On December 5, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported new results from three key studies of IMBRUVICA (ibrutinib) in chronic lymphocytic leukaemia (CLL), a difficult-to-treat form of blood cancer and the most common form of leukaemia in adults (Press release, Johnson & Johnson, DEC 5, 2018, View Source [SID1234531913]).1 Findings were presented at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place in San Diego, CA.

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Results from the National Cancer Institute (NCI)-sponsored Phase 3 study (E1912) led by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) were presented during the Late-Breaker abstract oral session. The study evaluated ibrutinib plus rituximab compared to a chemotherapy regimen of fludarabine, cyclophosphamide, and rituximab (FCR) in previously untreated patients aged 70 years or younger with CLL. With nearly three years of follow-up, the data showed ibrutinib plus rituximab significantly prolonged progression-free survival (PFS) and overall survival (OS) versus FCR.2

Data from the Phase 3 iLLUMINATE (PCYC-1130) study were also presented in an oral session and simultaneously published in The Lancet Oncology. Findings showed the combination of ibrutinib plus obinutuzumab significantly improved PFS versus chlorambucil plus obinutuzumab in patients with newly diagnosed CLL.3 These data recently supported the submission of a Type II variation application to the European Medicines Agency (EMA), seeking approval for the expanded use of ibrutinib in combination with obinutuzumab in previously untreated adults with CLL.

In addition, ibrutinib data from the Phase 1b/2 study and its extension study (PCYC-1102, PCYC-1103) with up to seven years of follow-up in patients with newly diagnosed and relapsed/refractory (R/R) CLL, demonstrated durable, long-term survival benefits as a monotherapy, representing the longest follow-up for a Bruton’s tyrosine kinase (BTK) inhibitor in CLL.4

"Findings from both iLLUMINATE and the ECOG-ACRIN study demonstrate impressive prolonged progression-free survival for the relevant ibrutinib-based combinations, versus commonly used chemo-immunotherapy regimens," said Dr Carol Moreno, Consultant Haematologist, Hospital de la Santa Creu Sant Pau, Autonomous University of Barcelona, Barcelona, Spain. "These non-chemotherapy regimens present an advance in how we might consider the management of patients, including younger patients and those with high risk CLL features with potential to address the trade-off between efficacy and toxicity for patients."

"The data presented at ASH (Free ASH Whitepaper) provide further convincing evidence of the clinical benefit ibrutinib can offer to patients across the spectrum of CLL management. The long-term data also offer confidence of its sustained activity for patients," said Dr Catherine Taylor, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag Limited. "We continue to explore the full potential of ibrutinib through a comprehensive clinical development programme, to improve outcomes and change what a blood cancer diagnosis means to patients."

Ibrutinib, a first-in-class BTK inhibitor, is jointly developed and commercialised by Janssen Biotech, Inc., and Pharmacyclics LLC, an AbbVie company.

Results From the Randomised Phase 3 Study of Ibrutinib (PCI-32765)-Based Therapy vs. FCR Chemoimmunotherapy in Untreated Younger Patients with CLL: A Study of the ECOG-ACRIN Cancer Research Group (E1912) (Abstract #LBA-4)

With a median follow-up of 33.4 months, the interim analysis observed 77 PFS events and 14 deaths. Ibrutinib plus rituximab significantly improved PFS compared to FCR (HR: 0.352; 95 percent confidence interval [CI]: 0.223-0.558; p<0.0001); the pre-specified boundary for PFS was crossed. The ibrutinib plus rituximab treatment arm also showed improved OS (HR: 0.168; 95 percent CI: 0.053-0.538; p=0.0003, pre-specified boundary for superiority p=0.0005).2

In a subgroup analysis for PFS, ibrutinib plus rituximab showed prolonged PFS independent of age, sex, performance status, disease stage, or the presence/absence of the cytogenetic abnormality, deletion 11q23. With current follow-up, ibrutinib plus rituximab was also superior to FCR for IGHV unmutated patients (HR: 0.262; 95 percent CI: 0.137-0.498; p<0.0001) but not IGHV mutated patients (HR: 0.435; 95 percent CI: 0.140-0.1350; p=0.07).2

Grade 3/4 treatment-related adverse events (AEs) were observed in 58 percent of ibrutinib plus rituximab treated patients and 72 percent of FCR treated patients (p=0.0042). FCR was more frequently associated with Grade 3 and 4 neutropenia (FCR: 44 percent vs. ibrutinib plus rituximab: 23 percent; p<0.0001) and infectious complications (FCR: 17.7 percent vs. ibrutinib plus rituximab: 7.1 percent; p<0.0001).2

