On July 9, 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 the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for CLR 131 in relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL) (Press release, Cellectar Biosciences, JUL 9, 2019, View Source [SID1234537452]). CLR 131 is the company’s small-molecule, cancer-targeting radiotherapeutic Phospholipid Drug Conjugate (PDC) designed to deliver cytotoxic radiation directly and selectively to cancer cells and cancer stem cells. It is currently being evaluated in Cellectar’s ongoing Phase 2 CLOVER-1 clinical study in patients with relapsed or refractory select B-Cell lymphomas.

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 to receive FDA’s Fast Track Designation for CLR 131. This designation supports our efforts to more rapidly provide a new therapeutic option for patients with relapsed or refractory DLBCL, a disease that typically has a very poor prognosis and low rates of survival," said James Caruso, president and CEO of Cellectar. "As announced last year, data from the DLBCL cohort in our ongoing CLOVER-1 trial showed an encouraging 33% overall response rate at the time of the interim assessment. Patients prior to the interim assessment received a single 25.0 mCi/m2 dose of CLR 131. Dosing in the Phase 2 CLOVER-1 study has increased, and patients are now receiving 37.50 mCi/m2 fractionated in two administrations of CLR 131. We are optimistic that CLR 131 has the potential to provide a meaningful treatment option for these patients and look forward to additional data in 2019."

Fast Track Designation

Fast Track Designation is granted to drugs being developed for the treatment of serious or life-threatening diseases or conditions where there is an unmet medical need. The purpose of the Fast Track Designation provision is to help facilitate development and expedite the review and potential approval of drugs to treat serious and life-threatening conditions.

Sponsors of drugs that receive Fast Track Designation have the opportunity for more frequent interactions with the FDA review team throughout the development program. These can include meetings to discuss study design, data required to support approval, or other aspects of the clinical program. Additionally, products that have been granted Fast Track Designation may be eligible for priority review of a New Drug Application (NDA) and the FDA may consider reviewing portions of an NDA before the sponsor submits the complete application (Rolling Review).

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 37.5mCi/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, targeted Phospholipid Drug Conjugate (PDC) designed to deliver cytotoxic radiation directly to cancer cells, while limiting exposure to healthy cells. CLR 131 is the company’s lead product candidate and is currently being evaluated in a Phase 2 study in B-Cell lymphomas, and two Phase 1 dose-escalating clinical studies, one in multiple myeloma and one in pediatric solid tumors and lymphoma. CLR 131 was granted Orphan Drug designation for the treatment of multiple myeloma, and was granted Orphan Drug and Rare Pediatric Disease for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma.

On July 9, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, Precision Cancer Medicine oncology therapeutics company, reported the initiation of patient enrollment of its Phase 1b/2 study of onvansertib in combination with FOLFIRI and Avastin (bevacizumab) for second-line treatment of patients with metastatic colorectal cancer (mCRC) with a KRAS mutation (NCT03829410) (Press release, Trovagene, JUL 9, 2019, View Source [SID1234537449]). Trovagene is developing onvansertib, a first-in-class, third-generation, oral and highly-selective Polo-like Kinase 1 (PLK1) inhibitor that targets the key master regulator of tumor cell division, for the treatment of leukemias, lymphomas and solid tumor cancers. The trial is being conducted at USC Norris Comprehensive Cancer Center, Hoag Cancer Center and The Mayo Clinic, under the leadership of recognized colorectal cancer key opinion leaders, Heinz-Josef Lenz, MD, FACP, Section Head of GI Oncology and Co-Director of the Colorectal Center at USC Norris, and Afsaneh Barzi, MD, PhD, oncologist at USC Norris and principal investigator of the trial.

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!

"It is well-recognized that there is a significant medical need for better treatment options for KRAS-mutated gastrointestinal cancers," said Dr. Lenz, who is also a professor of medicine at Keck School of Medicine of USC. "We are targeting these patients in this trial because in onvansertib preclinical studies, tumor cells that harbor KRAS mutations, when treated with onvansertib, have what we call ‘synthetic lethality,’ or in other words, have a greater susceptibility to tumor cell death."

