FDA Grants Rare Pediatric Disease Designation to Cellectar Biosciences’ CLR 131 for the Treatment of Osteosarcoma

On September 17, 2018 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 that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation (RPDD) to CLR 131 for the treatment of osteosarcoma, a rare pediatric cancer (Press release, Cellectar Biosciences, SEP 17, 2018, View Source [SID1234530175]). CLR 131 is Cellectar’s lead Phospholipid Drug Conjugate (PDC) product candidate.

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"CLR 131 has demonstrated promise as an anticancer agent in preclinical and clinical settings, and we are working now to establish its impact on various rare and deadly pediatric cancers," said John Friend, M.D., chief medical officer of Cellectar. "Cellectar is pleased to have the opportunity to work closely with the FDA on our planned Phase 1 trial for these indications and we remain committed to advancing the pediatric programs as rapidly as possible."

Since May 2018 the company has received RPDD for CLR 131 in four pediatric cancers: neuroblastoma, rhabdomyosarcoma, Ewing’s Sarcoma and, most recently, osteosarcoma. Should any of these indications reach approval, the RPDD may enable Cellectar to receive a priority review voucher. Priority review vouchers can be used by the sponsor to receive Priority Review for a future NDA or BLA submission, which would reduce the FDA review time from 12 months to six months. Currently, these vouchers can also be transferred or sold to another entity. Over the last 16 months, five priority review vouchers were sold for between $110 million and $150 million each.

The FDA grants Rare Pediatric Disease Designation for diseases that primarily affect children from birth to 18 years old, and affect fewer than 200,000 persons in the U.S. This program is intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases.

About Osteosarcoma

Osteosarcoma derives from bone forming mesenchymal, or connective tissue, cells and is the most commonly diagnosed primary bone malignancy among children and adolescents. The incidence is about 4.4 cases per 1 million per year in children younger than 24 years [Mirabello 2009]. While there is a 70% cure rate among patients with localized disease, 5-year overall survival rates are approximately 20% for among patients who develop metastatic disease [Saraf 2018]. Additionally, among patients who experience disease progression or recurrence survival for is less than 30% [Chou 2005].

About CLR 131

CLR 131 is Cellectar’s investigational radioiodinated PDC therapy that exploits the tumor-targeting properties of the company’s proprietary phospholipid ether (PLE) and PLE analogs to selectively deliver radiation to malignant tumor cells, thus minimizing radiation exposure to normal tissues. CLR 131 is in a Phase 2 clinical study in R/R MM and a range of B-cell malignancies and a Phase 1b clinical study in patients with R/R MM exploring fractionated dosing. The objective of the multicenter, open-label, Phase 1b dose-escalation study is the characterization of safety and tolerability of CLR 131 in patients with R/R MM. Patients in Cohorts 1-4 received single doses of CLR 131 ranging from 12.5 mCi/m2 to 31.25 mCi/m2. All study doses have been deemed safe and well tolerated by an independent Data Monitoring Committee. The company is currently initiating a Phase 1 study with CLR 131 in pediatric solid tumors and lymphoma and is planning a second Phase 1 study in combination with external beam radiation for head and neck cancer.

G1 Therapeutics to Report Myelopreservation Data from Randomized Phase 2 Trial of Trilaciclib/Chemotherapy/Tecentriq® in Small Cell Lung Cancer in Fourth Quarter 2018

On September 17, 2018 G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, reported that it is expediting analyses of myelopreservation data from its randomized Phase 2 trial of trilaciclib in combination with chemotherapy and Tecentriq (atezolizumab) in first-line small cell lung cancer (SCLC) (Press release, G1 Therapeutics, SEP 17, 2018, View Source [SID1234529790]). Myelopreservation results from the trial will be reported in the fourth quarter of 2018.

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"We elected to make myelopreservation the primary outcome of the randomized trilaciclib/chemotherapy/Tecentriq trial based on the strength of the first-line small cell lung cancer myelopreservation results from our randomized Phase 2 trilaciclib/chemotherapy trial, which we reported in March," said Raj Malik, M.D., Chief Medical Officer and Senior Vice President, Research and Development. "This protocol amendment, which we have discussed with U.S. and European regulatory authorities, enables us to accelerate analyses of mature myelopreservation data collected from the trilaciclib/chemotherapy/Tecentriq trial. The trial will remain blinded to investigators and participants, with no impact on our timeline to report overall survival data."