Results from the Phase 3 iLLUMINATE study (Abstract #691)

At a median follow-up of 31.3 months, ibrutinib plus obinutuzumab significantly prolonged the Independent Review Committee (IRC)-assessed PFS compared with chlorambucil plus obinutuzumab (median not reached [NR] vs. 19.0 months; HR 0.231; 95 percent CI: 0.145-0.367; p<0.0001), with a 77 percent reduction in risk of progression or death.3

Superior PFS in the ibrutinib plus obinutuzumab arm compared to the chlorambucil plus obinutuzumab arm was also seen in the high-risk population, including those with unmutated IGHV, del11q, del17p and/or TP53 mutation, with an 85 percent reduction in risk of progression or death (median NR vs. 14.7 months; HR 0.154; 95 percent CI: 0.087-0.270; p<0.0001).5 In addition, IRC-assessed overall response rate (ORR) was higher in the ibrutinib plus obinutuzumab arm versus the chlorambucil plus obinutuzumab arm (88 percent vs. 73 percent); complete response (CR)/complete response with incomplete blood recovery (CRi) rates were also higher with 19 percent versus eight percent, respectively. Minimal residual disease (MRD) was undetectable in blood and/or bone marrow (<10-4 by flow cytometry) for 35 percent of patients treated with ibrutinib plus obinutuzumab, compared to 25 percent of patients treated with chlorambucil plus obinutuzumab. OS rates at 30 months were 86 percent for the ibrutinib plus obinutuzumab arm compared to 85 percent for the chlorambucil plus obinutuzumab arm.3

The most common Grade 3 or higher AEs in the ibrutinib plus obinutuzumab arm versus chlorambucil plus obinutuzumab arm were neutropenia (36 percent vs. 46 percent), thrombocytopenia (19 percent vs. 10 percent), pneumonia (7 percent vs. 4 percent), atrial fibrillation (5 percent vs. 0 percent), febrile neutropenia (4 percent vs. 6 percent), anaemia (4 percent vs. 8 percent) and infusion-related reactions (IRRs; 2 percent vs. 8 percent).5 No patients discontinued obinutuzumab due to IRRs in the ibrutinib plus obinutuzumab arm compared to the chlorambucil plus obinutuzumab arm (6 percent). AEs led to the discontinuation of ibrutinib in 16 percent of patients and led to the discontinuation of chlorambucil in nine percent of patients. AEs led to the discontinuation of obinutuzumab in the ibrutinib plus obinutuzumab arm (9 percent) and chlorambucil plus obinutuzumab arm (13 percent). With about three years of follow-up, 70 percent of patients in the ibrutinib plus obinutuzumab arm remain on ibrutinib monotherapy.3

Results from up to seven years of follow-up in the Phase 1b/2 PCYC-1102 study and its extension, PCYC-1103 (Abstract #3133)

Results from these studies showed durable efficacy of ibrutinib in newly diagnosed and R/R CLL patients. These long-term data showed sustained PFS and OS rates. The estimated seven-year PFS rates were 80 percent for patients with newly diagnosed disease and 32 percent for patients with R/R disease. Notably, administering ibrutinib in earlier lines of therapy resulted in improved PFS outcomes for R/R patients.4

ORR was 89 percent for all patients (CR, 15 percent), with similar rates in newly diagnosed (87 percent [CR, 32 percent]) and R/R CLL patients (89 percent [CR, 10 percent]). Median duration of response (DOR) was NR (95 percent CI: 0+-85+) for newly diagnosed CLL patients and was 57 months (95 percent CI: 0+-85+) for R/R CLL patients.6 Median PFS was NR (95 percent CI: not estimable [NE], NE) for newly diagnosed CLL patients and was 51 months (95 percent CI: 37-70) for R/R CLL patients.4,6 The median OS was NR in newly diagnosed (95 percent CI: 80-NE) or R/R CLL patients (95 percent CI: 63-NE), with estimated seven-year OS rates of 75 percent and 52 percent, respectively.4

