On June 3, 2019 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops and commercializes high quality medicines, reported that the preliminary results of efficacy and safety of sintilimab, the anti-PD-1 antibody that co-developed with Eli Lilly and Company, in combination with CAPOX in first-line gastric or gastroesophageal junction carcinoma (GC/GEJC) (NCT02937116, cohort F) were presented by poster at the 55th annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) [Abstract #4042; Monday, June 3, 8:00 AM -11:00 AM CDT] (Press release, Innovent Biologics, JUN 3, 2019, View Source [SID1234536845]).

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As the top and most influential international oncology conference, ASCO (Free ASCO Whitepaper) Annual Meeting provides the most important platform for publishing and discussing cutting edge clinical studies. Under the theme "Caring for Every Patient, Learning from Every Patient," 2019 ASCO (Free ASCO Whitepaper) Annual Meeting has attracted numerous top oncologists, scholars, staff from regulatory and patient organizations to share the latest updates and achievements in clinical oncology, with the ultimate goal to help deliver more promising medicines and treatment options to cancer patients.

It is worth noting that more and more Chinese companies choose to participate and disclose their programs in ASCO (Free ASCO Whitepaper), showcasing the importance of emerging Chinese biotech industry. As a leading Chinese biotech company, Innovent will provide key result update of several clinical studies at the ASCO (Free ASCO Whitepaper) 2019 Annual Meeting. The results on the treatment of relapsed or refractory extranodal NK/T cell lymphoma (ORIENT-4) with sintilimab will be presented in an oral session, and key data from several other clinical studies will be presented by posters and other sessions.

Gastric cancer is the second most common malignant tumor in China. The development of new agents for the treatment of advanced gastric cancer has been stagnant and unmet clinical need is high. NCT02937116 is an open-label, multicenter, Phase Ib study in China. Cohort F of the study contains 20 patients, designed to evaluate the efficacy and safety of sintilimab in combination with CAPOX for GC/GEJC in the first-line setting.

At the data cutoff (15 Jan 2019), the median follow up was 5.8 months (range, 2.4 to 12.5).

The objective response rate (ORR) was 85.0% (95% CI, 62.1 to 96.8).
The disease control rate (DCR) was 100.0% (95% CI, 83.2 to 100.0).
The median duration of response (DOR) was 5.3 months (95% CI, 4.8 to 7.2) and median progression free survival (PFS) was 7.5 months (6.2-9.4). Sintilimab showed an acceptable safety profile during the study.
"Over the past decade, the treatment of various malignant tumors has progressed rapidly. From traditional chemotherapy to targeted molecular therapy and immunotherapy, the prognosis of cancer patients has been improved remarkably. However, breakthroughs in the treatment of gastric cancer have been few. The efficacy data in Phase Ib study of sintilimab in gastric cancer is encouraging. We hope to see more positive data in the phase III study and provide more effective treatments for patients through our efforts," said Professor Nong Xu, Director of the Department of Oncology of the First Affiliated Hospital of Zhejiang University.

About Tyvyt (sintilimab injection)

Tyvyt (sintilimab injection) is an innovative drug jointly developed in China by Innovent and Eli Lilly and Company. Innovent is also conducting clinical studies of sintilimab injection in the United States. Tyvyt (sintilimab injection) is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1/ PD-1 Ligand-1 (PD-L1) pathway and reactivates T-cells to kill cancer cells. Tyvyt (sintilimab injection) is the only PD-1 antibody in China branded by both a local biopharmaceutical company and a global pharmaceutical company. Tyvyt (sintilimab injection) has been granted marketing approval by the National Medical Products Administration (NMPA) for relapsed or refractory classical Hodgkin’s lymphoma (r/r cHL) and has been included in the 2019 Guidelines of Chinese Society of Clinical Oncology (CSCO) for Lymphoid Malignancies. There are currently more than twenty clinical studies using sintilimab injection, including eight registration studies that evaluate the efficacy of sintilimab injection in other solid tumors.

