On September 24, 2018 Protagonist Therapeutics, Inc. (NASDAQ:PTGX) reported that Dinesh V. Patel, Ph.D., President and Chief Executive Officer, will provide a corporate overview at the Cantor Fitzgerald Global Healthcare Conference at 4:40 p.m. at the InterContinental New York Barclay Hotel (Press release, Protagonist, SEP 24, 2018, View Source;p=RssLanding&cat=news&id=2368526 [SID1234529551]).

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Presentation details:

Event: Cantor Fitzgerald Global Healthcare Conference
Date: Monday, Oct. 1, 2018
Time: 4:40 p.m. EDT

A live and archived audio webcast of the presentation can be accessed by visiting the Investors page of the Protagonist Therapeutics website at View Source

On September 24, 2018 PharmaMar (MSE:PHM) reported that it has presented data during the International Association for the Study of Lung Cancer (IASLC 2018), that is taking place from the 23rd to the 26th of September in Toronto (Canada), on Overall Survival (OS) from the Phase I/II Study of lurbinectedin in combination with doxorubicin for relapsed small cell lung cancer (Press release, PharmaMar, SEP 24, 2018, View Source [SID1234529550]).

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An OS of 10.2 months has been observed in the study for patients treated with lurbinectedin in combination with doxorubicin in patients with a CTFI of 30 days or longer, reaching 11.5 months in platinum-sensitive patients (CTFI- equal or better than 90 days).

We believe that the OS periods observed in this trial are more favorable than those seen in historical trials of the primary treatments used for second line in SCLC, such as topotecan or the CAV combination (cyclophosphamide, adriamycin, vincristine).

This Phase I/II multicenter, clinical study has analyzed the second line treatment of patients with SCLC, corresponding to cohort B (n=27), of the study, involving a doses of 2mg/m2 of lurbinectedin + 40mg/m2 of doxorubicin, the same doses and similar population to that being evaluated in the randomized Phase III ATLANTIS Study. In July 2018 this study reached its recruitment objective of 600 patients from 160 centers in 20 countries, and the results are expected at the end of 2019. Dr. Martin Forster, MD, PhD, of the University College London Hospitals and UCL Cancer Institute, UK, has commented, "I have been involved in a wide number of trials with lurbinectedin for more than five years, both in studies as a single agent and in combination, and I think that it is a molecule with a novel mechanism of action and promising anti-cancer activity, which has exhibited acceptable safety profile both as a single agent and in combination. I consider lurbinectedin as an innovative molecule, which I think may have an important role to play in the treatment of patients with this particularly aggressive type of lung cancer, if approved."

Dr. Emiliano Calvo, MD, from the START Madrid-CIOCC Early Phase Clinical Drug Development program, at Hospital Universitario HM Sanchinarro, Madrid, Spain, has affirmed that "it is very necessary to have new alternatives for the treatment of this type of aggressive cancer. As we have been able to observe in the Overall Survival data, the combination of lurbinectedin plus doxorubicin appears to show a greater benefit than the current standard treatments, therefore, possibly providing a new therapeutic alternative for the patients that suffer this terrible illness." He adds, "patients with small cell lung cancer need new therapeutic alternatives, and the results of this lurbinectedin study could help change the landscape of treatment in an environment where, unfortunately, important progress has not been made within the last 15-20 years."

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On September 24, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) recording that updated phase 1 safety and efficacy data for [fam-] trastuzumab deruxtecan (DS-8201), an investigational HER2 targeting antibody drug conjugate (ADC), were presented for a subgroup of patients with heavily pretreated HER2 mutated or HER2 expressing non-small cell lung cancer (NSCLC) during an Oral Session at the IASLC 19th World Conference on Lung Cancer (#WCLC2018) hosted by the International Association for the Study of Lung Cancer in Toronto, Canada (Press release, Daiichi Sankyo, SEP 24, 2018, View Source [SID1234529547]).

