On September 30, 2019 Geron Corporation (Nasdaq: GERN) reported that the United States Food and Drug Administration (FDA) has granted Fast Track designation to imetelstat for the treatment of adult patients with Intermediate-2 or High-risk myelofibrosis (MF) whose disease has relapsed after or is refractory to janus kinase (JAK) inhibitor treatment, or relapsed/refractory MF (Press release, Geron, SEP 30, 2019, View Source [SID1234539928]). The Fast Track designation includes patients with primary MF and MF developed after essential thrombocythemia or polycythemia vera. This is the same patient population that was studied in Geron’s IMbark Phase 2 clinical trial. There are currently no marketed drugs specifically approved for relapsed/refractory MF, representing a significant unmet medical need. Geron plans to conduct an End of Phase 2 meeting with the FDA by the end of the first quarter of 2020 to determine if there is a regulatory path forward for imetelstat in relapsed/refractory MF.

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 FDA’s Fast Track Program is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious conditions and supported by data that demonstrate the potential to address an unmet medical need. Fast Track designation provides opportunities for frequent interactions with FDA review staff, including meetings to discuss the drug’s development plan and to ensure the collection of appropriate data needed to support approval. Through the Fast Track Program, a product candidate may be eligible for priority review, if supported by the clinical data, and for the ability to submit completed sections of a New Drug Application (NDA) on a rolling basis as data become available prior to completion of the full application.

About Myelofibrosis

Myelofibrosis (MF), a type of myeloproliferative neoplasm, is a chronic blood cancer in which abnormal or malignant precursor cells in the bone marrow proliferate rapidly, causing scar tissue to form (fibrosis). As a result, normal blood production in the bone marrow is impaired and may shift to other organs, such as the spleen and liver, which can cause them to enlarge substantially. People with MF may have abnormally low or high numbers of red blood cells, white blood cells or platelets in the blood or bone marrow. MF patients can also suffer from debilitating constitutional symptoms, such as fever, weight loss, night sweats, and itching (pruritus). MF patients have shortened survival, and their disease may transform to acute myeloid leukemia.

The number of people living with MF in the United States is estimated at 13,000 patients, with approximately 3,000 new cases diagnosed each year. There are currently only two drugs approved by the FDA for treating MF patients. The most widely used drug therapy for MF has a discontinuation rate of 75% after five years of treatment. Once patients discontinue treatment with this drug due to failure or lack of response, there are no specifically approved therapies, and the median overall survival for these MF patients is approximately 14 to 16 months, representing a significant unmet medical need.

About IMbark

IMbark is a Phase 2 clinical trial to evaluate two starting dose levels of imetelstat (either 4.7 mg/kg or 9.4 mg/kg administered by intravenous infusion every three weeks) in patients with Intermediate-2 or High-risk MF who have relapsed after or are refractory to prior treatment with a JAK inhibitor. The co-primary efficacy endpoints for the trial are spleen response rate and symptom response rate. Key secondary endpoints are safety and overall survival. IMbark is closed to new patient enrollment.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the suppression of malignant progenitor cell clone proliferation, which allows potential recovery of normal hematopoiesis. Ongoing clinical studies of imetelstat consist of IMerge, a Phase 2/3 trial in lower risk myelodysplastic syndromes (MDS), and IMbark, a Phase 2 trial in Intermediate-2 or High-risk myelofibrosis (MF). Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis-stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus kinase (JAK) inhibitor treatment.

On September 30, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported positive results from the Phase III IMvigor130 study evaluating Tecentriq (atezolizumab) plus platinum-based chemotherapy versus chemotherapy alone for the first-line (initial) treatment of people with previously untreated locally advanced or metastatic urothelial carcinoma (mUC) eligible and ineligible for cisplatin chemotherapy (Press release, Hoffmann-La Roche, SEP 30, 2019, View Source [SID1234539927]). In the study, Tecentriq plus chemotherapy showed a statistically significant improvement in progression-free survival (PFS) compared with platinum-based chemotherapy alone (median PFS=8.2 versus 6.3 months; hazard ratio (HR)=0.82, 95% CI: 0.70-0.96; p=0.007). Encouraging overall survival (OS) results were observed for Tecentriq plus chemotherapy compared with chemotherapy alone in the intention-to-treat population (ITT), however these data did not reach statistical significance at this interim analysis (median OS=16.0 versus 13.4 months; HR=0.83, 95% CI: 0.69-1.00). Safety in the Tecentriq plus chemotherapy arm appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination.

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!

"We are pleased with these positive results from the IMvigor130 study, which show Tecentriq plus chemotherapy may provide a meaningful benefit for people newly diagnosed with advanced bladder cancer," said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. "There remains a high unmet need for people with advanced bladder cancer, where chemotherapy alone is the current standard of care. These results reinforce the role of immunotherapy in treating this aggressive disease."

