On December 4, 2018 G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, reported preliminary anti-tumor efficacy and myelopreservation data from its randomized, open-label Phase 2 trial evaluating trilaciclib in combination with chemotherapy as a treatment for metastatic triple-negative breast cancer (mTNBC) (Press release, G1 Therapeutics, DEC 4, 2018, View Source [SID1234531965]). These data will be presented on Wednesday, December 5 at a poster discussion Spotlight Session at the 2018 San Antonio Breast Cancer Symposium (SABCS), being held in San Antonio, Texas.

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 poster is now available on the Publications page of the company’s website.

"In settings such as metastatic triple-negative breast cancer where chemotherapy is dosed until disease progression, trilaciclib has the potential to deliver both multi-lineage myelopreservation and anti-tumor efficacy benefits to patients," said Raj Malik, M.D., Chief Medical Officer and Senior Vice President, R&D. "In this trial, we observed promising early progression-free survival results favoring trilaciclib, as well as myelopreservation benefits across neutrophils, red blood cells, platelets, and lymphocytes."

Trial Design

This randomized, open-label Phase 2 clinical trial enrolled 102 patients with mTNBC who had received 0-2 prior lines of therapy in the recurrent/metastatic setting. In this three-arm trial, all patients received a chemotherapy regimen of gemcitabine and carboplatin (GC). Patients were randomized to receive GC only or GC plus one of two dosing schedules of trilaciclib: trilaciclib administered on the day of chemotherapy (GC/Tx1) or trilaciclib administered the day prior to and the day of chemotherapy (GC/Tx2).

Key Trial Findings

Preliminary median progression-free survival (PFS) was 5.4 months in the GC arm, 8.8 months in the GC/Tx1 arm (hazard ratio 0.52, p=0.0669) and 7.3 months in the GC/Tx2 arm (hazard ratio 0.49; p=0.0546). A combined analysis of trilaciclib-treated patients showed PFS of 5.4 months for the GC arm and 7.9 months for trilaciclib (hazard ratio 0.50, p=0.0189).

Preliminary objective response rate (ORR) was 29.2% in the GC arm, 43.3% in the GC/Tx1 arm and 36.7% in the GC/Tx2 arm.

PFS and ORR in the control arm were consistent with historical data1.

Overall survival (OS) data is immature. OS and updated PFS and ORR will be reported when available.

J Clin Oncol 32:3840-3847

Patients in both trilaciclib groups remained on therapy for a longer duration of time compared to GC only (median weeks: GC=14.4; GC/Tx1=20.0 weeks; GC/Tx2=19.0 weeks).

On a per-patient basis, the number of patients experiencing myelosuppression events was similar across the three arms. When adjusted for the duration of chemotherapy, the trial demonstrated that patients receiving trilaciclib experienced multi-lineage myelopreservation benefits.

Consistent with previous trilaciclib Phase 2 trials, treatment was well tolerated with no trilaciclib-related serious adverse events reported.

Poster Information

Title: Trilaciclib (T), a CDK4/6 inhibitor, dosed with gemcitabine (G), carboplatin (C) in metastatic triple negative breast cancer (mTNBC) patients: Preliminary phase 2 results

Abstract Number: 1191

Presentation Number: PD1-01

Session Title: Developmental Therapeutics

Date / Time / Location: December 5, 5-7 p.m. CST/6-8 p.m. EST, Stars at Night Ballroom 1&2, Henry B. Gonzalez Convention Center

Presenter: Joyce O’Shaughnessy, M.D. (Texas Oncology-Baylor Charles A. Sammons Cancer Center)

For more information about the 2018 San Antonio Breast Cancer Symposium, please visit View Source

About Trilaciclib

Trilaciclib is a first-in-class myelopreservation therapy designed to improve outcomes of patients who receive chemotherapy by preserving hematopoietic stem and progenitor cell (HSPC) and immune system function. Trilaciclib is a short-acting intravenous CDK4/6 inhibitor administered prior to chemotherapy.

Trilaciclib is being evaluated in four randomized Phase 2 clinical trials. G1 has reported positive results from three of these trials in 2018. Two trials showed myelopreservation benefits in newly diagnosed, treatment-naive SCLC patients. In the first trial, trilaciclib was administered in combination with a chemotherapy regimen of etoposide and carboplatin (NCT02499770); topline data were released in March and additional data were reported at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress. In the second trial, trilaciclib was administered in combination with the same chemotherapy regimen and the checkpoint inhibitor Tecentriq (atezolizumab) (NCT03041311); topline data were reported in November. Results from a trial in combination with chemotherapy in metastatic triple-negative breast cancer (NCT02978716) showing enhanced progression-free survival and multi-lineage myelopreservation benefits are being presented at the San Antonio Breast Cancer Symposium on December 5, 2018. The company plans to release topline data from a trial in combination with chemotherapy in previously treated SCLC (NCT02514447) by the end of 2018.