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An updated subgroup analysis of 11 patients with HER2 mutated NSCLC receiving a recommended expansion dose of 6.4 mg/kg showed that [fam-] trastuzumab deruxtecan demonstrated a confirmed overall response rate of 72.7 percent (8 of 11 patients) and disease control rate of 100 percent (11 of 11 patients). Preliminary estimate of median duration of response has reached 11.5 months (95 percent CI: 0.03+, 11.5) and median progression-free survival has reached 14.1 months (95 percent CI: 4.0+, 14.1) for this subgroup of patients.

"These preliminary results seen with [fam-] trastuzumab deruxtecan are encouraging, particularly given the existing unmet medical need for patients with metastatic NSCLC with HER2 alterations that have progressed on several prior therapies," said Junji Tsurutani, MD, PhD, Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan, a study investigator. "These results also demonstrate that continued evaluation of treatments that target the HER2 receptor is warranted in patients with NSCLC."

The updated subgroup analysis of 17 patients with heavily pretreated HER2 mutated or HER2 expressing (defined as IHC ≥1+ or amplified) NSCLC showed that [fam-] trastuzumab deruxtecan demonstrated a confirmed overall response rate of 58.8 percent (10 of 17 patients) and a disease control rate of 88.2 percent (15 of 17 patients). Preliminary estimate of median duration of response has reached 9.9 months (95 percent CI: 0.0+, 11.5) and median progression-free survival has reached 14.1 months (95 percent CI: 0.9, 14.1).

"Patient enrollment is currently underway into our phase 2 study of [fam-] trastuzumab deruxtecan in patients with advanced HER2 mutated or HER2 overexpressing NSCLC," said Gilles Gallant, BPharm, PhD, Vice President, DS-8201 Global Team Leader, Oncology Research and Development, Daiichi Sankyo. "Since there are no therapies specifically approved to treat patients with HER2 altered NSCLC, continued study of [fam-] trastuzumab deruxtecan is needed to better understand the potential role of a HER2 targeting antibody drug conjugate in treating these patients."

Updated preliminary safety data for this subgroup of patients with heavily pretreated HER2 mutated or HER2 expressing NSCLC receiving [fam-] trastuzumab deruxtecan were also reported. The most common adverse events (>30 percent, any grade) included nausea (50.0 percent), decreased appetite (50.0 percent), alopecia (50.0 percent), fatigue (44.4 percent) and vomiting (38.9 percent). Grade 3 adverse events occurring in >10 percent of patients included decreased neutrophil count (11.1 percent). As previously reported, one (1) grade 5 event of pneumonitis was observed in this cohort, which was adjudicated as unrelated to [fam-] trastuzumab deruxtecan by an independent adjudication committee. Any reported cases of interstitial lung disease (ILD)/pneumonitis in the [fam-] trastuzumab deruxtecan clinical development program are evaluated by an independent adjudication committee.

Unmet Need in Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the most common cancer in the world and the leading cause of cancer deaths.1 There were approximately 1.8 million new cases of lung cancer reported globally and approximately 1.6 million deaths in 2012.1 Non-small cell lung cancer (NSCLC) accounts for approximately 80 to 85 percent of all cases.2 The five-year survival rate for metastatic NSCLC is only one percent.3

The introduction of targeted therapies and checkpoint inhibitors in recent years has improved the treatment landscape for metastatic NSCLC patients, who previously had limited options beyond systemic chemotherapy.4,5 However, for those who are not eligible for available treatments, or whose cancer continues to progress, new approaches are needed to help manage the disease.6

HER2 overexpression has been reported in rates ranging from 4 to 35 percent of NSCLC, depending on the published series and methods, and is associated with poor disease prognosis and shortened overall survival.4,6 HER2 mutations have more recently been identified as distinct molecular targets for NSCLC and have been reported in up to 5 percent of NSCLC.7,8 Currently, no therapy is specifically approved for HER2 mutated or HER2 overexpressing non-small cell lung cancer.