Additional data from the Tecentriq monotherapy arm were also presented in the ITT population and people with different levels of PD-L1 expression. Encouraging OS results were observed with Tecentriq monotherapy in people with high PD-L1 expression (IC2/3), however, these data were not formally tested per the hierarchical design of the trial. Follow up will continue until the next analysis.

These data will be presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress Presidential Symposium at 17:53–18:05 CEST (Abstract LBA14) and were featured in the official ESMO (Free ESMO Whitepaper) press programme.

Tecentriq was the first cancer immunotherapy approved in advanced bladder cancer. Currently, there are four ongoing Phase III studies evaluating Tecentriq alone and in combination with other medicines in early and advanced bladder cancer. Roche has an extensive development programme for Tecentriq, including multiple ongoing and planned Phase III studies, across lung, genitourinary, skin, breast, gastrointestinal, gynaecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

About the IMvigor130 study
IMvigor130 is a multicentre, partially blinded, randomised Phase III study, evaluating the efficacy and safety of Tecentriq in combination with chemotherapy or alone versus chemotherapy alone for people with mUC who have not received prior systemic therapy for metastatic disease. It enrolled 1,213 people who received:

Tecentriq plus platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin), or
Tecentriq, or
Platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin) plus placebo (control arm).
In the Tecentriq combination arm, the co-primary endpoints are OS and PFS, as assessed by investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). The secondary endpoints are objective response rate and duration of response, as assessed by investigator using RECIST v1.1, and independent review facility assessed PFS.

A summary of the key study results is included below:

Safety for the Tecentriq plus chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination. There appeared to be no worsening of tolerability with the addition of Tecentriq to chemotherapy compared with chemotherapy alone. All cause Grade 3-4 adverse events (AEs) were reported in 85% of people receiving Tecentriq plus chemotherapy, compared with 86% of people receiving chemotherapy alone. Treatment-related Grade 3-4 AEs were reported in 83% of people receiving Tecentriq plus chemotherapy, compared with 81% of people receiving chemotherapy alone. Any Grade AEs leading to any treatment discontinuation of Tecentriq or placebo were observed in 11% and 7% of people in the combination arm compared with the chemotherapy arm respectively.

About bladder cancer
In 2018, there were over half a million new cases of bladder cancer diagnosed globally, with around 200,000 deaths from the disease.1 Urothelial carcinoma, which develops in the cells of the bladder lining, is the most common type of bladder cancer, accounting for about 90% of all cases.2 In total, 30% of cases are considered advanced based on muscle-invasive or metastatic disease.3 There remains a high unmet need for people facing previously untreated advanced bladder cancer. Despite improvements in tolerability, there have been no efficacy improvements for more than 30 years with chemotherapy as standard of care, and patients continue to experience poor outcomes.4,5

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer, and in PD-L1-positive metastatic triple-negative breast cancer.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.

To learn more about the Roche approach to cancer immunotherapy please follow this link: View Source

On September 30, 2019 Dynavax Technologies Corporation (NASDAQ: DVAX), reported that Ryan Spencer, Senior Vice President, Commercial, and Interim Co-President, will present at the 2019 Cantor Global Healthcare Conference on Friday, Oct. 4, at 12 p.m. E.T (Press release, Dynavax Technologies, SEP 30, 2019, View Source [SID1234539926]).

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 presentation will be webcast and may be accessed at the "Events & Presentations" section of the Company’s website at View Source

On September 30, 2019 Deciphera Pharmaceuticals, Inc. (Nasdaq:DCPH), a clinical-stage biopharmaceutical company addressing key mechanisms of tumor drug resistance, reported the late-breaking presentation of results from the INVICTUS pivotal Phase 3 clinical study of ripretinib in patients with advanced gastrointestinal stromal tumors (GIST) in an oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress (Press release, Deciphera Pharmaceuticals, SEP 30, 2019, View Source [SID1234539925]).

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!

"For GIST patients who have failed currently approved agents, there exists an urgent need for effective and well-tolerated treatment options," said Margaret von Mehren, MD, Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. "With a statistically significant improvement observed in progression free survival compared with placebo, and a clinically meaningful increase in overall survival compared with placebo, ripretinib represents a potential standard of care for patients harboring a broad spectrum of mutations known to drive GIST in patients who have no approved treatment options."

"Results from the INVICTUS study support our belief that ripretinib has the potential to transform the current treatment landscape for advanced GIST," said Steve Hoerter, President and Chief Executive Officer of Deciphera. "We are now working with the FDA as we prepare the NDA submission for ripretinib, which we expect in the first quarter of 2020."

