesion completely disappeared, indicating that ONCOS-102 can induce systemic anti-tumor immunity.

Prof. Jedd Wolchok, Investigator, Memorial Sloan Kettering Cancer Centre, New York said: "Checkpoint inhibitors have had a significant impact on the way we treat melanoma; however, a subset of patients still does not respond or become resistant to treatment. Therefore, there is a high medical need for immune activating agents to overcome resistance to checkpoint blockade. ONCOS-102 is one such agent that can re-sensitize patients to anti-PD1 therapy. Although these are early data, observing objective responses with some occurring in non-injected lesions in this first exploratory phase 1 trial is encouraging, and we will follow with great interest as ONCOS-102 moves forward into later-stage development."

The trial was designed with two parts assessing different dosing regimens. In Part 1, 9 patients were given 3 intra-tumoral ONCOS-102 injections during the first week, followed by systemic treatment with pembrolizumab every third week for up to 24 weeks. As reported in July 2019, preliminary tumor responses were observed in 3 out of 9 patients in at least one CT scan (see link here). 1 patient has since been determined as non-evaluable (trial inclusion criteria not met), and these numbers have now been updated to 3 out of 8 patients with ORR for Part 1.

12 more patients were enrolled in Part 2 of the trial, where an extended dosing regimen of 12 intra-tumoral ONCOS-102 injections was tested; 4 injections during the first two weeks followed by concomitant administration of ONCOS-102 and pembrolizumab from week 3 and every third week for up to 24 weeks. Tumor responses were observed in 4 out of the 12 patients in at least one CT scan. Notably, the patients in Part 2 had markedly more advanced disease than in Part 1, with the majority diagnosed as stage IV metastatic melanoma when entering the trial. Importantly, both regimens had favorable tolerability profiles, with no safety concerns.

These data are very strong compared to other therapies in development for the same indication in combination with anti-PD1 CPI, including TLR-9 agonists and other oncolytic viruses, which have reported ORR of ca. 25-30%. As such, the observed ONCOS-102 response rate and effect in non-injected lesions can be considered class-leading for the treatment of anti-PD1 refractory malignant melanoma.

Oystein Soug, Chief Executive Officer of Targovax, commented: "These impressive efficacy data in anti-PD1 refractory melanoma are the most important clinical results for Targovax to date. The data clearly confirm our hypothesis that ONCOS-102 can benefit cancer patients resistant to checkpoint inhibition by triggering local and systemic immune activation. They also provide evidence of clinical efficacy and establishes ONCOS-102 as one of the most promising combination partners to checkpoint inhibitors. We will now carefully analyze the immunological data and are planning for a confirmatory melanoma trial for the ONCOS-102 and checkpoint inhibitor combination."

The trial (NCT03003676) was conducted at three sites in the US and one site in Norway, with Memorial Sloan Kettering CC being the coordinating site.

Online presentation:

Targovax management will present the data in a live webcast 2 December 2020 at 10:00 CET. You can join the webcast here. It will be possible to ask questions during the presentation. A replay of the webcast will be available in the Investor section under "Presentations" after the event.

On December 2, 2020 Targovax ASA (OSE: TRVX), a clinical stage immuno-oncology company developing immune activators to target hard-to-treat solid tumors, reported that it will present data from its melanoma and mesothelioma trials in an online webcast at 10:00am CET (Press release, Targovax, DEC 2, 2020, View Source [SID1234572102]).

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With reference to the press release issued 1 December 2020 (see link here), Targovax will present data from its phase 1 trial combining ONCOS-102 and the anti-PD1 checkpoint inhibitor (CPI) pembrolizumab (Keytruda) in patients with advanced, unresectable melanoma who have had disease progression despite treatment with anti-PD1 CPI.

Data from the randomized phase 1/2 trial of ONCOS-102 in combination with standard-of-care (SoC) chemotherapy in patients with malignant pleural mesothelioma (MPM), which was released 24 November 2020 (see link here), will also be presented in the webcast.

The webcast starts at 10:00am CET and you can join the webcast here. It will be possible to ask questions during the presentation. A replay of the webcast will be available in the Investor section under "Presentations" after the event.

On December 2, 2020 RenovoRx, an innovator in targeted cancer therapy, reported it has reached an important milestone with continued momentum and the enrollment of the 100th patient in its phase III TIGeR-PaC clinical trial (Press release, Renovorx, DEC 2, 2020, View Source [SID1234572101]). This trial utilizes the company’s proprietary Trans-Arterial Micro-Perfusion (TAMPTM) technology, a unique method for targeted delivery of chemotherapy to treat solid tumors. The trial is enrolling locally advanced pancreatic cancer patients with inoperable disease in the United States and Europe.

