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 [SID1234539912]).

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"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 CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a clinical-stage biopharmaceutical company focused on developing and providing access to innovative therapies for patients with liver and other chronic diseases with high unmet medical need, reported that management will present a corporate overview at the 2019 Cantor Global Healthcare Conference, taking place October 2-4, 2019 in New York City (Press release, CymaBay Therapeutics, SEP 30, 2019, View Source [SID1234539911]).

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2019 Cantor Global Healthcare Conference
Date: Thursday, October 3
Time: 9:30am Eastern Time
Webcast: View Source

On September 30, 2019 Checkpoint Therapeutics, Inc. ("Checkpoint") (NASDAQ: CKPT), a clinical-stage immuno-oncology biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for patients with solid tumor cancers, reported that positive interim results for cosibelimab, a potentially differentiated high affinity anti-PD-L1 antibody with functional Fc domain, were presented on Saturday, September 28th, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2019 in Barcelona, Spain (Press release, Checkpoint Therapeutics, SEP 30, 2019, View Source [SID1234539910]). The poster presentation provided updated interim efficacy and safety results from Checkpoint’s ongoing multicenter Phase 1 clinical trial, including expansion cohorts in cutaneous squamous cell carcinoma ("CSCC") and non-small cell lung cancer ("NSCLC"). Checkpoint continues to enroll CSCC patients to support an initial Biologics License Application ("BLA") submission for cosibelimab based on this ongoing clinical trial.

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"The compelling data presented at the ESMO (Free ESMO Whitepaper) Congress demonstrate strong and durable efficacy in CSCC and NSCLC and a potentially favorable safety profile as compared to the class of anti-PD-1 antibodies currently available," said James F. Oliviero, President and Chief Executive Officer of Checkpoint Therapeutics. "As the second deadliest skin cancer after melanoma, it is estimated that CSCC is responsible for approximately 7,000 deaths each year in the United States. We are confident that cosibelimab could soon provide CSCC patients with a highly effective and better tolerated treatment option as compared to the single anti-PD-1 therapy on the market today. With 25 CSCC patients enrolled to date, we intend to fully enroll the CSCC cohort in 2020 to potentially support an initial BLA filing, with the goal of positioning cosibelimab as a differentiated and lower-cost alternative to the approved therapy available today."

Summary of Interim Clinical Results

The Phase 1, open-label, multicenter trial (NCT03212404) is evaluating the safety, efficacy and pharmacokinetics of cosibelimab in checkpoint therapy-naïve patients with selected recurrent or metastatic cancers. Following dose escalation, the trial initiated multiple disease-specific expansion cohorts, including in CSCC and NSCLC, evaluating a fixed dose of 800 mg cosibelimab dosed intravenously every two weeks. As of August 5, 2019, 81 patients with diverse tumor types have been treated with cosibelimab.

Sixty-eight patients were evaluable for efficacy at the time of data cutoff, having at least two tumor assessments or discontinued treatment prior. Key efficacy results were as follows:

50% objective response rate ("ORR") in CSCC patients per RECIST v1.1. One patient achieved a complete response and six patients achieved partial responses. All seven responses (100%) are confirmed and ongoing with the longest duration at 11.4 months at the time of analysis.

40% ORR in first-line NSCLC patients with high (≥50%) expression of PD-L1 per RECIST v1.1. Ten patients achieved partial responses (eight confirmed and two pending confirmation). Nine of 10 responses (90%) are ongoing with the longest duration at 11 months at the time of analysis.
The best overall tumor response is shown below for all tumor types and the subgroup cohorts of CSCC and NSCLC.

Best Overall Tumor Response
by RECIST v1.1 All Tumor Types (n=68) CSCC
(n=14) NSCLC
(n=25)
Complete response, n (%) 1 (1.5) 1 (7.1) 0 (0.0)
Partial response, n (%) 18 (26.4) 6 (42.9) 10 (40.0)
Stable disease, n (%) 20 (29.4) 2 (14.3) 9 (36.0)
Progressive disease, n (%) 14 (20.6) 2 (14.3) 2 (8.0)
Not evaluated/done, n (%) 15 (22.1) 3 (21.4) 4 (16.0)
Overall response rate, % (95% CI) 27.9 (17.7, 40.1) 50.0 (23.0, 77.0) 40.0 (21.1, 61.3)
Response ongoing, n (%) 17/19 (89.5) 7/7 (100.0) 9/10 (90.0)
Median duration of response, months (min, max) Not reached
(0.1, 11.4) Not reached
(2.5, 11.4) Not reached
(0.1, 11.0)
Disease control rate, % 57.3 64.2 76.0
Objective response rate = best overall response of complete response or partial response divided by the number of evaluable patients; disease control rate = best overall response of complete response, partial response, or stable disease divided by the number of evaluable patients.