Today’s presentation featured new data as well as top-line results previously announced by the Company in August 2019. A copy of the presentation will be available following the session at www.deciphera.com.

INVICTUS Study Results

The INVICTUS Phase 3 clinical study is a randomized (2:1), double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability, and efficacy of ripretinib compared to placebo in 129 patients with advanced GIST whose previous therapies have included at least imatinib, sunitinib, and regorafenib. As previously reported, the study achieved the primary endpoint of improved progression free survival (PFS) compared to placebo in patients with fourth-line and fourth-line plus GIST, as determined by blinded independent central radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Progression Free Survival (PFS)

Ripretinib significantly reduced the risk of disease progression or death by 85% compared to placebo and demonstrated a median PFS of 6.3 months compared to 1.0 month in the placebo arm (HR=0.15, 95% CI (0.09,0.25), p<0.0001). This PFS benefit was consistent across all assessed patient subgroups.

Objective Response Rate (ORR) and Duration of Response

Eight patients (9.4%) had a confirmed objective response with ripretinib (p=0.0504) compared to no confirmed responses in the placebo arm, as measured by blinded independent central review, which was not statistically significant. As of the cutoff date of May 31, 2019, the median duration of response had not been reached with seven of the eight patients still responding to treatment. All responders had partial responses.

Overall Survival (OS)

Ripretinib reduced the risk of death by 64% compared to placebo and demonstrated a median OS of 15.1 months vs. 6.6 months in the placebo arm (HR=0.36, 95% CI (0.20,0.62), nominal p=0.0004). Since statistical significance was not achieved for the secondary endpoint of ORR, the hypothesis testing of OS was not formally performed. According to the pre-specified hierarchical testing procedure of the endpoints, the hypothesis testing of OS cannot be formally conducted unless the test for ORR is statistically significant.

Safety

Ripretinib was generally well tolerated and the adverse events observed in INVICTUS were consistent with data from previously presented Phase 1 study results. Treatment-emergent adverse events (TEAEs) occurred in 99% of patients on the ripretinib arm compared to 98% on the placebo arm. Grade 3 or 4 TEAEs occurred in 49% of patients on the ripretinib arm compared to 44% on the placebo arm. Grade 3 or 4 TEAEs greater than 5% of patients on the ripretinib arm were anemia (9%), abdominal pain (7%) and hypertension (7%). Grade 3 or 4 TEAEs greater than 5% of patients on the placebo arm were anemia (14%). TEAEs leading to dose reduction occurred in 7% of patients on the ripretinib arm compared to 2% on the placebo arm. TEAEs leading to dose interruption occurred in 24% of patients on the ripretinib arm compared to 21% on the placebo arm. TEAEs leading to study treatment discontinuation occurred in 8% of patients on the ripretinib arm compared to 12% of patients on the placebo arm. TEAEs leading to death occurred in 6% of patients on the ripretinib arm compared to 23% on the placebo arm.

New Drug Application (NDA) Submission

Based on the positive INVICTUS data, the Company expects to submit an NDA to the U.S. Food and Drug Administration (FDA) for ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib in the first quarter of 2020.

About the INVICTUS Phase 3 Study

The INVICTUS Phase 3 clinical study is a randomized, double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability, and efficacy of ripretinib compared to placebo in patients with advanced GIST whose previous therapies have included imatinib, sunitinib, and regorafenib. This study was designed to provide evidence of clinical benefit in fourth-line and fourth-line plus patients with GIST that would be required to secure a regulatory approval. Patients were randomized 2:1 to either 150 mg of ripretinib or placebo once daily. The primary efficacy endpoint is progression-free survival (PFS) as determined by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints as determined by independent radiologic review using modified RECIST include Objective Response Rate (ORR), Time to Tumor Progression (TTP) and Overall Survival (OS). See www.clinicaltrials.gov for further information (NCT03353753).

About Ripretinib

Ripretinib is an investigational tyrosine kinase switch control inhibitor that was engineered to broadly inhibit KIT and PDGFRα mutated kinases by using a unique dual mechanism of action that regulates the kinase switch pocket and activation loop. Ripretinib is currently in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, or GIST, systemic

mastocytosis, or SM, and other cancers. Ripretinib inhibits initiating and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18, involved in GIST, as well as the primary D816V exon 17 mutation involved in SM. Ripretinib also inhibits primary PDGFRα mutations in exons 12, 14 and 18, including the exon 18 D842V mutation, involved in a subset of GIST. In June 2019, the U.S. FDA granted Fast Track Designation to ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib.