On June 3, 2019 ImmunityBio , a privately held immunotherapy company at late stage clinical development, that aims to synergistically deploy a broad portfolio of biological molecules as an integrated cancer vaccine platform targeting multiple tumor types without the use of high-dose chemotherapy, reported that Dr. Patrick Soon-Shiong will be presenting at the Jefferies 2019 Annual Healthcare Conference being held in New York City from June 4th-7th 2019 (Press release, ImmunityBio, JUN 3, 2019, View Source [SID1234542351]). The presentation and one-on-one discussions will launch the privately held company with a portfolio of over 20 first in class biological molecules deployed to orchestrate the innate and adaptive immune system, and will feature clinical updates of multiple trials with registrational intent.

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Conference Details:

Event: Jefferies 2019 Annual Healthcare Conference

Date/Time: Tuesday, June 4, 2019, Presentation at 8:00am ET

Location: New York, NY

For more information regarding ImmunityBio please visit www.ImmunityBio.com

On June 3, 2019 Heat Biologics, Inc. (NASDAQ: HTBX), a biopharmaceutical company developing therapies designed to activate a patient’s immune system against cancer, reported compelling new interim results from its ongoing Phase 2 study investigating HS-110 in combination with Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, nivolumab (Opdivo) (Press release, Heat Biologics, JUN 3, 2019, View Source [SID1234536792]). The updated results were obtained from Cohort B patients whose data has matured an additional 3 months since last reported at the ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium in February of this year. This data may represent the first Phase 2 data showing clinical activity in non-small cell lung cancer (NSCLC) patients whose disease has progressed after prior treatment with a checkpoint inhibitor (CPI). The Cohort B results were presented yesterday at the2019American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting poster session.

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COL(ret) George E Peoples, MD, FACS, Heat’s Chief Medical Advisor, noted, "These latest Cohort B data provides us even greater confidence that the addition of HS-110 to nivolumab may restore anti-tumor activity in patients whose disease has progressed after treatment with a CPI. Of particular note, 4 out of 5 evaluable patients in Cohort B with PD-L1 negative tumors achieved disease stabilization and 4 out of 7 evaluable patients with low CD8+ TIL levels in their tumors achieved disease stabilization. We are encouraged by these positive results and look forward to reporting additional data later this year."

Jeff Hutchins, Ph.D., Heat’s Chief Scientific and Operating Officer said, "The fact that we saw tumor shrinkage in 35% of patients and disease control in 55% of patients whose disease has progressed after treatment with a CPI supports our mechanistic hypothesis that the broad, T-cell mediated immune response activated by HS-110 may improve clinical outcomes for patients who have lost the benefit of treatment with a checkpoint inhibitor. It is also important to note that the occurrence of dermal injection site reactions is associated with statistically significant improved progression free survival and overall survival, providing further support for the mechanism of action of HS-110."

Highlights for Cohort B patients arepresented below:

HS-110 in combination with nivolumab demonstrates clinical activity i’difficult to treat’ low CD8+ TIL (≤10%) and PD-L1 negative (<1%) tumors:
4 out of 5 evaluable patients with PD-L1 negative tumors achieved disease stabilization, 1 of which was a RECIST partial response.
4 out of 7 evaluable patients with low CD8+ TIL tumors achieved disease stabilization, 2 of which were RECIST partial responses.
The addition of HS-110 to nivolumab may restore clinical benefit to patients whose disease has progressed after CPI treatment failure:
Tumor shrinkage observed in 35% of patients
Disease control rate of 55%
Median Progression-Free Survival (mPFS) of 2.7 months
Median Overall Survival (mOS) not yet reached
The occurrence of any grade dermal Injection Site Reaction during treatment (Y/N) is associated with improved Progression-Free Survival and Overall Survival:
mPFS: NR vs 1.8 months; HR 0.17 (95% CI, 0.03-0.84); p=0.013
mOS: NR vs 5 months; HR 0.13 (95% CI, 0.02-0.71); p=0.002
Treatment with HS-110 in combination with nivolumab was well tolerated, with no additional toxicities beyond those observed with single agent CPI therapy.

Trial results are summarized in the official 2019 ASCO (Free ASCO Whitepaper)Annual Meeting poster.

Trial Design

The Phase 2 trial is designed to evaluate the safety and efficacy of HS-110 combined with an immune checkpoint inhibitor for the treatment of advanced non-small cell lung cancer. Cohort B consists of patients who received a minimum of 4 months of treatment with a checkpoint inhibitor (CPI) as part of their prior therapy, but subsequently had documented progressive disease. Patients receive weekly HS-110 (1 x 107 cells) administered as 5 intradermal 0.1 mL injections for 18 weeks in combination with bi-weekly nivolumab 240 mg IV administered until confirmed disease progression or unacceptable toxicity, whichever occurs first. The primary endpoint is objective response rate (ORR); secondary endpoints include overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and duration of response (DOR). Exploratory endpoints include correlation of clinical outcomes to baseline CD8+ TILs, PD-L1 expression, peripheral blood tumor mutation burden and ELISPOT analysis.