Grade 3 or higher AEs were reported in 74 percent of newly diagnosed and 89 percent of R/R patients with CLL. Hypertension (newly diagnosed, 32 percent; R/R, 26 percent), diarrhoea (newly diagnosed, 16 percent; R/R, 4 percent), and hyponatraemia (newly diagnosed, 10 percent; R/R, 0 percent) were among the most common Grade 3 or higher treatment-emergent AEs. Major haemorrhage and Grade 3 or higher atrial fibrillation, thrombocytopenia, anaemia, and arthralgia were observed in 11 percent or less of newly diagnosed and R/R patients. In addition, infection (newly diagnosed, 23 percent; R/R, 55 percent) was more common in R/R CLL patients.6 No new or unexpected AEs were observed, and the occurrence of most Grade 3 or higher AEs and serious AEs decreased over time, with the exception of hypertension.6

#ENDS#

About the ECOG-ACRIN E1912 study

The Phase 3 study (E1912) evaluated previously untreated patients with CLL aged 70 years or younger, who were randomly assigned to receive ibrutinib (420 mg/day until disease progression) and rituximab (50 mg/m2 on day 1 of cycle 2; 325 mg/m2 on day 2 of cycle 2; 500 mg/m2 on day 1 of cycles 3-7) (n=354) or six courses of intravenous fludarabine (25 mg/m2) and cyclophosphamide (250 mg/m2) days 1-3 with rituximab (50 mg/m2 on day 1 of cycle 1; 325 mg/m2 on day 2 of cycle 1; 500 mg/m2 on day 1 of cycles 2-6) every 28-days (n=175). The primary endpoint was PFS with a secondary endpoint of OS.2

The federally funded study was designed by researchers with ECOG-ACRIN. It was conducted through the NCI’s National Clinical Trials Network. Pharmacyclics LLC provided ibrutinib under a cooperative research and development agreement with NCI and a separate agreement with ECOG-ACRIN.

About the iLLUMINATE study

iLLUMINATE (PCYC-1130) evaluated newly diagnosed CLL patients who were randomised to receive ibrutinib 420 mg once-daily continuously until disease progression or unacceptable toxicity in combination with obinutuzumab 1000 mg intravenously over six cycles (n=113); or chlorambucil on Days 1 and 15 of each cycle plus obinutuzumab 1000 mg intravenously over 6 cycles (n=116). Median age of the patients was 71 years and 65 percent of the patients had high-risk genomic features. The primary endpoint was PFS, as assessed by an Independent Review Committee. Secondary endpoints included PFS in a high-risk population, rate of undetectable MRD, ORR, OS, and safety.3

About PCYC-1102 and PCYC-1103

With up to seven years of follow-up, the studies (Phase 1b/2, PCYC-1102 and its extension, PCYC-1103) evaluated newly diagnosed and R/R CLL patients (n=132; newly diagnosed=31, R/R=101), including those with high-risk features, who received 420 mg or 840 mg once-daily ibrutinib until disease progression or unacceptable toxicity. As of the cutoff, 55 percent of newly diagnosed and 21 percent of R/R patients continued ibrutinib, with median follow-up of 67 months.4

About ibrutinib

Ibrutinib is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, which works by forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B-cells.7 By blocking this BTK protein, ibrutinib helps kill and reduce the number of cancer cells, thereby delaying progression of the cancer.8

Ibrutinib is currently approved in Europe for the following uses:9

Chronic lymphocytic leukaemia (CLL): As a single agent for the treatment of adult patients with previously untreated CLL, and as a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy.
Mantle cell lymphoma (MCL): Adult patients with relapsed or refractory mantle cell MCL.
Waldenström’s macroglobulinemia (WM): Adult patients who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemo-immunotherapy.
Ibrutinib is approved in more than 90 countries, and, to date, has been used to treat more than 135,000 patients worldwide across its approved indications.10

The most common adverse reactions seen with ibrutinib include diarrhoea, neutropenia, haemorrhage (e.g., bruising), musculoskeletal pain, nausea, rash, and pyrexia.9

For a full list of side effects and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics for further information.

On December 5, 2018 Janssen pharmaceutical companies at Johnson & Johnson reported the results of the MAIA phase 3 study, which shows that the addition of daratumumab to lenalidomide and dexamethasone (Rd) significantly reduced the risk of progression of the disease or death in patients with recently diagnosed multiple myeloma who are not suitable for autologous stem cell transplantation (ASCT) ( abstract # LBA-2 ) (Press release, Johnson & Johnson, DEC 5, 2018, View Source [SID1234531914]). 1 These data were presented during the oral session of last-minute last-minute summaries at the 60th annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, California.