On December 4, 2018 The European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group and Protagen AG reported a collaboration to utilize Protagen’s Cancer Immunotherapy Array to identify autoantibody biomarkers that investigate the immunological profile and immuno-competence of long-term Glioblastoma survivors (Press release, EORTC, DEC 4, 2018, View Source [SID1234531897]).

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!

Glioblastoma is the most common glial brain tumor with an annual incidence above 3 per 100,000 population. The overall prognosis of glioblastoma patients remains poor. According to population-based data, median overall survival (OS) is still in the range of only one year and long-term survival is rare. However, a minority of glioblastoma patients survive for more than 60 months and these individuals are referred to as long-term survivors. The US-based Brain Tumor Funders Collaborative (BTFC) is supporting a large international research program that aims at better understanding which individuals with glioblastoma will ultimately become long-term survivors.

Through the present new collaboration, Protagen and the EORTC Brain Tumor Group will utilize Protagen’s Cancer Immunotherapy Array to understand the immunological profile of such patients to learn how to predict such long-term survival and potentially define novel pathways for therapeutic intervention.

Prof. Michael Weller, Head of the Brain Tumor Center at University Hospital Zurich and Chairman of the EORTC Brain Tumor Group, stated: "In our network we have followed and investigated this group of long-term glioblastoma survivors for many years. The focus has been to understand the molecular profile of these patients and thus over the years we have gained a much better understanding. However, we really need to understand the immunological profile and the immuno-competence of these patients better. Thus, investigating these patients by utilizing Protagen’s Cancer Immunotherapy Array may enable us to define their immune-profile, so that we can assess their immuno-competence. This will help us, together with the data already collected, to potentially understand why these patients survive for so long and how this can be extrapolated to other patients suffering from glioblastoma."

Dr. Peter Schulz-Knappe, Protagen’s Chief Scientific Officer, commented: "Our unique Cancer Immunotherapy Array has already demonstrated its potential for the prediction of therapeutic response and immune-related adverse events in Immuno-Oncology. The extension into Glioblastoma with a specific view to studying long-term survivors with one of the deadliest tumors provides a great opportunity to apply the Array for the prediction of survival but also to learn more about potential novel pathways for therapeutic intervention. Thus, we believe that applying our technology will result in a better understanding of the immunological profile of these long-term survivors which will benefit all patients suffering from Glioblastoma. We feel privileged that the EORTC Brain Tumor Group shares this vision, and are excited about the collaboration."

On December 4, 2018 Celyad (Euronext Brussels and Paris, and Nasdaq: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell-based therapies, reported updated clinical data for the CYAD-01 program in hematological malignancies presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 60th Annual Meeting (Press release, Celyad, DEC 4, 2018, View Source [SID1234531882]).

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!