On June 3, 2019 Novartis reported new data and clinical trial updates in NSCLC at the ASCO (Free ASCO Whitepaper) 2019 Annual Meeting. This includes primary efficacy results from the GEOMETRY mono-1 Phase II clinical trial demonstrating that investigational MET inhibitor capmatinib (INC280) shows promise as a potential treatment option for patients with locally advanced or metastatic NSCLC that harbor MET exon-14 skipping mutation (Press release, Novartis, JUN 3, 2019, View Source [SID1234536809]). There are currently no approved targeted therapies to treat this particularly aggressive form of NSCLC. Results of the Phase II study will be presented at an oral session today at ASCO (Free ASCO Whitepaper), June 3, 2019, at 8:00 a.m. CDT (Abstract #9004)[1].

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GEOMETRY mono-1 is an international, prospective, multi-cohort, non-randomized, open-label study evaluating 97 adult patients with locally advanced or metastatic NSCLC harboring MET exon-14 skipping mutation who received capmatinib tablets 400 mg orally twice daily. Primary efficacy results among treatment-naive patients (Cohort 5b: 28 patients) were a 68% overall response rate (ORR) based on the Blinded Independent Review Committee (BIRC) assessment per RECIST v1.1 (95% CI: (47.6 – 84.1)). Forty-one percent of previously treated NSCLC patients (Cohort 4: 69 patients) also responded (95% CI: (28.9 – 53.1)). Data on median duration of response (DOR), a key secondary endpoint, was 11.14 months (95% CI: (5.55 – NE)) and 9.72 months (95% CI: (5.55 – 12.98)), respectively. Intracranial activity in 54% (n=7/13) of patients, including some cases of complete resolution of brain lesions, was also observed by ad hoc neuro-radiologist review in patients with brain lesions. All results were based on independent assessment by the BIRC, and all tumor CT scans were evaluated in parallel by two radiologists to confirm the response.

The most common treatment related adverse events (AE) (>=10% all grades) across all cohorts (n=334), were peripheral edema (42%), nausea (33%), creatinine increase (20%), vomiting (19%), fatigue (14%), decreased appetite (13%) and diarrhea (11%); the majority of the AEs were grades 1/2.

"New lung cancer treatment options are critical, as this deadly disease affects more than 2 million new patients around the world each year," said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis. "The GEOMETRY mono-1 results are encouraging, and we look forward to discussing these results with health authorities with the hope of bringing this targeted treatment option to people with this aggressive type of lung cancer."

Capmatinib Granted Orphan Drug and Breakthrough Therapy Designation Status
The U.S. Food and Drug Administration recently granted capmatinib Breakthrough Therapy Designation for patients with metastatic NSCLC harboring MET exon-14 skipping mutation with disease progression on or after platinum-based chemotherapy. Previously, both the U.S. FDA and Japan’s Pharmaceuticals and Medical Devices Agency recognized capmatinib with Orphan Drug status. It is estimated that 3% to 4% of all patients with NSCLC have an identified MET mutation[3].

"The efficacy observed with capmatinib in the GEOMETRY mono-1 trial is promising," said Juergen Wolf, MD, University Hospital, Cologne. "In addition to positive overall response rate among first-line patients with the MET mutation, the duration for the responses, including the activity in the brain, and capmatinib’s safety profile are important milestones for this patient population. As a group, patients with MET mutated NSCLC often require special clinical considerations, as they are generally older and with poor prognosis further limiting their treatment options."