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"During the COVID-19 pandemic, it is vital for patients with cancer symptoms to work with healthcare teams for early diagnosis and treatment planning," said Pashtoon Kasi, MD, MS, oncologist at University of Iowa Health Care and Clinical Assistant Professor of Internal Medicine at Carver College of Medicine. "It is encouraging to see patients continue to enroll in this landmark study when meeting the criteria for the TIGeR-PaC clinical trial, especially despite the situation caused by COVID-19. Hospitals, clinics, and healthcare professionals are working extremely hard to provide safe environments for patients to initiate and keep going with treatment in a multi-disciplinary fashion."

Dr. Kasi added, "We have seen remarkable benefits for pancreatic cancer patients in previous studies with this promising therapy including better quality of life and extension of life. For patients with unresectable pancreas cancer who have limited options, it is of value to be able to provide therapy under this important clinical trial."

The TIGeR-PaC trial’s goal is to determine whether the TAMP procedure can reduce the chance of cancer spreading and extend survival while improving quality of life for pancreatic cancer patients. The study, which currently has approximately 30 active clinical sites, is ultimately expected to involve 200 participants in the US and Europe. To learn more, visit View Source

"We are pleased that we have reached this 100th patient enrollment milestone, especially during this challenging time. The progress we continue to make with this clinical trial is our primary focus as we work toward our goal of improving outcomes for cancer patients," said Shaun Bagai, Chief Executive Officer at RenovoRx. "We appreciate our physician investigators, study coordinators, nurses, clinical teams and, most importantly, our patients for their commitment and participation in this important trial."

RenovoRx recently won the Fierce Innovation Awards – Life Sciences Edition 2020 award for its TAMP technology. The peer reviewed awards program from the publisher of Fierce Biotech and Fierce Pharma honors companies demonstrating innovative solutions, technologies, and services that could make the greatest impact for biotech and pharma companies.

On December 2, 2020 Apotex Corp. reported that its board of directors has appointed Peter Hardwick as President & Chief Executive Officer of Apotex Corp., effective immediately (Press release, Apotex, DEC 2, 2020, View Source;chief-executive-officer-301183018.html [SID1234572100]).

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This announcement serves to formalize Peter’s leadership role, and no other changes to operations or structure are currently being planned. Peter, who has been with Apotex Inc. for 14 years, has served in an interim leadership role with Apotex Corp. since 2019, helping to navigate the business through unprecedented challenges created by the pandemic.

"Peter’s track record as a commercial executive in the pharmaceutical industry has been demonstrated time and again," said Jeff Watson, Global President & Chief Executive Officer, Apotex Inc. "The US market continues to be a growth engine for Apotex and under Peter’s leadership, I have every confidence this will be further accelerated."

On December 2, 2020 Taiho Oncology, Inc. and Astex Pharmaceuticals, Inc. reported that data for oral decitabine and cedazuridine (INQOVI [decitabine and cedazuridine] 35mg/100mg tablets) in intermediate and high-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) will be presented during the 62nd Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting and Exposition (ASH 2020), taking place virtually from December 5-8, 2020 (Press release, Taiho, DEC 2, 2020, View Source [SID1234572099]). Key presentations include:

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Clinical Efficacy and Safety of Oral Decitabine/Cedazuridine in 133 Patients with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML): Michael R. Savona, MD, Chief of Hematology, Cellular Therapy and Stem Cell Transplantation, Associate Director, Division of Hematology/Oncology, Director, Hematology Research and the Early Therapy Program, and Professor of Medicine and Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine (Abstract 1230). Results will be shared online as a poster presentation on December 5, 2020. The abstract for this presentation is available on the ASH (Free ASH Whitepaper) website: View Source
The Direct Medical Costs of Treatment Discontinuation Among Higher-Risk Myelodysplastic Syndrome Patients Receiving Hypomethylating Agents: Namita Joshi, PhD, MS, BPharm, Associate Director, Patient-Centered Outcomes and Real-World Evidence & Data Analytics Centers of Excellence, Pharmerit International (Abstract 1618). Results will be shared online as a poster presentation on December 5, 2020. The abstract for this presentation is available on the ASH (Free ASH Whitepaper) website: View Source
Under-Use of Hypomethylating Agents in Patients with Higher-Risk Myelodysplastic Syndrome in the United States: A Large Population-Based Analysis: Shelby Corman, PharmD, MS, BCPS, Executive Director and Head of the Real-World Evidence & Data Analytics Center of Excellence, Pharmerit International (Abstract 2522). Results will be shared online as a poster presentation on December 6, 2020. The abstract for this presentation is available on the ASH (Free ASH Whitepaper) website: View Source
Additional information can be found at Taiho Oncology’s Medical Booth when the exhibit opens on December 5, 2020.

"We are pleased to present new data for oral decitabine and cedazuridine that adds to the body of evidence supporting treatment for patients living with intermediate and high-risk MDS and CMML," said Harold Keer, MD, PhD, Chief Medical Officer, Astex Pharmaceuticals, Inc. "INQOVI is emerging as an important treatment option that can be taken at home."