THINK Phase 1 Trial Update – Hematological Malignancies

Results from the dose-escalation trial were accepted as an oral presentation at ASH (Free ASH Whitepaper) and presented by Principal Investigator David A. Sallman, M.D., Department of Malignant Hematology at Moffitt Cancer Center (abstracts #902). Interim analysis was reported for ten r/r AML patients across the three dose levels of CYAD-01 without preconditioning.
Out of eight r/r AML patient evaluable per protocol (at least one cycle of treatment) in the dose escalation segment of the trial:
Five patients (62%) showed anti-leukemic activity with three out of eight patients (38%) exhibiting objective response and two patients (25%) exhibiting disease stabilization with relevant bone marrow blasts decrease.
As previously reported, one r/r AML patients achieved a complete response with partial hematological recovery (CRh). This patient was bridged to allotransplant and remains in minimal residual disease negative complete response (CRMRD-) for over 14 months. Two r/r AML patients achieved a complete response with incomplete marrow recovery (CRi) with a duration of one month.
Two r/r AML patients treated at dose level 2 experienced disease stabilization with relevant bone marrow blast decrease. One patient experienced a decrease in blast counts from 9.8% to 5.5% after an initial cycle of CYAD-01. This patient subsequently received a second cycle of CYAD-01 at dose level 2, with the first injection of the second cycle administered seven weeks after the last injection of cycle one. Treatment with a second cycle of CYAD-01 was associated with relevant reduction in bone marrow blast in the patient from 12.5% to 5.8%, which could be considered as an induction of a partial response (PR) post hematological relapse between the two cycles. Further analysis showed both patients achieved CYAD-01 engraftment in the bone marrow at day 28 of treatment.
A sixth r/r AML patient with adverse risk according the 2017 ELN stratification demonstrated a stabilization of disease at two months and is scheduled to initiate a second cycle of CYAD-01.
Only two patients evaluable per protocol progressed in the dose escalation phase of the trial.
Two additional r/r AML patients have been enrolled at dose level 3 of the trial and full results from these patients are anticipated during first half 2019.
CYAD-01 without preconditioning chemotherapy was generally reported to be well-tolerated.
Overall, 14 patients with hematological malignancies (AML, myelodysplastic syndrome and multiple myeloma) treated with CYAD-01 in the trial reached the safety follow -up.
Overall, six patients experienced grade 3/4 treatment-related AEs, which included cytokine release syndrome (CRS), lymphopenia and thrombocytopenia.
CRS occurred in six patients (three grade 1/2 AEs, two grade 3 AEs and one grade 4 AE). Patients experiencing grade 1-3 CRS showed rapid resolution following the appropriate treatment, including tocilizumab.
One r/r AML patient experienced a grade 4 CRS, which was considered a dose-limiting toxicity (DLT), following the first injection of CYAD-01 at dose level 3. The single injection resulted in a reduction of peripheral blast counts from 14% to 4%.
Dr. Christian Homsy, CEO of Celyad, commented, "Preliminary data from 14 patients with relapsed or refractory AML enrolled in the THINK trial have exceeded our expectations with five out of eight patients treated with CYAD-01 without preconditioning demonstrating a relevant anti-leukemic activity. In addition, we are encouraged by the initial safety data that shows CYAD-01 is well-tolerated. We are diligently working to enroll additional patients in our multiple ongoing clinical trials evaluating CYAD-01 in patients with acute myeloid leukemia to better assess this CAR T therapy’s ability to drive a potentially meaningful impact on the treatment of the disease."

DEPLETHINK Phase 1 Trial Update

In October 2018, Celyad enrolled the first patient in the DEPLETHINK Phase 1 trial (NCT03466320). The open-label, dose-escalation trial will evaluate a single injection of CYAD-01 following treatment with the standard preconditioning regimen of cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²), or CyFlu.
The trial includes two different intervals between lymphodepletion and administration of CYAD-01. In addition, the trial will evaluate two dose levels of CYAD-01 including 100 million and 300 million cells per injection, respectively. Following disease assessment at day 35, patients presenting no signs of progression are eligible to receive a cycle of three CYAD-01 injections without preconditioning with two-week intervals at their initial dose levels. The primary endpoint of the trial is safety and secondary endpoints include clinical activity and pharmacokinetics.
As of November 27, 2018, three patients have received an administration of CYAD-01 following preconditioning with CyFlu. Initial data demonstrate that the regimen was well tolerated, with no DLTs nor treatment-related grade 3 or above AEs observed. All three patients were not yet evaluated for clinical response.
Preliminary data from the DEPLETHINK Phase 1 trial are expected in mid-2019.
THINK Phase 1 Trial – Schedule Optimization Cohort 10

The THINK trial was recently amended to add a cohort to assess a more frequent dosing schedule of CYAD-01 for the treatment of r/r AML. The cohort will evaluate six injections of CYAD-01 without preconditioning over two months of administration. The first cycle (induction) will include three injections of CYAD-01 separated by one-week intervals. The second cycle will include three injections of CYAD-01 separated by two-week intervals. All patients in enrolled in the cohort will received 1 billion cells per injection.
Enrollment in the cohort has begun and preliminary data are expected in first half 2019.
EPITHINK Phase 1 Trial Update

The EPITHINK trial is a dose-escalation trial designed to evaluate the administration of CYAD-01 concurrently with 5-azacytidine in treatment-naïve and/or elderly AML patients ineligible for intensive treatment.
As of November 27, 2018, no patients have been enrolled in the trial.
CYAD-01 and THINK Trial Design

CYAD-01 is an investigational CAR-T therapy in which a patient’s T cells are engineered to express the chimeric antigen receptor NKG2D, a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands expressed on tumor cells.

The THINK trial (NCT03018405) is an open-label, dose-escalation Phase 1 trial assessing the safety and clinical activity of multiple CYAD-01 administrations without prior preconditioning in two parallel cohorts: i) patients with hematological malignancies, including r/r AML, and ii) patients with metastatic solid tumors. The dose escalation segment of the study evaluates three dose levels (300 million, 1 billion and 3 billion cells per injection) of one cycle of three CYAD-01 administrations with two-week intervals.