About GEOMETRY mono-1
GEOMETRY mono-1 is an international, prospective, multi-cohort, non-randomized, open-label Phase II study to evaluate the efficacy and safety of single-agent capmatinib (INC280) in adult patients with EGFR wildtype, ALK-negative rearrangement, advanced NSCLC harboring MET amplification and/or mutations. Patients with locally advanced or metastatic NSCLC harboring MET exon-14 skipping mutation (centrally confirmed) were assigned to Cohorts 4 (previously treated patients) or 5B (treatment-naive), regardless of MET amplification/gene copy number, and received 400 mg capmatinib tablets orally twice daily. The primary endpoint was ORR based on the BIRC assessment per RECIST v1.1. The key secondary endpoint was duration of response (DOR) by the BIRC. The GEOMETRY mono-1 study found an ORR in the treatment-naive patients (n=28) of 67.9% (95% CI: 47.6 – 84.1) and an ORR of 40.6% (95% CI: 28.9 – 53.1) in the previously treated patients (n=69). Median DOR was 11.14 months (95% CI: 5.55-NE) in treatment-naive patients and 9.72 months (95% CI: 5.55-12.98) in previously treated patients[1].

The most common treatment-related AEs included peripheral edema, nausea, creatinine increase and vomiting. Of patients treated with capmatinib, 84% experienced an AE, with 36% having grade 3/4 AEs (only 4.5% were Grade 4)[1].

Capmatinib (INC280) is an investigational, oral and selective MET inhibitor licensed to Novartis by Incyte Corporation in 2009. Under the Agreement, Incyte granted Novartis worldwide exclusive development and commercialization rights to capmatinib and certain back-up compounds in all indications.

Studying Tumor-Promoting Inflammation in Lung Cancer – Ongoing CANOPY Trials
Trials in Progress (TiP) updates on the CANOPY clinical program were also included in the ASCO (Free ASCO Whitepaper) updates. CANOPY is made up of three randomized, double-blind and placebo-controlled Phase III trials evaluating canakinumab (ACZ885), a selective IL-1ß inhibitor (Abstract #TPS9124) [4],[5].

CANOPY-A is a Phase III multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of canakinumab as adjuvant therapy in adult subjects with stages II-IIIA and NSCLC following complete surgical resection. The primary endpoint is disease-free survival (Abstract #7013).
CANOPY-1 is a randomized, double-blind, placebo-controlled, Phase III study investigating canakinumab versus placebo in combination with platinum-based chemotherapy (CTx) and pembrolizumab in previously untreated patients with stage IIIB/IIC-IV squamous and non-squamous NSCLC. The study will evaluate the incidence of dose-limiting toxicity (DLT) in the first 42 days of treatment, as well as PFS and overall survival (OS).
CANOPY-2 is a randomized, double-blind, placebo-controlled, Phase III study investigating canakinumab or placebo plus docetaxel in stage IIIB-IV NSCLC patients previously treated with PD-1 or PD-L1 inhibitors, as well as CTx. The primary endpoints are incidence of DLT in the first 42 days of treatment and OS.
Novartis Commitment to Lung Cancer
Worldwide, lung cancer causes more deaths than colon, breast and prostate cancer combined, and more than 2 million new cases of lung cancer are diagnosed each year[2]. Despite treatment advances, patients with NSCLC still have a poor prognosis and limited treatment options. This includes the nearly 70% of NSCLC patients who have a genomic mutation that may be targeted with available therapies[6]. To determine the most appropriate treatment, medical organizations recommend genomic testing for patients with lung cancer[7].

Novartis Oncology’s research has helped transform treatment approaches for patients living with NSCLC. Novartis continues its commitment to the global lung cancer community through ongoing studies, as well as the exploration of investigational compounds in NSCLC, including those that target genetic biomarkers and tumor promoting inflammation.

On June 3, 2019 Provectus (OTCQB: PVCT) reported that preliminary safety, response, biomarker, and quality of life results from the Company’s ongoing Phase 1 clinical trial of single agent PV-10 for the treatment of symptomatic neuroendocrine tumors (NET) metastatic to the liver (mNET) were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2019 Annual Meeting, held in Chicago, IL from May 31-June 4, 2019 (Press release, Provectus Biopharmaceuticals, JUN 3, 2019, View Source [SID1234536830]). Intralesional injection of oncolytic immunotherapy PV-10 can yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells.1-5 PV-10 clinical development includes cutaneous melanoma, hepatocellular carcinoma, and metastatic liver cancers such as uveal melanoma in single-agent and combination therapy settings.