"We look forward to this trial and the opportunity to examine a potential therapy for a patient population in need of options," said Dr. Barzi, who is also an associate professor of clinical medicine at the Keck School. "Use of genomic profiling to understand the molecular underpinnings of mCRC is critical to our precision medicine approach and treating our patients. In addition, KRAS profiling in this trial, by a simple blood test, is anticipated to enable us to get a very early indication of response to treatment. This is key not only for this trial, but for how we can quickly assess response and, in real-time, integrate this approach as part of future patient management."

"Our Phase 1b/2 trial is an opportunity for us to demonstrate the potential for onvansertib to provide a new, safe and efficacious treatment for patients who are faced with a poor prognosis and who have limited therapeutic options," said Thomas Adams, PhD, Chief Executive Officer and Chairman of Trovagene. "Importantly, we have preclinical in-vitro and in-vivo data demonstrating that tumors harboring KRAS mutations are more sensitive to onvansertib-induced tumor death. Furthermore, onvansertib has significant synergy in combination with Camptosar (irinotecan) and an additive effect with Avastin, both of which are components of the standard-of-care treatment regimen that will be used in our trial. We are excited to commence this trial, which already has funding in place through a previously announced agreement with PoC Capital, LLC."

About Colorectal Cancer

Colorectal cancer (CRC) is the second leading cause of cancer mortality in the U.S. Despite significant progress in the treatment of mCRC, the majority of patients with metastatic disease succumb to the disease. Therefore, improving the treatment options and effectiveness is critical in changing the outcomes for this patient population. KRAS is a common mutation in the CRC population and approximately 50% of patients with CRC carry RAS mutations. In the U.S., FOLFOX (5-flourouracil, leucovorin, oxaliplatin) and FOLFIRI (fluorouracil, leucovorin, irinotecan) are standard-of-care options for patients with metastatic CRC in the first-line setting, irrespective of the KRAS mutation status. The majority of CRC patients respond to first-line therapy with a response rate of > 50%. The efficacy of second-line therapy in terms of survival prolongation and response remains very limited, particularly in the KRAS-mutated population, where treatment options are more restricted. FOLFIRI (a chemotherapy regimen of irinotecan, fluorouracil [5-FU], and leucovorin) + Avastin (bevacizumab) in the second-line setting is the standard treatment in US. The response rate in the second-line setting is less than 5% as reported in a large international trial of bevacizumab in the second-line setting.

About the Phase 1b/2 Clinical Trial of Onvansertib in mCRC

In this open-label, Phase 1b/2 trial, onvansertib in combination with standard-of-care FOLFIRI and Avastin is being evaluated for safety and efficacy. The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second‑Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation (NCT03829410), will enroll up to 44 patients with a KRAS mutation and histologically confirmed metastatic and unresectable disease. In addition, patients must have failed treatment or be intolerant of FOLFOX (fluoropyrimidine and oxaliplatin) with or without Avastin (bevacizumab). The trial is being conducted at three prestigious cancer centers: USC Norris Comprehensive Cancer Center, Hoag Cancer Center and The Mayo Clinic.

About Onvansertib

Onvansertib is a first-in-class, third-generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1) enzyme, which is over-expressed in multiple cancers, including leukemias, lymphomas and solid tumors. Onvansertib targets the PLK1 isoform only (not PLK2 or PLK3), is orally administered and has a 24-hour half-life with only mild-to-moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.

Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including irinotecan, FLT3 and HDAC inhibitors, taxanes and cytotoxins. Trovagene believes the combination of onvansertib with other compounds has the potential to improve clinical efficacy in acute myeloid leukemia (AML), metastatic castration-resistant prostate cancer (mCRPC), non-Hodgkin lymphoma (NHL), colorectal cancer, triple-negative breast cancer (TNBC), as well as other types of cancer.

