On May 29, 2020 Xspray Pharma AB (Nasdaq Stockholm: XSPRAY) reported the start of the pivotal clinical bioequivalence studies with HyNap-Dasa. The studies are conducted on healthy volunteers with the objective to demonstrate that HyNap-Dasa is bioequivalent to the original drug Sprycel (dasatinib) (Press release, Xspray, MAY 29, 2020, View Source [SID1234649568]).

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The bioequivalence studies consist of two studies, where the first one, starting today, is conducted on fasted healthy volunteers. The second study, starting next month, is conducted on non-fasted healthy volunteers. In both studies, HyNap-Dasa bioavailability is compared to the original drug Sprycel. The preliminary results from the two studies are expected during the third quarter 2020.

"The initiation of the pivotal clinical trials marks a major milestone for Xspray and for our HyNap-Dasa product candidate," says Per Andersson, CEO Xspray. "HyNap-Dasa has in previous clinical studies shown positive results and we now look forward to see the clinical outcome this time as well, and take a big step closer to submitting our first application for market approval in the US."

The results of the two clinical trials together with the results of the ongoing stability studies will form the basis of the company’s ANDA application for market approval in the USA.

On May 29, 2020 BridgeBio Pharma, Inc. (Nasdaq: BBIO) affiliate QED Therapeutics reported that it will present data at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program showing clinical advancement for infigratinib, QED’s oral FGFR1-3 inhibitor, in both urothelial carcinoma and cholangiocarcinoma (CCA) (Press release, BridgeBio, MAY 29, 2020, View Source [SID1234576229]).

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Title: Infigratinib (BGJ398) in advanced/unresectable or metastatic urothelial carcinoma demonstrates consistent treatment response in both first-line and later-line treatment settings

Abstract: 5038

Presenter: Yung Lyou, City of Hope Comprehensive Cancer Center

An analysis of response rates in patients with advanced/unresectable or metastatic urothelial carcinoma based on the amount of prior lines of treatment showed consistent response to infigratinib. The objective response rate (ORR) for all patients (n=67) was 25% (95% CI 15.5-37.5), while the ORR for patients receiving infigratinib as first-line treatment (n=13) saw a response rate of 31% (95% CI 9.1-61.4) compared to 24% (95% CI 13.5-37.6) for patients receiving infigratinib as a second-line or later treatment (n=54). All eight patients in the study with upper tract urothelial carcinoma (UTUC) received infigratinib as second-line or later therapy. The response rates were higher for patients with UTUC, with an ORR of 50% (95% CI 15.7–84.3) and a disease control rate of 100%. In the study, treatment emergent adverse events occurring in >30% of patients were: hyperphosphatemia (46%), elevated creatinine (42%), fatigue (37%), constipation (37%), anemia (36%), decreased appetite (33%), dry mouth (31%), and alopecia (31%).

"These findings support the design of the ongoing, placebo-controlled PROOF 302 study to evaluate the efficacy of infigratinib in adjuvant urothelial carcinoma," said author and PROOF 302 trial lead Sumanta Pal, MD, professor of medical oncology and therapeutics research at City of Hope Comprehensive Cancer Center. "The results in upper tract urothelial cancer (UTUC) build upon earlier research that the disease has a different genetic profile than urothelial carcinoma of the bladder, particularly with respect to FGFR3 alterations, and warrants further investigation in an even earlier setting."

Title: A retrospective analysis of post second-line chemotherapy treatment outcomes for patients with advanced or metastatic cholangiocarcinoma and FGFR2 fusions

Abstract: 4591

Presenter: Milind M. Javle, MD Anderson Cancer Center

In a retrospective analysis of a subset of a single-arm Phase 2 study of infigratinib (n=37), outcomes from patients with FGFR-fusion-positive bile duct cancer receiving infigratinib as third- and later-line therapy were compared with the tumor response when those same patients received second-line therapy with chemotherapy. Treatment with infigratinib resulted in progression free survival (PFS) improvements. The median PFS was 6.8 months (95% CI 3.9-7.8 months) for third- and later-line infigratinib treatment compared to 4.6 months (95% CI 2.7-7.2 months) for second-line chemotherapy.

"Through this retrospective analysis, we can see that infigratinib may have potential for patients whose tumors progress after second-line chemotherapy," said Susan Moran, MD, MSCE, chief medical officer for QED. "These data support continued investigation of infigratinib in patients with FGFR-driven cholangiocarcinoma."