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This single-center Phase 1 study is being conducted at The Queen Elizabeth Hospital in Adelaide, Australia to evaluate the potential safety, tolerability, and preliminary efficacy of PV-10 in mNET patients (NCT02693067). The primary endpoint for the trial is safety, and secondary endpoints include objective response rate (ORR) of injected target and measurable bystander lesions, target lesion somatostatin receptor expression, and biochemical response. Six patients in the first cohort each received one percutaneously-administered injection of PV-10 to one target lesion per treatment cycle. Patients in the second cohort can receive PV-10 injection of multiple lesions per cycle (2 of 6 patients in the second cohort have received at least one cycle of PV-10 thus far).

Preliminary Results from the Presentation at ASCO (Free ASCO Whitepaper):

Baseline characteristics (N=6): 67% men; median age of 65 years (range 47-72).

Disease characteristics: primary tumor site – 50% small intestine, 33% pancreas, and 17% caecal; 87% Grade 2 (well differentiated, intermediate); all patients were refractory to systemic somatostatin analogues and peptide receptor radionuclide therapy.

PV-10 treatment summary: Median of 1 cycle (mean 1.7, range 1-4) and median dose per cycle of 2.1 mL (range 1.0-5.8 mL).

Preliminary safety: Acceptable toxicity (e.g., post-procedure pain, carcinoid flare, nausea); liver function tests have remained stable.

Preliminary target lesion efficacy: 50% objective response and 87% disease control; response follow-up in 3 patients (50%) is ongoing

Preliminary patient-level efficacy data were not available at the time of data cutoff.

Preliminary clinical and biomarker outcomes: overall quality of life scores were stable in 5 patients (87%); Chromogranin A responses were stable in 5 patients (87%)

Preliminary changes in peripheral blood mononuclear cells were not available at the time of data cutoff.
Dominic Rodrigues, Vice Chair of the Company’s Board of Directors, said, "Patients with neuroendocrine tumors remain a cancer population with high unmet medical need. This poster describes Provectus’ continued progress towards demonstrating the widespread use of small molecule oncolytic immunotherapy PV-10 for the treatment of immunologically ‘cold’ or non-T cell inflamed tumor types."

Mr. Rodrigues added, "Patients in this study experienced no safety concerns from single or repeated injections of PV-10 into the liver. Furthermore, we believe PV-10 treatment provided in this trial yielded encouraging, preliminary evidence of single-agent drug activity, including both local and systemic disease control."

A copy of the ASCO (Free ASCO Whitepaper) poster presentation is currently available on Provectus’ website at View Source

About Neuroendocrine Tumors

NET associated with the gastrointestinal tract are frequently indolent but troublesome as a result of endocrine secretory properties and a propensity for metastasis to the liver, nodes, and lungs. mNET located in the midgut and liver often secrete vasoactive products, giving rise to "Carcinoid Syndrome" (e.g., flushing, diarrhea, wheezing, abdominal cramps, and peripheral edema).

About PV-10

PV-10 causes acute oncolytic destruction of injected tumors, releasing damage associated molecular pattern molecules (DAMPs) and tumor antigens that initiate an immunologic cascade where local response by the innate immune system facilitates systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. T cell function can be further augmented by combining PV-10 with immune checkpoint inhibition.

PV-10 is undergoing clinical study for adult solid tumor cancers like melanoma and cancers of the liver (including metastatic symptomatic neuroendocrine tumors and metastatic uveal melanoma) and preclinical study for pediatric cancers like neuroblastoma5, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma.

Orphan drug designation status has been granted to PV-10 by the U.S. Food and Drug Administration for the treatments of metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.

PV-10’s active pharmaceutical ingredient is rose bengal disodium (RB) (4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein disodium salt), a small molecule halogenated xanthene. PV-10 drug product is a bright rose red solution containing 10% w/v RB in 0.9% saline for injection, which is supplied in single-use glass vials containing 5 mL (to deliver) of solution and administered without dilution to solid tumors via intratumoral injection.

Provectus’ intellectual property includes a family of US and international patents that protect the process by which pharmaceutical grade RB and related xanthenes are produced, reducing the formation of previously unknown transhalogenated impurities that exist in commercial grade RB in uncontrolled amounts. The requirement to identify and control these substances is in accordance with International Conference on Harmonisation (ICH) guidelines for the manufacturing of active pharmaceutical ingredient that is suitable for clinical trial and commercial pharmaceutical use. US patent numbers are 8,530,675, 9,273,022, and 9,422,260; patent expirations range from 2030 to 2031.