The U.S. Food and Drug Administration approved INQOVI in July 2020 for the treatment of adults with intermediate and high-risk MDS and CMML. Taiho Oncology, Inc. previously announced that it has assumed commercialization responsibility from Astex Pharmaceuticals, Inc. and its parent company, Otsuka Pharmaceutical Co., Ltd., for INQOVI in the U.S.

About Myelodysplastic Syndromes (MDS)
Myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic changes in myeloid, erythroid, and megakaryocytic progenitor cells, and associated with cytopenias affecting one or more of the three lineages. U.S. incidence of MDS is estimated to be 10,000 cases per year, although the condition is thought to be under-diagnosed.1,2 The prevalence has been estimated to be from 60,000 to 170,000 in the U.S.3 MDS may evolve into acute myeloid leukemia (AML) in approximately one-third of patients.4 The prognosis for MDS patients is poor; patients die from complications associated with cytopenias (infections and bleeding) or from transformation to AML.

About INQOVI (See View Source)
INQOVI is an orally administered, fixed-dose combination of the approved anti-cancer DNA hypomethylating agent, decitabine, together with cedazuridine,5 an inhibitor of cytidine deaminase.6 By inhibiting cytidine deaminase in the gut and the liver, INQOVI is designed to allow for oral delivery of decitabine over five days in a given cycle to achieve comparable systemic exposure to IV decitabine (geometric mean ratio of the 5-day cumulative decitabine area-under-the-curve following 5 consecutive once daily doses of INQOVI compared to that of intravenous decitabine was 99% (90% CI:93, 106).7 The phase 1 and phase 2 clinical study results have been published in Lancet Haematology8 and Blood,9 respectively. The phase 3 ASCERTAIN study data was presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting in Orlando, Florida, in December 2019 by Dr. Garcia-Manero.10

INDICATIONS
INQOVI is indicated for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Myelosuppression
Fatal and serious myelosuppression can occur with INQOVI. Based on laboratory values, new or worsening thrombocytopenia occurred in 82% of patients, with Grade 3 or 4 occurring in 76%. Neutropenia occurred in 73% of patients, with Grade 3 or 4 occurring in 71%. Anemia occurred in 71% of patients, with Grade 3 or 4 occurring in 55%. Febrile neutropenia occurred in 33% of patients, with Grade 3 or 4 occurring in 32%. Myelosuppression (thrombocytopenia, neutropenia, anemia, and febrile neutropenia) is the most frequent cause of INQOVI dose reduction or interruption, occurring in 36% of patients. Permanent discontinuation due to myelosuppression (febrile neutropenia) occurred in 1% of patients. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate progression of underlying MDS.

Fatal and serious infectious complications can occur with INQOVI. Pneumonia occurred in 21% of patients, with Grade 3 or 4 occurring in 15%. Sepsis occurred in 14% of patients, with Grade 3 or 4 occurring in 11%. Fatal pneumonia occurred in 1% of patients, fatal sepsis in 1%, and fatal septic shock in 1%.

Obtain complete blood cell counts prior to initiation of INQOVI, prior to each cycle, and as clinically indicated to monitor response and toxicity. Administer growth factors and anti–infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose as recommended.

Embryo-Fetal Toxicity
INQOVI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise patients to use effective contraception during treatment and for 6 months (females) or 3 months (males) after last dose.

ADVERSE REACTIONS
Serious adverse reactions in > 5% of patients included febrile neutropenia (30%), pneumonia (14%), and sepsis (13%). Fatal adverse reactions included sepsis (1%), septic shock (1%), pneumonia (1%), respiratory failure (1%), and one case each of cerebral hemorrhage and sudden death.

The most common adverse reactions (≥ 20%) were fatigue (55%), constipation (44%), hemorrhage (43%), myalgia (42%), mucositis (41%), arthralgia (40%), nausea (40%), dyspnea (38%), diarrhea (37%), rash (33%), dizziness (33%), febrile neutropenia (33%), edema (30%), headache (30%), cough (28%), decreased appetite (24%), upper respiratory tract infection (23%), pneumonia (21%), and transaminase increased (21%). The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were leukocytes decreased (81%), platelet count decreased (76%), neutrophil count decreased (71%), and hemoglobin decreased (55%).

USE IN SPECIFIC POPULATIONS
Lactation
Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with INQOVI and for at least 2 weeks after the last dose.

Renal Impairment
No dosage modification of INQOVI is recommended for patients with mild or moderate renal impairment (creatinine clearance [CLcr] of 30 to 89 mL/min based on Cockcroft-Gault). Due to the potential for increased adverse reactions, monitor patients with moderate renal impairment (CLcr 30 to 59 mL/min) frequently for adverse reactions. INQOVI has not been studied in patients with severe renal impairment (CLcr 15 to 29 mL/min) or end-stage renal disease (ESRD: CLcr <15 mL/min).