On December 4, 2018 Cellectar Biosciences (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported the initiation of Cohort 6 of its ongoing Phase 1b trial evaluating CLR 131 for the treatment of relapsed/refractory (R/R) multiple myeloma (MM) (Press release, Cellectar Biosciences, DEC 4, 2018, View Source [SID1234531899]). Cohort 6 will evaluate up to four patients with each receiving two doses of 18.75 mCi/m2 of CLR 131 administered one week apart. This fractionated dosing regimen will result in each patient being treated with a total of approximately 75.0 mCi of CLR 131, representing an increase in average total exposure of greater than 15% over Cohort 5.

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!

Cohort 5 also used a fractionated dosing regimen and results showed an ability to administer higher average drug exposure compared with previous cohorts that used bolus dosing. The results seen in Cohort 5 suggest the potential of fractionated dosing to reduce adverse events while improving efficacy. The independent Data Monitoring Committee (DMC) determined the Cohort 5 dose to be safe and well tolerated, and the DMC recommended advancement to the higher dose being used in Cohort 6.

"Cohort 6 builds upon the fractionated dosing we successfully employed with Cohort 5, and we look forward to the results from utilizing a higher drug concentration in this two-dose fractionated approach," said James Caruso, president and chief executive officer of Cellectar Biosciences. "Importantly," Caruso continued, "while cohort 5 showed fewer adverse events than cohort 4, total radiation exposure was greater."

Cohort 5 Results

Results from Cohort 5 indicated enhanced tolerability and safety compared with Cohort 4 despite an 18% increase in total average dose, from 55.29 mCi in Cohort 4 to 65.15 mCi in Cohort 5. Patients in Cohort 5 required less supportive care such as transfusions of platelets or packed red blood cells than seen in previous cohorts.

In addition to the improved safety profile demonstrated in Cohort 5, the company also monitored signals of efficacy. Despite Cohort 5 patients averaging five lines of prior systemic therapies, all patients experienced clinical benefit with two patients achieving minimal responses and two achieving stable disease. Furthermore, looking at surrogate markers, patients in Cohort 5 monitored by M-protein showed a nearly 50% further reduction in M-protein than seen in Cohort 4.

Based on these results and the DMC recommendation, Cellectar plans to modify the single-dose regimen of its ongoing Phase 2 trial of R/R hematologic malignancies to fractionated dosing.

About CLR 131

CLR 131 is Cellectar’s investigational radioiodinated phospholipid ether-drug conjugate (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 relapsed/refractory multiple myeloma (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 as well as a fractionated dose of 15.625 mCi/m2 given twice over seven days in Cohort 5. All study doses and regimens have been deemed safe and well tolerated by an independent Data Monitoring Committee. The company plans to initiate a Phase 1 study with CLR 131 in pediatric solid tumors and lymphoma as well as a second Phase 1 study in combination with external beam radiation for head and neck cancer.

About Phospholipid Drug Conjugates

Cellectar’s product candidates are built upon a patented delivery and retention platform that utilizes optimized PDCs to target cancer cells. The PDC platform selectively delivers diverse oncologic payloads to cancerous cells and cancer stem cells, including hematologic cancers and solid tumors. This selective delivery allows the payloads’ therapeutic window to be modified, which may maintain or enhance drug potency while reducing the number and severity of adverse events. This platform takes advantage of a metabolic pathway utilized by all tumor cell types in all cell cycle stages. Compared with other targeted delivery platforms, the PDC platform’s mechanism of entry does not rely upon specific cell surface epitopes or antigens. In addition, PDCs can be conjugated to molecules in numerous ways, thereby increasing the types of molecules selectively delivered. Cellectar believes the PDC platform holds potential for the discovery and development of the next generation of cancer-targeting agents.

On December 4, 2018 Xspray Pharma AB (Nasdaq First North: XSPRAY) ("Xspray" or the "Company") reported that the United States Patent and Trademark Office (USPTO) has granted a new patent in the United States to Xspray (Press release, Xspray, DEC 4, 2018, View Source [SID1234650104]). The new patent, US 10,143,683, covers the pharmaceutical composition of Xspray’s lead product candidate, HyNap-Dasa. This is Xspray’s third product patent in the US which is Xspray’s main market. The new patent will expireJanuary 11, 2033.
"This new patent approval in our most important market further confirms our innovative development work. Together with the previously communicated formal clinical bioequivalence for the company´s lead product candidate, HyNap-Dasa, this patent will be instrumental in our forthcoming negotiations with potential partners," says Per Andersson, CEO of Xspray.

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!

Xspray strives to obtain patents both for composition and methodology, and this new patent claims an amorphous solid dispersion (pharmaceutical composition) of dasatinib.

"The new patent for HyNap-Dasa has the broadest scope of all our composition patents in the US and makes it significantly more difficult for other companies to launch a dasatinib product based on amorphous solid dispersion formulation in the US market during the lifetime of this patent, i.e. up until 2033", says Per Andersson, CEO of Xspray.