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"The Phase 3 MAIA study reinforces the clinical profile of daratumumab in combination with a standard treatment regimen for newly diagnosed patients with multiple myeloma who are not eligible for transplantation," states Thierry Facon, MD, Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France and principal investigator. "The positive data show the potential role of daratumumab in combination with lenalidomide and dexamethasone as a new important therapeutic approach for this patient population."

At a mean follow-up of 28 months, data from the phase 3 MAIA study showed that daratumumab in combination with Rd significantly reduced the risk of progression or death of the disease by 44 percent in newly diagnosed multiple myeloma patients who are not fit for transplantation, compared to treatment with Rd alone (hazard ratio [HR] = 0.56, 95% confidence interval [CI]: 0.43-0.73, p <0.0001). 1 The median progression free survival (PFS) for daratumumab-Rd has not yet been achieved, compared to 31.9 months for patients who received Rd alone. oneThe incorporation of daratumumab resulted in deeper responses with respect to Rd alone, including increased rates of complete response (CR) or higher (48 percent vs. 25 percent) and improved rates of very good partial response (VGPR) or better (79 percent, versus 53 percent). 1 Daratumumab-Rd induced a 3-fold higher rate of negativity to minimal residual disease (MRD) compared to those who received Rd alone (24 percent vs. 7 percent). one

"Estos datos subrayan el perfil clínico estable observado en los pacientes recién diagnosticados con mieloma múltiple que reciben terapia con daratumumab, incluso para aquellos que no son aptos para el trasplante", comenta la Dra. Catherine Taylor, directora del área de terapia hematológica para Europa, Oriente Medio y África (EMEA) de Janssen-Cilag Limited. "Es el tercer estudio en pacientes recientemente diagnosticados que ha alcanzado su principal criterio de evaluación y esperamos continuar proporcionando avances innovadores a pacientes con mieloma múltiple a través de nuestro robusto programa de investigación clínica, que cuenta con el potencial de revolucionar el tratamiento del cáncer atacando a la enfermedad en sus etapas más tempranas", añade Taylor.

The most common grade 3/4 adverse events arising from treatment (TEAE) for daratumumab-Rd (≥ 10 percent) included neutropenia (50 percent), lymphopenia (15 percent), pneumonia (14 percent), and anemia (12 percent). 1 Infusion-related reactions (RRI) occurred in 41 percent of patients, of whom only 3 percent were grade 3/4. 1 The incidence of invasive secondary neoplasms was 3 percent in the daratumumab-Rd group, compared to 4 percent with Rd alone. 1 TEAEs with a death result were 7 percent in the daratumumab group, compared to 6 percent in the Rd group.1 The safety profile of daratumumab was in line with that of previous studies. one

These data will support a future marketing authorization request for daratumumab in combination with Rd for this patient population.

#FINISH#

About the MAIA 1 trial

The randomized, open-label, multi-center phase 3 study included 737 newly diagnosed patients with multiple myeloma unsuitable for high-dose chemotherapy and ASCT between 45 and 90 years (mean age 73). Patients were randomly assigned to receive daratumumab-Rd or Rd only in cycles of 28 days. In the daratumumab-Rd treatment group, patients received IV daratumumab 16 milligrams per kilogram (mg / kg) weekly for cycles 1 – 2, every two weeks for cycles 3-6 and every 4 weeks for cycle 7 and later. Patients in the daratumumab-Rd and Rd treatment group received 25 mg of lenalidomide on days 1 – 21 of each 28-day cycle and dexamethasone at 40 mg once per week for each cycle.

About daratumumab

Daratumumab is a first-generation biologic drug against the CD38 antigen, a protein that is expressed at high levels on the surface of multiple myeloma tumor cells, regardless of the stage of the disease. 2 Daratumumab induces rapid death of cancer cells through multiple immunologically mediated mechanisms of action, including complementary cytotoxicity (CDC), cellular cytotoxicity by antibody dependence (ADCC), cellular phagocytosis by antibody dependence (ADCP) and apoptosis , in which a series of molecular steps in a cell leads to its death. 3 Daratumumab also reduced a subset of suppressor cells of myeloid origin (CD38 + MDSCs), CD38 + T regulatory cells (Tregs) and CD38 + B (Bregs). 3 Currently daratumumab is under study through a comprehensive clinical development program on different treatments for multiple myeloma, including parameters such as first-line treatment and relapse. 4,5,6,7,8,9,10,11 Likewise, there are additional studies in progress or planned in order to study their potential in malignant or premalignant hematological diseases in which the CD38 protein is expressed, such as latent myeloma. . 12-13 For more information, see www.clinicaltrials.gov.