On May 29, 2020 Athenex, Inc. (Nasdaq: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer, reportted interim data from an ongoing Phase II clinical trial in which oral paclitaxel and encequidar ("Oral Paclitaxel", formerly known as Oraxol) monotherapy showed encouraging efficacy and tolerability in elderly patients with unresectable cutaneous angiosarcoma, an aggressive malignancy with poor prognosis (Press release, Athenex, MAY 29, 2020, View Source [SID1234573876]). The interim results are being presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 (ASCO20) Virtual Scientific Program, being held from May 29 to 31, 2020, and reflect data from 22 evaluable patients out of 26 enrolled patients (16 males and 10 females, median age 75 years (range: 49-93 years)).

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The interim data showed a clinical benefit rate (CR+PR+SD) of 100% in 22 evaluable patients receiving Oral Paclitaxel treatment, who reached their first post treatment efficacy evaluation. All 22 patients experienced reduction in tumor size. Complete responses (CR) were observed in 27.3% of patients (6/22), partial responses (PR) were observed in 22.7% of patients (5/22), and stable disease was observed in 50% of patients (11/22). Oral Paclitaxel has been generally well tolerated in this predominantly elderly population.

"The responses to Oral Paclitaxel observed thus far are very encouraging, especially given the highly aggressive nature of cutaneous angiosarcoma and the lack of approved treatment options for this disease," said lead investigator Vinod Ravi, MD, MBA, associate professor in the Department of Sarcoma Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas. "Oral Paclitaxel appears to be well tolerated, even in older patients. We look forward to continue advancing the study, which will allow us to further characterize this potentially valuable treatment option for angiosarcoma."

Dr. Rudolf Kwan, Chief Medical Officer of Athenex, commented, "The interim data in this Phase II trial add to the growing body of evidence supporting the potential broad clinical utility of Oral Paclitaxel, which has already shown strong clinical data in a Phase III pivotal trial in patients with metastatic breast cancer."

The interim Phase II data, presented as Poster #11517 A Phase II Study of Oral Paclitaxel with Encequidar in the Treatment of Unresectable Cutaneous Angiosarcoma will be part of the Sarcoma Highlights Session on Sunday, May 31 at 3:30pm ET, at the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program. A copy of the poster presentation is available on Athenex’s website here.

About the Phase II Study of Oral Paclitaxel in Angiosarcoma

This single-arm Phase II study evaluates the activity, safety and tolerability of Oral Paclitaxel administered once daily for three consecutive days per week in patients with unresectable cutaneous angiosarcoma. Enrollment is ongoing at sites in the U.S., United Kingdom, Hong Kong and Taiwan, with a planned total enrollment of 43 subjects. For more information, refer to ClinicalTrials.gov Identifier: NCT03544567.

In April 2018, the U.S. Food and Drug Administration granted an Orphan Drug Designation for Oral Paclitaxel for the treatment of angiosarcoma. In addition, in October 2019, the Company received Orphan Designations from the European Commission for oral paclitaxel and encequidar for the treatment of soft tissue sarcoma.

The Orascovery platform, based on P-gp pump inhibition technology, was initially developed by Hanmi Pharmaceuticals and licensed exclusively to Athenex for all major worldwide territories except Korea, which is retained by Hanmi.

On May 29, 2019 Sihuan Pharmaceutical Holdings Group Ltd. (HKEx: 0460), the largest cardio-cerebral vascular ("CCV") drug manufacturer in China’s prescription drug market, reported the third generation of EGFR inhibitor XZP-5809, a Category 1 innovative drug developed by the Group, has been granted drug clinical trial approval by the National Medical Products Administration of the PRC (Press release, Sihuan Pharmaceutical, MAY 29, 2019, View Source [SID1234570979]).. The New Drug is a Category 1 innovative drug of the PRC developed by the Group .

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The New Drug is a novel third-generation epithelial growth factor receptor-tyrosine kinase inhibitor (”EGFR-TKI”) that has strong targeting capability, and can be taken orally. It features innovative structure, established mechanism and irreversible binding to EGFR. The New Drug has better selection with higher activity against gene-mutation EGFR and lower activity against wild-type EGFR.

Compared with products of the same type, the New Drug has distinct advantages in its activity and safety, based on the data collected from the completed preclinical trial. The New Drug and its metabolite have demonstrated lower activity against wild-type EGFR. With its better safety profile and global competitive advantage, the New Drug will be considered as a new treatment option for cancer patients.

Dr. Che Fengsheng, Chairman and CEO of Sihuan Pharmaceutical, said, "Significant progress has been made in the field of lung cancer treatment, including anti-cancer immunotherapy, but targeted therapy is still considered the best choice for non-small cell lung cancer (‘NSCLC’) with EGFR mutation."

The preclinical pharmacodynamic data and toxicological data indicate that the New Drug has the following characteristics: good efficacy against EGFR sensitive mutations (exon 19 deletion and L858R mutation) and against acquired resistance mutations (T790M mutation); potential clinical efficacy for patients with lung cancer brain metastasis; better safety profile and less impact on cardiac function when compared with drugs of the same type on the market. The clinical indication for the New Drug candidate is potential to be solid tumors such as locally advanced or metastatic lung cancer with EGFR-sensitive mutations (exon 19 deletion and L858R mutation) and acquired resistance mutations (T790M mutation).