Trovagene has an ongoing Phase 1b/2 clinical trial of onvansertib in combination with low-dose cytarabine or decitabine in patients with relapsed or refractory AML that was accepted by the National Library of Medicine (NLM) and is now publicly viewable on www.clinicaltrials.gov. The NCT number assigned by clinicaltrials.gov for this study is NCT03303339. Onvansertib has been granted orphan drug designation by the FDA in the U.S. and by the EC in the European Union for the treatment of patients with AML.

Trovagene has an ongoing Phase 2 clinical trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with mCRPC who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving Zytiga. The trial was accepted by the NLM and is now publicly viewable on www.clinicaltrials.gov. The NCT number assigned by clinicaltrials.gov for this study is NCT03414034.

Trovagene licensed onvansertib (also known as NMS-1286937 and PCM-075) from Nerviano Medical Sciences (NMS), the largest oncology-focused research and development company in Italy, and a leader in protein kinase drug development. NMS has an excellent track record of licensing innovative drugs to pharma/biotech companies, including Array (recently acquired by Pfizer), Ignyta (acquired by Roche) and Genentech.

On July 9, 2019 Eli Lilly and Company (NYSE: LLY) reported that it will announce its second-quarter 2019 financial results on Tuesday, July 30, 2019 (Press release, Eli Lilly, JUL 9, 2019, View Source [SID1234537448]). Lilly will also conduct a conference call on that day with the investment community and media to further detail the company’s financial performance.

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 conference call will begin at 9 a.m. Eastern time. Investors, media and the general public can access a live webcast of the conference call through a link that will be posted on Lilly’s website at View Source A replay will also be available on the website following the conference call.

On July 9, 2019 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported a clinical collaboration agreement with Novartis to evaluate the combination of MRTX849, Mirati’s investigational KRAS G12C inhibitor and TNO155, Novartis’ investigational SHP2 inhibitor, in patients with advanced solid tumors that harbor KRAS G12C mutations (Press release, Mirati, JUL 9, 2019, View Source [SID1234537447]).

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!

SHP2 is an important mediator of cellular signaling through the RAS/MAP kinase pathway and is frequently overactive in various types of cancer. Preclinical data has shown that the combination of a KRAS G12C inhibitor with a SHP2 inhibitor results in increased anti-tumor activity based on their complementary mechanisms of action.

"In our non-clinical studies, the combination of MRTX849 with a SHP2 inhibitor demonstrated a clear impact on KRAS signaling and resulted in a significant increase in anti-tumor activity in some tumors versus either investigational drug alone," said James Christensen, Ph.D., Executive Vice President and Chief Scientific Officer, Mirati Therapeutics. "We believe this collaboration will strengthen and broaden our KRAS program, potentially increasing the efficacy of MRTX849 and bringing another option to patients with KRAS G12C mutations who have traditionally exhibited resistance with other therapies."

Under terms of the non-exclusive collaboration, Mirati will sponsor the trial and Novartis and Mirati will jointly oversee and share the costs of clinical development activities for the combined therapy. Novartis will provide TNO155 at no cost.

About MRTX849

MRTX849 is an investigational, orally-available small molecule that is designed to potently and selectively inhibit a form of KRAS which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of NSCLC adenocarcinoma patients, 4% of colorectal cancer patients, and subsets of other types of cancer. Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. MRTX849 is being evaluated in a Phase 1/2 trial treating patients with molecularly-identified, KRAS G12C-positive advanced solid tumors.

On July 9, 2019 CStone Pharmaceuticals ("CStone", HKEX: 2616) reported that the first patient has been dosed in China with avapritinib in the ongoing global Phase III VOYAGER clinical trial (Press release, CStone Pharmaceauticals, JUL 9, 2019, View Source [SID1234537446]). This study is designed to evaluate the safety and efficacy of avapritinib as a third-line or fourth-line treatment for patients with gastrointestinal stromal tumors (GIST), in comparison with that of regorafenib, the current standard of care treatment for GIST. To be eligible, patients must have been previously treated with imatinib and one or two additional tyrosine kinase inhibitors. The trial’s primary efficacy endpoint is progression-free survival (PFS).