About the [Fam-] Trastuzumab Deruxtecan Phase 1 Study

An open-label, two-part phase 1 study is currently evaluating [fam-] trastuzumab deruxtecan in patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerant to standard treatment, or for whom no standard treatment is available. The primary objective of the dose escalation phase of this study was to assess the safety and tolerability of and determine the maximum tolerated dose. Data from this part of the study were published in the Lancet Oncology.9

In the dose expansion part of the phase 1 study, [fam-] trastuzumab deruxtecan is given in one of two doses (5.4 mg/kg and 6.4 mg/kg) to patients with HER2 positive advanced or metastatic breast cancer and gastric cancer, HER2 low expressing breast cancer and other HER2 expressing solid tumors including NSCLC. Overall, 292 patients have been enrolled into this phase 1 study of [fam-] trastuzumab deruxtecan. For more information about the study, visit ClinicalTrials.gov.

About [Fam-] Trastuzumab Deruxtecan

[Fam-] trastuzumab deruxtecan (DS-8201; [fam-] trastuzumab deruxtecan in U.S. only; trastuzumab deruxtecan in other regions of world) is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, [fam-] trastuzumab deruxtecan is comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

A broad and comprehensive development program with [fam-] trastuzumab deruxtecan is underway in North America, Europe and Asia. [Fam-] trastuzumab deruxtecan is in pivotal phase 2 clinical development for HER2 positive metastatic breast cancer resistant or refractory to ado-trastuzumab emtansine (DESTINY-Breast01); pivotal phase 2 development for HER2 positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01); phase 2 development for HER2 expressing advanced colorectal cancer; phase 2 development for metastatic non-squamous HER2 overexpressing or HER2 mutated NSCLC; and, phase 1 development in combination with nivolumab for HER2 expressing metastatic breast and bladder cancer.

[Fam-] trastuzumab deruxtecan has been granted Breakthrough Therapy designation for the treatment of patients with HER2 positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2 positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2 targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). [Fam-] trastuzumab deruxtecan has received SAKIGAKE Designation for the treatment of HER2 positive advanced gastric or gastroesophageal junction cancer by the Japan Ministry of Health, Labour and Welfare (MHLW).

[Fam-] trastuzumab deruxtecan is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise

The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in pivotal stage development include: [fam-] trastuzumab deruxtecan, an antibody drug conjugate (ADC) for HER2 expressing breast, gastric and other cancers; quizartinib, an oral selective FLT3 inhibitor, for newly-diagnosed and relapsed/refractory FLT3-ITD acute myeloid leukemia (AML); and pexidartinib, an oral CSF1R inhibitor, for tenosynovial giant cell tumor (TGCT). For more information, please visit: www.DSCancerEnterprise.com.

On September 24, 2018 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that the following presentations by Company management at upcoming investor conferences will be webcast (Press release, ImmunoGen, SEP 24, 2018, View Source [SID1234529543]):

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2018 Cantor Global Healthcare Conference
October 2 at 2:50pm ET
Leerink Partners Roundtable Series
October 3 at 9:30am ET
A webcast of each presentation will be accessible live through the "Investors" section of the Company’s website, www.immunogen.com; a replay will be available in the same location for approximately two weeks.

On September 24, 2018 TP Therapeutics, a privately held, clinical-stage biopharmaceutical company developing oncology therapies with a focus on addressing drug resistance, reported its updated interim data as of July 13, 2018 from its ongoing Phase 1/2 TRIDENT-1 study of Repotrectinib (TPX-0005) in ROS1 fusion-positive non-small-cell lung cancer (NSCLC) patients (Press release, TP Therapeutics, SEP 24, 2018, View Source [SID1234529542]).

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"Additional follow-up of patients treated with Repotrectinib continues to demonstrate a meaningful and durable clinical benefit, with potency against difficult mutations that often drive resistance to this class of therapeutics," said Alice Tsang Shaw, MD, PhD, Professor of Medicine, Harvard Medical School; Director of Thoracic Oncology, Massachusetts General Hospital; and an Investigator in the TRIDENT-1 study. "These early data, now supported by Blinded Independent Central Review, are encouraging in both TKI-naïve and TKI-pretreated NSCLC patients with the ROS1 fusion oncogene."