Dr. Che stated, "The Group is committed to the fundamental research of innovative drugs, and finally obtains the clinical trial approval of the New Drug by overcoming the technical difficulties encountered. The obtained clinical trial approval for the New Drug will further enrich the Group’s product line layout in innovative drugs. In addition to the New Drug, the Group currently has Janagliflozin, an innovative drug in the field of anti-diabetes and a number of small molecule targeted innovative drugs such as Birociclib in the field of anti-tumor are in clinical trials and are making progress well. The layout of innovative drugs in various therapeutic fields has established a solid foundation for the Group’s research and development platform of innovative drugs."

Lung cancer is one of the malignant tumors with the highest morbidity and mortality in the world. In 2018, the number of cases of lung cancer around the world was 2.093 million. According to the cancer report statistics of the PRC, in terms of the number of cases, lung cancer ranks the first in the incidence of malignant tumors with approximately 781 thousand as the annual incidence cases number. According to the World Health Organization’s forecast, the number of lung cancer deaths in the PRC will exceed 1 million each year by 2025.

On May 29, 2020 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported at the ASCO (Free ASCO Whitepaper) Annual Meeting presented a preclinical update for its novel, clinical-stage, selective RET-inhibitor drug candidate, TPX-0046 (Press release, Turning Point Therapeutics, MAY 29, 2020, View Source [SID1234564371]).

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In the updated preclinical studies comparing proxy molecules for approved and investigational RET inhibitors, TPX-0046 demonstrated potent in vitro and in vivo activity against a range of RET alterations, including greater potency against solvent-front mutations, G810S, G810R, G810C and G810N.

A phase 1/2 trial of TPX-0046 in RET TKI-naïve and -pretreated patients is ongoing.

"TPX-0046 was designed as a potent RET inhibitor with the potential to address TKI-naïve and RET inhibitor-resistant RET-dependent cancers," said Alexander Drilon, M.D., medical oncologist and acting chief of the Early Drug Development Service, Memorial Sloan Kettering Cancer Center, and a principal investigator for the TPX-0046 clinical study. "Specifically, in preclinical studies, TPX-0046 inhibited RET solvent front mutations that have been observed in biopsies from patients with progression on a prior RET inhibitor. Developing a next-generation RET inhibitor is an unmet need."

In enzymatic and cellular assays presented at ASCO (Free ASCO Whitepaper), TPX-0046 was potent against wildtype RET and multiple RET mutations and fusions.TPX-0046 also demonstrated antitumor activity in RET-driven cell-derived and patient-derived xenograft tumor models, including those that harbor a RET G810R solvent-front mutation.

The ongoing Phase 1/2 open-label, single-arm, multi-center clinical study of TPX-0046 is enrolling TKI-naïve and -pretreated patients with RET-altered non-small-cell lung, thyroid, and other advanced cancers in a Phase 1 dose escalation study of approximately 50 patients, and Phase 2 expansion study of approximately 300 patients with multiple cohorts, to assess safety, tolerability, pharmacokinetics (PK) and clinical activity. The study design allows intra-patient dose escalation based on tolerability. For more information, visit clinicaltrials.gov and search NCT04161391.

"The preclinical studies we are presenting today support a potential role for TPX-0046 in both TKI-naïve and TKI-pretreated patients," said Athena Countouriotis, M.D., president and chief executive officer of Turning Point Therapeutics. "With a compact design, and lower molecular weight than other investigational or approved RET inhibitors, TPX-0046 has shown encouraging preclinical activity against multiple RET G810 mutations, where there are currently no approved therapeutic options for patients."

TPX-0046 is a multi-targeted RET and SRC kinase inhibitor with a novel three-dimensional macrocyclic structure that is smaller and structurally distinguished from other approved or investigational RET inhibitors. Activation of RET– a receptor tyrosine kinase –through gain-of-function mutations or fusions has been found in multiple tumor types, including non-small-cell lung and thyroid cancers. In preclinical studies TPX-0046 spared vascular endothelial growth factor (VEGF) receptors 1, 2 and 3. According to research published in the European Journal of Cancer1, hypertension was the most common adverse effect (up to 46 percent) among multiple anti-cancer therapeutics that inhibit VEGF. Dual inhibition of RET and SRC represents a novel therapeutic strategy to target abnormal RET signaling in cancers. Inhibition of SRC family kinases has the potential to reduce bypass resistance from signaling through multiple receptor tyrosine kinases and therefore has the potential to increase the therapeutic effect of TPX-0046.