Cosibelimab appeared to be safe and well-tolerated with a potentially favorable safety profile as compared to the currently available anti-PD-1 therapies. Treatment‐related adverse events ("AEs") occurred in 48/81 (59%) patients, most commonly rash (n=11, 13.6%), fatigue (n=8, 9.9%), hypothyroidism (n=7, 8.6%), anemia (n=6, 7.4%), alanine aminotransferase increase, diarrhea, and infusion-related reaction (n=5, 6.2% each). Treatment‐related grade ≥3 AEs occurred in 5/81 (6%) patients, with only two patients (2.5%) discontinuing treatment due to a treatment-related AE.

A copy of the poster presentation is available on the Publications page of the Pipeline section of Checkpoint’s website, www.checkpointtx.com.

Additional information on the meeting can be found on the ESMO (Free ESMO Whitepaper) website, www.esmo.org.

About Cutaneous Squamous Cell Carcinoma
Cutaneous squamous cell carcinoma ("CSCC") is the second most common human cancer in the United States, with an estimated annual incidence of 700,000 cases. While most cases are localized tumors amenable to curative resection, approximately 8% of patients will experience a local recurrence, 5% of patients will develop nodal metastases, and an estimated 2% of patients will die from their disease. Ten-year survival rates are less than 20% for patients with regional lymph-node involvement. For those patients who develop distant metastases, the median survival time is estimated to be less than two years. In addition to being a life-threatening disease, CSCC causes significant functional morbidities and cosmetic deformities based on tumors commonly arising in the head and neck region and invading blood vessels, nerves and vital organs such as the eye or ear.

About Cosibelimab
Cosibelimab (formerly referred to as CK-301) is a high affinity, fully-human monoclonal antibody of IgG1 subtype that directly binds to programmed death ligand-1 (PD-L1) and blocks the PD-L1 interaction with the programmed death receptor-1 (PD-1) and B7.1 receptors. PD-L1 is an immune-inhibitory checkpoint molecule expressed on epithelial and vascular endothelial cells, as well as by a number of immune cells, and is utilized by tumor cells as an immune escape mechanism. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response. Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies with a half-life that supports sustained >99% target tumor occupancy and the additional benefit of a functional Fc domain capable of inducing antibody-dependent cell-mediated cytotoxicity ("ADCC") for potential enhanced efficacy in certain tumor types.

On September 30, 2019 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported updated data from patients with synovial sarcoma who were treated in the ongoing Phase 1 trial with SPEAR T-cells targeting MAGE-A4 (ADP-A2M4) (Press release, Adaptimmune, SEP 30, 2019, View Source [SID1234539909]). The oral presentation by Brian Van Tine, MD, PhD of Washington University in St. Louis, occurred earlier today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Barcelona, Spain.

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"These data demonstrate a clear benefit of SPEAR T-cells for this population of patients with synovial sarcoma. These results are truly meaningful in this rare and deadly disease because patients with advanced synovial sarcoma have very few treatment options," said Elliot Norry, Adaptimmune’s interim Chief Medical Officer. "These data and the recent FDA orphan drug designation for ADP-A2M4 in sarcoma are important positive steps to expedite further development. We recently started SPEARHEAD-1, our Phase 2 trial in synovial sarcoma and myxoid/round cell liposarcoma (MRCLS), with the aim to commercialize ADP-A2M4 in 2022."

Overview of data presented at ESMO (Free ESMO Whitepaper)

This is a Phase 1 dose escalation, multi-tumor trial to assess the safety, tolerability, and antitumor activity of ADP-A2M4 in HLA-A2+ patients. As of Sep. 03, 2019, data from 12 patients with synovial sarcoma treated in the expansion phase of this trial demonstrated a best overall response rate of 58% (including both confirmed and unconfirmed partial responses [PRs]). There was a disease control rate of 92%, defined as objective overall response (including confirmed and unconfirmed PRs) and stable disease.

Most adverse events were consistent with those typically experienced by cancer patients undergoing cytotoxic chemotherapy or other cancer immunotherapies. Fatal aplastic anemia was reported in 1 patient with synovial sarcoma in this trial. This event was previously described and reported to the US Food and Drug Administration.

The median age of these patients was 54 years and they had received a median of 2 prior lines of systemic therapy. The median dose received was 9.7 billion SPEAR T-cells (range 3.4 to 10 billion transduced cells).

Data from patients with synovial sarcoma treated in the expansion phase of this trial were previously reported in May of this year. At that time 8 patients had been assessed, with 6 showing a decrease in tumor size, of which 3 patients had confirmed partial responses and 1 patient had an unconfirmed partial response.

Detailed summary of response data presented at ESMO (Free ESMO Whitepaper) for ADP-A2M4 in patients with synovial sarcoma

Twelve patients received treatment in the expansion phase of this trial and had post-baseline scans to assess efficacy by time of data cutoff (Sep. 03, 2019).