Repotrectinib is an investigational next-generation tyrosine kinase inhibitor (TKI) designed to effectively target ROS1, TRKA-C and ALK kinases, and also clinical resistance kinase domain mutations. ROS1 rearrangement is an oncogenic driver of tumors in up to 2.6 percent of U.S. NSCLC patients.

As of the July 13, 2018 data cut-off, the study findings showed:

A total of 72 patients (31 ALK+; 33 ROS1+; and 8 NTRK+ by local test) with advanced cancers had been treated across 6 dose levels (40 mg QD; 80 mg QD; 160 mg QD; 240 mg QD; 160 mg BID; and 200 mg BID), which comprises the safety population for the current dataset
A total of 30 patients treated across the first 5 dose escalation cohorts with ROS1+ NSCLC were in the efficacy evaluable population, of which 27 were evaluable by Blinded Independent Central Review (BICR)
Within the efficacy evaluable population of ROS1+ NSCLC, the median age was 52 years (range 30 – 75), with 53% of patients having CNS metastases at baseline; the median number of prior TKI therapies (majority of which were crizotinib) was 1 (range 0 to 3).
Preliminary Safety Analysis (n=72)

Repotrectinib was generally well tolerated, with the most frequent treatment-related adverse events (TRAEs >15%) including dizziness (50%); dysgeusia (45.8%); paraesthesia (29.2%); constipation (19.4%); and fatigue (18.1%); the majority of TRAEs are Grade 1-2, and the Grade 3 TRAEs include 2.8% dizziness and 4.2% anemia
The vast majority (31/36 cases, 86%) of dizziness were Grade 1 and there have been no cases of dizziness that have led to treatment discontinuation
As of the data cut-off date, there have been no Grade 4 TRAEs
Four dose-limiting toxicities (DLTs) were observed: Grade 2 or 3 dizziness (n=3: 2 at 160 mg BID; 1 at 240 mg QD) that resolved upon dose reduction; and Grade 3 dyspnea/hypoxia (n=1 at 160 mg BID) that resolved after study drug discontinuation
Neither the maximum tolerated dose (MTD) nor the recommended Phase 2 dose (RP2D) has been reached
Preliminary Efficacy Analysis (n=27)

As of the data cutoff, 27 ROS1+ NSCLC patients were evaluable for tumor response by BICR
Of the 27 patients, 10 were TKI-naïve and 17 were previously treated with at least one ROS1 TKI therapy
Fifteen of 27 patients (56%) remained on treatment
The primary reason for treatment discontinuation was progression (radiologic or clinical, n=9), with 1 patient each discontinuing for withdraw of consent, investigator decision, and adverse event (DLT of Grade 3 dyspnea/hypoxia at 160 mg BID)
TKI-Naïve Efficacy Analysis (n=10)

A confirmed overall response (ORR) by BICR analysis based on RECIST v1.1 was achieved in 8 of 10 patients (80%; CI 44-97), with a median time to response of 1.6 months (1.4-3.3). Confirmed responses were achieved across all 5 doses tested to date within dose escalation
The Intracranial ORR was 100 percent with 3 of 3 patients with measurable CNS disease achieving a confirmed response (CI 29-100). All 3 patients who achieved an intracranial response also achieved an extracranial response
The overall clinical benefit rate was 100 percent, with all 10 patients achieving stable disease for at least two cycles or a confirmed partial response
Of the 8 patients who achieved a confirmed response, 5 continue to maintain their response (3.7+ – 11.1+ months)
TKI-Pretreated Efficacy Analysis (n=17)