This randomized, double-blind Phase 2 trial enrolled 107 patients to receive trilaciclib or placebo in combination with chemotherapy (carboplatin + etoposide) and Tecentriq as first-line treatment for SCLC. The trial is evaluating the myelopreservation potential of trilaciclib. Myelopreservation is the ability to preserve hematopoietic stem and progenitor cell function, as well as immune system function, during chemotherapy. Anti-tumor efficacy measures including overall response rate, progression-free survival and overall survival are also being evaluated. Under the revised protocol, myelopreservation results are now the primary outcome and overall survival is being assessed as a secondary outcome. The trial completed enrollment in February 2018.

"Data from the trilaciclib/chemotherapy/Tecentriq trial have the potential to confirm the myelopreservation results observed in our randomized Phase 2 trial of trilaciclib in combination with chemotherapy. Both trials evaluated trilaciclib in first-line small cell lung cancer using the same chemotherapy backbone," said Mark Velleca, M.D., Ph.D., Chief Executive Officer. "By the end of the year we will have myelopreservation data from all four randomized Phase 2 trials of trilaciclib, including three in small cell lung cancer and one in triple negative breast cancer. In these trials, trilaciclib was used in first-, second- and third-line settings in combination with a variety of chemotherapy regimens. We plan to discuss the totality of the data, which includes approximately three hundred participants who received trilaciclib, with U.S. and European regulatory authorities in the first half of 2019."

Webcast and Conference Call

The G1 management team will host a webcast and conference call at 8:30 a.m. ET today to discuss the trilaciclib clinical development program. The live call may be accessed by dialing 866-763-6020

About Trilaciclib

Trilaciclib is a first-in-class myelopreservation therapy designed to preserve hematopoietic stem and progenitor cell function, as well as immune system function, during chemotherapy. Trilaciclib is a short-acting intravenous CDK4/6 inhibitor administered prior to chemotherapy and has the potential to significantly improve treatment outcomes.

Trilaciclib is being evaluated in four randomized Phase 2 clinical trials. In March 2018, G1 announced positive Phase 2 data showing myelopreservation benefits in newly diagnosed, treatment-naive small cell lung cancer (SCLC) patients (NCT02499770). Additional results from this trial will be reported at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress being held October 19-23. The company plans to report data from three other randomized Phase 2 trials in 2018: a trial in combination with chemotherapy and Tecentriq in first-line SCLC, (NCT03041311), a trial in combination with chemotherapy in previously treated SCLC (NCT02514447), and a trial in combination with chemotherapy in triple-negative breast cancer (NCT02978716).

GamaMabs Pharma starts a phase 2 study of monoclonal antibody GM102 in patients with advanced or metastatic colorectal cancer

On September 17, 2018 GamaMabs Pharma, a biotechnology company developing optimized therapeutic antibodies targeting the Anti-Müllerian Hormone Receptor II (AMHRII) for the treatment of cancer, reported that it has dosed the first patient in its Phase 2 clinical trial – of GM102 single agent and in combination with Trifluridine/Tipiracil (Lonsurf) – in patients with advanced or metastatic colorectal cancer (CRC) (Press release, GamaMabs Pharma, SEP 17, 2018, View Source [SID1234529581]).

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GM102 is a first-in-class glyco-engineered (low-fucose) monoclonal antibody targeting tumor antigen AMHRII. AMHRII is re-expressed in approximately 70% of colorectal cancer patients. GM102 exerts its anti-tumor activity through macrophage and NK cell engagement in the tumor microenvironment, resulting in enhanced tumor phagocytosis and ADCC (Antibody Dependent Cell Cytotoxicity).

This phase 2 study resulted from collaborative research with various European academic research centers and hospitals, which unveiled a wide AMHRII expression in human CRC tumors and a substantial expression of the target on tumor cells at the membrane level. These results were published at the AACR (Free AACR Whitepaper) Annual meeting in April 2018.

"The C201 study will investigate the anti-tumor activity of GM102 in this new indication and its potential synergism with Lonsurf for patients who have progressed on prior therapies. Most CRC tumors express moderate to large macrophage infiltration. GM102 therefore has a potential to enhance macrophage phagocytosis on tumor cells in addition to acting synergistically with Lonsurf," said Isabelle Tabah-Fisch, M.D., GamaMabs’ chief medical officer. "This is a key step in the development of our molecule, which has already shown excellent tolerability in patients with gynecological cancers and first signs of activity in the first patients in the phase 1a/1b C101 study, recently presented at the ASCO (Free ASCO Whitepaper) 2018 conference."