·Of the 12 patients with post-baseline scans to assess efficacy:
o11/12 showed clinical benefit with best overall responses of PR (confirmed or unconfirmed; n=7) or stable disease (SD; n=4); this represents a disease control rate of 92%
o7/12 had clinical responses representing a best overall response rate of 58% with
§5 confirmed PRs (cPR) by RECIST criteria; 3 of which remain ongoing at the time of data cutoff; 2 of which developed progressive disease (PD)
§ unconfirmed PRs (ucPR) that remain ongoing at the time of data cutoff
·Higher peak SPEAR T-cell expansion was associated with decreases in target lesions from baseline

About Adaptimmune’s ADP-A2M4 program in sarcoma

Adaptimmune’s ADP-A2M4 SPEAR T-cell therapy is directed to a member of the MAGE family of cancer testis antigens (MAGE-A4) expressed in a number of solid tumor cell types. The MAGE- A4 antigen is among the most commonly expressed cancer testis antigens. Adaptimmune is evaluating ADP-A2M4 in synovial sarcoma and MRCLS in a number of trials including the recently initiated Phase 2 trial SPEARHEAD-1 in sarcoma, as well as the ongoing Phase 1 trial, which includes a radiation sub-study to enhance T-cell trafficking and antitumor activity. Both the radiation sub-study and Phase 1 trial include sarcoma as well as multiple other solid tumor indications. Adaptimmune is also evaluating a next-generation SPEAR T-cell (ADP-A2M4CD8) targeting MAGE-A4 in sarcoma as well as other solid tumor indications in the SURPASS trial.

On September 30, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported that it will be attending the 2019 Cell & Gene Meeting on the Mesa being held October 2nd – October 4th in Carlsbad, CA (Press release, Actinium Pharmaceuticals, SEP 30, 2019, View Source [SID1234539908]). Members of Actinium’s executive and R&D teams will highlight the Iomab-ACT program at the meeting. To schedule a meeting with Actinium please email Eileen Geoghegan, Ph.D., at [email protected] or through the meeting’s partnering system View Source

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Actinium is developing its Iomab-ACT program to be a universal lymphodepletion regimen to replace chemotherapy-based regimens such as Flu/Cy (Fludarabine and Cyclophosphamide) that are used in standard practice today. Actinium proposes that Iomab-ACT has a multi-modal mechanism of action that can; 1) deplete lymphocytes to create a suitable homeostatic cytokine environment; 2) deplete immune suppressive cell populations that may hinder activation of CAR-T cells; (3) deplete macrophages that may secrete cytokines implicated in CRS and neurotoxicity; and (4) potential anti-tumor effect on CD45+ blood cancer cells.

Iomab-ACT is an ARC or Antibody Radiation-Conjugate that targets the antigen CD45, which is uniquely expressed on leukemia, lymphoma and immune cells making it an ideal target for targeted condition prior to CAR-T and adoptive cell therapies. Iomab-ACT is a lower, outpatient, non-myeloablative dose of Actinium’s lead program, Iomab-B, which has been studied in over 300 patients and is currently being studied as a targeted conditioning agent prior to bone marrow transplant in a pivotal Phase 3 trial.

Actinium presented initial feasibility data for its ACT program at the Transplantation and Cellular Therapies Meeting in February 2019. The data demonstrated that a CD45 targeting antibody labeled with the radioisotope Iodine-131 effectively depleted greater than 90% of lymphocytes and other immune cells while sparing platelets, neutrophils and bone marrow stem cells in preclinical animal models (Click here for TCT poster). Additionally, in a preclinical model of adoptive cell therapy, the CD45-targeted ARC enabled improved tumor control. Actinium also presented data at the Society of Nuclear Medicine and Molecular Imaging demonstrating that the Iomab-ACT program could utilize the radioisotope Lutetium-177 with an anti-CD45 antibody to achieve targeted lymphodepletion prior to adoptive cell therapy (Click here for SNMMI poster).

About the Cell & Gene Meeting on the Mesa

The Cell & Gene Meeting on the Mesa is the sector’s foremost annual conference bringing together senior executives and top decision-makers in the industry to advance cutting-edge research into cures. Tackling the commercialization hurdles facing the cell and gene therapy sector today, this meeting covers a wide range of topics from clinical trial design to alternative payment models to scale-up and supply chain platforms for advanced therapies. The program features expert-led panels, extensive partnering capabilities, exclusive networking opportunities, and 70+ dedicated presentations by the leading publicly traded and privately held companies in the space. Attracting over 1,150 attendees – over 20% of which are C-level executives – this conference enables key partnerships through more than 2,200 one-on-one meetings while highlighting the significant clinical and commercial progress in the field.