Across 5 dose escalation cohorts, a confirmed ORR was achieved in 3 patients (3/17, 18%; CI 4-44), with a median time to response of 1.6 months (1.5-1.8) with 2 of 3 responses occurring at the 160 mg QD dose level
All 3 responses were achieved in patients treated with 1 prior TKI (3/13, 23%) and duration of the responses were 11.1+ months; 7.4 months; and 1 patient who was censored at the time of their last tumor assessment as they withdrew consent while remaining in response
Intracranial ORR was achieved in 1 of 4 patients (25%)
Of importance, the overall clinical benefit rate was 76 percent (95% CI: 56-97) with 13 of 17 patients achieving stable disease for at least 2 cycles or a confirmed partial response
With respect to baseline plasma cell-free DNA (cfDNA), 16 of 17 TKI-pretreated patients had plasma samples evaluated at baseline
Four crizotinib-pretreated patients were identified as having a ROS1 solvent front G2032R mutation at baseline. All 4 patients had tumor regressions on Repotrectinib including 1 confirmed partial response of 7.4 months achieved at the 160 mg QD dose level. This patient remained on treatment for 11+ months at the time of the data cut-off.
"We are very pleased with the updated Phase 1 preliminary data, which continue to demonstrate the strong activity of Repotrectinib in both TKI-naïve and TKI-pretreated patients with ROS1+ NSCLC since our initial data presentation in June," said Athena Countouriotis, M.D., Executive Vice President and Chief Medical Officer of TP Therapeutics. "We continue to enroll patients in additional dosing cohorts, and look forward to determining the recommended Phase 2 dose and discussing our path to registration with health authorities. We plan to begin the Phase 2 portion of the TRIDENT-1 study as soon as a RP2D is identified with the goal of bringing a potential new treatment option to patients in this area of high unmet need."

The data were presented earlier today by Jessica J. Lin, M.D., Massachusetts General Hospital Cancer Center, in an oral presentation at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer in Toronto.

Initial preliminary data from the ongoing Phase 1 portion of the TRIDENT-1 study were presented in June 2018 at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper). In addition, the preclinical and clinical proof-of-concept data for Repotrectinib were recently published in the journal Cancer Discovery (The Cancer Discovery article may be found online at: View Source).

About Repotrectinib (TPX-0005)

Repotrectinib (TPX-0005) is a potent and orally bioavailable investigational small molecule kinase inhibitor for ALK, ROS1, and TRK family. The clinical benefits of targeting ALK, ROS1, or TRK fusion kinase have been demonstrated with multiple kinase inhibitors already approved for the treatment of ALK+ non-small cell lung cancer (NSCLC), in addition to crizotinib for ROS1+ NSCLC, and larotrectinib and entrectinib in clinical studies for TRK+ cancers. The successes of these therapies are overshadowed by the development of acquired resistance. The acquired solvent front mutations including ALK G1202R, ROS1 G2032R, TRKA G595R and TRKC G623R render a common clinical resistance to the current ALK, ROS1, and TRK inhibitors.

Repotrectinib has demonstrated potency against wildtype and mutated ALK, ROS1 and TRK family kinases, especially the clinically significant solvent front mutations, gatekeeper mutations, and emerging compound mutations after multiple line treatments. Repotrectinib may provide a new opportunity to inhibit the abnormal signaling of ALK, ROS1, or TRK family in solid malignancies, and overcome multiple resistance mechanisms seen in refractory patients. Repotrectinib is currently being evaluated in a Phase 1/2, open-label, multi-center, first-in-human study of the safety, tolerability, pharmacokinetics and anti-tumor activity in patients with advanced solid tumors harboring ALK, ROS1, or NTRK1-3 rearrangements TRIDENT-1 study (www.clinicaltrial.gov number NCT03093116). Interested patients and physicians can also contact the TP Therapeutics Oncology Clinical Trial Hotline at 1-858-276-0005 or email [email protected].

1Note: TPX-0005 had an initial generic name of "ropotrectinib," which was later changed to repotrectinib and is now the accepted name by USAN and WHO INN.