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!

Avapritinib, an orally available, potent and highly selective inhibitor of KIT and PDGFRA, was discovered by CStone’s partner Blueprint Medicines. Approximately 90% of GIST cases are associated with mutations of KIT and PDGFRA tyrosine kinases, leading to dysregulation of cell growth. Previously published preclinical results have shown that avapritinib can potently treat GIST associated with KIT and PDGFRA mutations.

Clinical data from the ongoing Phase I NAVIGATOR study presented in June 2019 demonstrated encouraging anti-tumor activity and favorable tolerability in patients with PDGFRA Exon 18 mutant and fourth-line GIST, two populations with no effective therapies. Blueprint Medicines has recently submitted a New Drug Application (NDA) to the U.S. FDA for these indications.

As of the data cutoff date of November 16, 2018:

In 43 evaluable patients with PDGFRA Exon 18 mutant GIST (including 38 patients with PDGFRα D842V-driven GIST), the ORR was 86 percent and the median duration of response was not reached.
In 111 evaluable patients with fourth-line GIST, the ORR was 22 percent and the median duration of response was 10.2 months.
Avapritinib had a favorable safety profile, with most adverse events determined by investigators to be Grade 1 or 2 as of the data cutoff date.
Dr. Frank Jiang, Chairman and CEO of CStone, commented: "Development of precision therapy in oncology is one of CStone’s core strategies. GIST is a rare disease, and avapritinib has demonstrated its efficacy in treating GIST patients with tumor mutations resistant to currently available therapies. Our partner Blueprint Medicines has submitted the NDA for avapritinib to the U.S. FDA, and the agent is expected to be CStone’s second product that gets approved in the U.S. As we continue to make progress with the VOYAGER trial in China, we hope that the clinical data can soon support the approval of avapritinib in the country, and ultimately allow the product to benefit patients with advanced GIST who now lack effective treatments."

CStone’s Chief Medical Officer Dr. Jason Yang noted: "We are pleased that the first Chinese patient has been enrolled and dosed in this Phase III trial of avapritinib as a third-line agent for advanced GIST. We will do our best to have more Chinese centers participate in this important global clinical study."

About GIST

GIST is a sarcoma, or tumor of bone or connective tissue, of the gastrointestinal (GI) tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50 to 80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging and, in rare cases, tumor rupture or GI obstruction.

Most GIST cases are caused by a spectrum of clinically relevant mutations that force the KIT or PDGFRA protein kinases into an increasingly active state. Because currently available therapies primarily bind to the inactive protein conformations, certain primary and secondary mutations typically lead to treatment resistance and disease progression.

In unresectable or metastatic GIST, clinical benefits from existing treatments can vary by mutation type. Mutational testing is critical to tailor therapy to the underlying disease driver and is recommended in expert guidelines. Currently, there are no approved therapies for patients with KIT-driven GIST whose disease progresses beyond imatinib, sunitinib and regorafenib. In patients with metastatic PDGFRα D842V-driven GIST, progression occurs in a median of approximately three to four months with available therapy.

About Avapritinib

Avapritinib is an investigational, oral precision therapy that selectively and potently inhibits KIT and PDGFRA mutant kinases. It is a type 1 inhibitor designed to target the active kinase conformation; all oncogenic kinases signal via this conformation. Avapritinib has demonstrated broad inhibition of KIT and PDGFRA mutations associated with GIST, including potent activity against activation loop mutations that are associated with resistance to currently approved therapies.

Blueprint Medicines is initially developing avapritinib for the treatment of advanced GIST, advanced systemic mastocytosis (SM), and indolent and smoldering SM. The FDA has granted Breakthrough Therapy Designation to avapritinib for two indications: one for the treatment of unresectable or metastatic GIST harboring the PDGFRα D842V mutation and one for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for avapritinib in the rest of the world.