In Europe, daratumumab is currently indicated for use in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for an autologous stem cell transplant, whose previous treatment included an inhibitor of the proteasome and an immunomodulatory agent, and that they would have demonstrated a progression of the disease in the last treatment and in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one previous therapy 3 . For more information on daratumumab, see the Summary of Product Characteristics inView Source .

In August 2012 , Janssen Biotech, Inc. and Genmab A / S signed a worldwide agreement that awarded Janssen an exclusive license to develop, manufacture and market daratumumab. 14

About multiple myeloma

Multiple myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells. 15 In 2016, more than 45,000 new cases were diagnosed in Europe and more than 29,000 patients died 16 . Up to half of the patients with a recent diagnosis do not reach the five-year survival rate 17 and almost 29% of the patients with MM will die within one year of diagnosis. 18

Although treatment may result in remission, unfortunately, most patients will most likely relapse as there is currently no cure. 19 Refractory multiple myeloma occurs when the disease progresses within 60 days of the last therapy. 20,21 Recurrent cancer occurs when the disease returns after a period of initial, partial or complete remission. 22 While some patients with MM have no symptoms at all, most patients are diagnosed due to symptoms that may include bone problems, low blood counts, elevated calcium, kidney problems, or infections. 2. 3 Patients who relapse after treatment with standard therapies, including PIs and immunomodulatory agents, have a poor prognosis and few treatment options are available. 24

On December 5, 2018 iCell Gene Therapeutics, LLC reported results from a study ongoing at Chengdu Military General Hospital of ICG144, the first CLL1-CD33 Compound CAR T-cell (cCAR) in clinical study, in patients with particularly difficult to treat Acute Myeloid Leukemia (AML) (Press release, iCell Gene Therapeutics, DEC 5, 2018, View Source [SID1234531930]). Patients 1 and 2 both failed multiple previous cycles of therapy and presented with complex conditions limiting further options. Treatment with CLL1-CD33 cCAR led both patients to complete response and engraftment of haploidentical stem cell transplantation (allo-HSCT) without myeloablative conditioning.

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"Patient response seen to date is encouraging for refractory AML patients, and opens the potential of this novel therapy as bridge to transplant, a supplement to chemotherapy, or as a standalone therapy for patients with acute myeloid leukemia." stated Dr. Fang Liu, MD, PhD, the Principal Investigator of the study who presented the results at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego. Dr. Yupo Ma, MD, PhD, Chairman of iCell Gene Therapeutics added, "Initial patient experience highlights the potential importance of iCell’s proprietary multiple antigen targeting and enhancing technologies to overcome antigen escape and improve treatment outcomes."

Upon enrollment, patients receive a lymphodepletion regimen consisting of fludarabine and cyclophasphamide followed by 1×106 – 2×106 CAR T cells/kg, nonmyeloablative conditioning and Haplo-HSCT

Patient 1 is a 6-year-old originally diagnosed with Franconi anemia transformed JMML and eventually to AML-M5 with more than 90% blasts in the marrow, complex karyotype and FLT3-ITD mutation.
Patient 2 is a 23-year-old, failed to TKIs, AP-CML (basophils>20%, plt>1000X109/L), T315I mutation.
Complete response and Haplo-HSCT engraftment was observed in both patients.
Grade 1 CRS and pancytopenia was observed in both patients.
Grade 3 neurotoxicity was observed in Patient 1.
About CLL1-CD33 cCAR T cell therapy

CLL1-CD33 cCAR is a compound Chimeric Antigen Receptor (cCAR) immunotherapy with two distinct functional CAR molecules expressed on a T-cell, directed against the surface proteins CLL1 and CD33. The diseases treated by CLL1-CD33 cCAR could include acute myeloid leukemia, myelodysplastic syndromes, chronic myeloid leukemia and chronic myeloproliferative neoplasms. CLL1 is associated with leukemia stem cells and disease relapse, while CD33 is expressed on bulky AML disease. Treatment of AML is a challenge due to heterogeneity of AML bearing cells, which renders single antigen targeting CAR T-cell therapy ineffective. ICG144 cCAR is designed to target the mechanisms of single-CAR relapse, specifically antigen escape and leukemic stem cells.

About AML

Acute myeloid leukemia (AML) is the abnormal proliferation of immature myeloid cells and the most common leukemia in adults. Prognosis is dismal when AML relapses or is refractory to chemotherapy. Mortality associated with this disease is high, with approximately 10,000 deaths in 2018 in the US.

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.

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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]).

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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."