Deciphera Pharmaceuticals has an exclusive license agreement with Zai Lab (Shanghai) Co., Ltd. for the development and commercialization of ripretinib in Greater China (Mainland China, Hong Kong, Macau and Taiwan). Deciphera Pharmaceuticals retains development and commercial rights for ripretinib in the rest of the world.

On September 30, 2019 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported Jarrod Longcor, chief business officer of Cellectar, presented data from the diffuse large B cell lymphoma (DLBCL) cohort in the company’s Phase 2 CLOVER-1 study of CLR 131 in relapsed or refractory select B-cell malignancies at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2019 being held from September 27 – October 1, 2019 in Barcelona, Spain (Press release, Cellectar Biosciences, SEP 30, 2019, View Source [SID1234539924]).

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 oral presentation, entitled: "Interim Evaluation of a Targeted Radiotherapeutic, CLR 131, in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients (R/R DLBCL)," featured data from 6 subjects who received a single 30-minute intravenous (IV) dose of 25mCi/m2 of CLR 131. Data showed durable responses, including a 33% overall response rate (ORR), a 16.6% complete response rate (CR) and a 50% clinical benefit rate (CBR). All patients enrolled in the study received an average of 3 prior lines of systemic therapy, 5 of 6 patients were refractory to at least one prior line of therapy. Importantly, CLR 131 showed activity against both germinal center and activated DLBCL. In a patient for whom cytogenetics was available, CLR 131 showed activity against c-Myc and BCL-2 mutation (single & dual-hit) positive patients. As required by the Lugano Criteria for Response, the patient who experienced a CR had a total reduction in tumor volume of greater than 99% and continues to be a CR at 510+ days post dosing. This patient was refractory to two prior treatment lines, which included the combination regimen RICE.

Analysis of dosing showed that the disease control rate and progression free survival were markedly improved in patients receiving a dosing ratio of 1.2% or greater (drug to tumor volume) versus those receiving below a 1.2% dosing ratio. Finally, the most frequent adverse events (AE) in DLBCL patients were consistent with prior studies of CLR 131; the majority of AEs being hematologic in nature and predominately Grades 1 and 2.

"The data presented show an encouraging overall response rate including a complete response at the time of the interim assessment after a single 30-minute IV dose of 25mCi/m2 of CLR 131. We remain optimistic that CLR 131 has the potential to provide a meaningful treatment option for a variety of lymphoma patients and look forward to reporting additional data from this Phase 2 CLOVER-1 study in 2019," said James Caruso, president and CEO of Cellectar. "The study remains ongoing and, based on this cohort and additional data from an ongoing dose escalation Phase 1 study, patients in the Phase 2 CLOVER-1 study are now receiving a higher 37.50 mCi/m2 fractionated dose administered in two 30-minute infusions of 18.75mCi/m2."

About the Phase 2 CLOVER-1 Trial

CLOVER-1 is a Phase 2 study of CLR 131 being conducted in approximately 10 leading cancer centers in the United States in patients with relapsed or refractory B-cell hematologic cancers. The hematologic cancers being studied in the trial include multiple myeloma (MM), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL).

The study will enroll up to 80 patients. Its primary endpoint is clinical benefit response (CBR), with additional endpoints of overall response rate (ORR), progression free survival (PFS), median overall survival (OS) and other markers of efficacy following a fractionated dose of 37.575mCi/m2 of CLR 131 administered in two 30-minute infusions of 18.75mCi/m2 of CLR 131 administered on day 1 and day 8, with the option for a second dose cycle approximately 75-180 days later. The company expects to report topline data in 2019.

Cellectar was awarded approximately $2 million in non-dilutive grant funding from the National Cancer Institute to help fund the trial. More information about the trial, including eligibility requirements, can be found at www.clinicaltrials.gov, reference NCT02952508.

About CLR 131

CLR 131 is a small-molecule, cancer-targeting radiotherapeutic Phospholipid Drug ConjugateTM (PDC) designed to deliver cytotoxic radiation directly and selectively to cancer cells and cancer stem cells. CLR 131 is the company’s lead therapeutic PDC product candidate and is currently being evaluated in both Phase 2 and Phase 1 clinical studies. The FDA granted orphan drug designation for CLR 131 for the treatment of multiple myeloma as well as orphan drug and rare pediatric disease designations for CLR 131 for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. In addition to the ongoing Phase 1 dose-escalation study and the Phase 2 (CLOVER-1) trial, the company recently initiated a Phase 1 open-label, dose-escalating study in pediatric solid tumors and lymphoma to evaluate the safety and tolerability of a single intravenous administration of CLR 131 in up to 30 children and adolescents with cancers including neuroblastoma, sarcomas, lymphomas (including Hodgkin’s lymphoma) and malignant brain tumors.