"We are still in serious need of active drugs for our CRC patients," said Professor B. Melichar, investigator at Olomouc University Hospital, Olomouc, Czech Republic. "AMHRII is yet another unexplored target in CRC. GM102 is the latest generation immunological agent to be tested in colorectal cancers, especially those which do not respond to checkpoint inhibitors. We look forward to evaluating this new agent and I am happy to have the first patient already enrolled in the study."

The European multicenter two-parallel non-randomized cohort C201 Phase 2 study will assess objective response rates, immunological changes in the tumor microenvironment, progression-free and overall survival rates for patients with advanced/metastatic colorectal cancers treated with GM102 single agent and in combination with Lonsurf. The study will enroll patients who have progressed after at least two lines of prior systemic therapies for metastatic or locally advanced disease and have received all prior available therapies (cohort 1) or are candidates to receive Lonsurf (cohort 2).

Lonsurf (trifluridine-tipiracil hydrochloride) is a chemotherapy drug, used to treat metastatic colorectal cancer. Servier commercializes Lonsurf in Europe and other countries outside of the United States, Canada, Mexico and Asia. Taiho Pharmaceutical has the right to develop and commercialize Lonsurf in the United States, Canada, Mexico, and Asia.

AbbVie to Host Third-Quarter 2018 Earnings Conference Call

On September 17, 2018 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported that it will announce its third-quarter 2018 financial results on Friday, November 2 2018, before the market opens (Press release, AbbVie, SEP 17, 2018, View Source [SID1234529546]). AbbVie will host a live webcast of the earnings conference call at 8 a.m. Central time (9 a.m. Eastern). It will be accessible through AbbVie’s Investor Relations website investors.abbvie.com. An archived edition of the session will be available later that day.

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Mersana Announces FDA Lifts Partial Clinical Hold for XMT-1522 Phase 1 Clinical Trial to Resume Enrollment of New Patients

On september 17, 2018 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody drug conjugates (ADCs) based on its Dolaflexin and other proprietary platforms, reported that the U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold on the Phase 1 study of XMT-1522 (Press release, Mersana Therapeutics, SEP 17, 2018, View Source [SID1234529521]).

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Mersana and the FDA reached alignment on changes to the protocol, including increased monitoring as well as the exclusion of patients with advanced hepatic impairment. Although XMT-1536, Mersana’s Dolaflexin ADC targeting NaPi2b, was not subject to a clinical hold, Mersana has decided to implement similar modifications to the XMT-1536 protocol.

In addition, alternative dosing regimens will be evaluated for both clinical trials. The XMT-1522 trial will begin with a once-every-four-week dose regimen. This dosing regimen has already been implemented in the XMT-1536 trial at previously explored dose levels in order to enable a comparison of relevant doses and their impact on the safety, efficacy and PK profile of the drug candidate. The company may evaluate additional regimens as well. Data on XMT-1536 is expected in the first half of 2019.

"We are excited to resume enrollment on the XMT-1522 trial and to work with investigators to explore the full potential of both promising drug candidates in the solid tumor setting," said Anna Protopapas, Chief Executive Officer of Mersana.

About XMT-1522

XMT-1522 is a Dolaflexin ADC targeting HER2-expressing tumors. XMT-1522 contains a proprietary HER2 antibody which is conjugated with Mersana’s Dolaflexin platform — a Fleximer polymer linked with a proprietary auristatin payload. XMT-1522 provides a drug load of approximately 12 molecules per antibody, specifically designed to improve potency while simultaneously increasing tolerability. XMT-1522 has the potential to extend HER2-targeted therapy beyond the current "HER2-positive" populations into patients with lower levels of HER2 expression. The Phase 1 protocol will evaluate XMT-1522 in patients with advanced HER2-positive breast and gastric cancer, as well as advanced breast cancer with low HER2 expression and non-small cell lung cancer (NSCLC). More information on the ongoing Phase 1 clinical trial can be found at clinicaltrials.gov.

About XMT-1536

XMT-1536 is a highly potent immunoconjugate targeting the sodium-dependent phosphate transport protein (NaPi2b) and is comprised of an average of 10-15 DolaLockTM payload molecules conjugated to XMT-1535, a proprietary humanized anti-NaPi2b antibody, via the Dolaflexin ADC platform. NaPi2b is an antigen highly expressed in the majority of non-squamous NSCLC and epithelial ovarian cancer. XMT-1536 is in Phase 1 clinical trials in patients with tumors expressing NaPi2b, including ovarian cancer, NSCLC and other cancers. More information on the ongoing Phase 1 clinical trial can be found at clinicaltrials.gov.