On December 10, 2018 Janssen pharmaceutical companies at Johnson & Johnson reported new results from three key studies of IMBRUVICA (ibrutinib) in chronic lymphocytic leukemia (CLL), a form of difficult blood cancer treat and the most common form of leukemia in adults (Press release, Johnson & Johnson, DEC 10, 2018, View Source [SID1234531991]). 1 The findings were presented at the 60th to annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) held in San Diego (California).

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The results of the phase 3 study sponsored by the National Cancer Institute (NCI) (E1912), led by the ECOG-ACRIN cancer research group, were presented during the last oral summary session. The study evaluated the combination of ibrutinib plus rituximab compared to a regimen for chemotherapy of fludarabine, cyclophosphamide, and rituximab (FCR) in patients 70 years of age or younger with CLL who had not received prior treatment. After almost three years of follow-up, the data showed that ibrutinib plus rituximab significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to the FCR combination. two

The iLLUMINATE (PCYC-1130) Phase 3 data was also presented in an oral session and simultaneously published in The Lancet Oncology . The results showed that the combination of ibrutinib plus obinutuzumab significantly improved progression-free survival versus the combination of chlorambucil and obinutuzumab in patients with newly diagnosed CLL. 3 These data recently supported the submission of a Type II variation request to the European Medicines Agency (EMA), which seeks approval to expand the use of ibrutinib in combination with obinutuzumab in adults with CLL who have not received prior treatment.

In addition, the 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 CLL and relapsed / recurrent (R / R) , showed long-term survival benefits as monotherapy, which implies the longer follow-up of a Bruton tyrosine kinase inhibitor (BTK) in CLL. 4

"The results of the iLLUMINATE and ECOG-ACRIN studies show an impressive survival without prolonged progression for the relevant combinations based on ibrutinib, compared to the regimens of chemoimmunotherapy usually used," said Dr. Carol Moreno, a hematologist at the Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona (Spain). "These non-chemotherapeutic regimens represent an advance in the way we might consider treating patients, including the youngest and those with high risk characteristics in CLL, with potential to address the compromise between efficacy and toxicity for patients. »

"The data presented in the ASH (Free ASH Whitepaper) provide more convincing evidence of the clinical benefit that ibrutinib can offer to patients across the spectrum of CLL treatment. The long-term data also offer reliability in terms of sustained activity for patients, "explained Dr. Catherine Taylor, head of the area of ​​hematology therapy in Europe, Middle East and Africa (EMEA) of Janssen-CilagLimited. "We continue to explore the full potential of ibrutinib through a comprehensive clinical development program, in order to improve the results and change what the diagnosis of blood cancer means for patients."

JanssenBiotech, Inc. and PharmacyclicsLLC, an AbbVie company, jointly develop and market ibrutinib, a first-class BTK inhibitor.

Results of the randomized phase 3 study of ibrutinib treatment (PCI-32765) versus chemoimmunotherapy with CRF in younger patients with CLL who were not previously treated: a study by the ECOG-ACRIN cancer research group (E1912) ( summary No. LBA-4 )

With an average follow-up of 33.4 months, the provisional analysis observed 77 cases of progression-free survival and 14 deaths. The combination of ibrutinib plus rituximab significantly improved progression-free survival compared to the FCR combination (hazard ratio: 0.352, 95% confidence interval [CI]: 0.223-0.558, p <0.0001); the pre-established limit for survival without progression was crossed. The treatment group of ibrutinib plus rituximab also showed an improvement in overall survival (hazard ratio: 0.168, 95% CI: 0.053-0.538, p = 0.0003, pre-established upper limit p = 0.0005). two

In a progression-free survival subgroup analysis, the combination ibrutinib plus rituximab showed a prolonged progression-free survival independent of age, sex, functional status, disease phase or the presence / absence of cytogenetic abnormalities, 11q23 deletion. With the current follow-up, the ibrutinib plus rituximab combination was also superior to the FCR combination in patients who did not have mutations in IGHV (risk ratio: 0.262, 95% CI: 0.137-0.498, p <0.0001) but not in patients who presented mutations in IGHV (hazard ratio: 0.435, 95% CI: 0.140-0.1350, p = 0.07). two

Adverse reactions associated with grade 3/4 treatment were observed in 58% of patients treated with the combination ibrutinib plus rituximab, and in 72% of patients treated with HRG (p = 0.0042). The FCR combination was more frequently associated with grade 3 and 4 neutropenia (FCR: 44% versus the combination ibrutinib plus rituximab: 23%, p <0.0001) and infectious complications (FCR: 17.7% vs. the combination ibrutinib plus rituximab: 7.1%, p <0.0001). two

Results of the 3 phase iLLUMINATE study ( summary # 691 )

At an average follow-up of 31.3 months, the combination of ibrutinib plus obinutuzumab significantly prolonged progression-free survival as assessed by the Independent Review Committee (ICR), compared with the combination of chlorambucil and obinutuzumab (average not reached versus 19, 0 months, risk ratio 0.231, 95% CI: 0.145-0.367, p <0.0001), with a 77% reduction in the risk of progression or death. 3

High progression survival was also observed in the ibrutinib plus obinutuzumab combination group compared to the combination of chlorambucil plus obinutuzumab, even in those patients who had mutations in IGHV, del11q, del17p and / or TP53, with an 85% reduction in the risk of progression or death (average not reached versus 14.7 months, risk ratio 0.154, 95% CI: 0.087-0.270, p <0.0001). 5 In addition, the overall response rate (ORR) assessed by the IRC was higher in the ibrutinib plus obinutuzumab group compared to the chlorambucil plus obinutuzumab group (88% versus 73%); Complete response (CR) / complete response with incomplete blood recovery (CRi) rates were also higher, with 19% versus 8%, respectively. No minimal residual disease (MRE) was detected in the blood and / or spinal cord (<10 -4by flow cytometry) in 35% of patients treated with ibrutinib plus obinutuzumab, compared to 25% of patients treated with chlorambucil plus obinutuzumab. Overall survival rates at 30 months were 86% for the ibrutinib plus obinutuzumab group, versus 85% for the chlorambucil plus obinutuzumab group. 3

The most common adverse events of grade 3 or higher in the ibrutinib plus obinutuzumab group versus the chlorambucil plus obinutuzumab group were neutropenia (36% vs. 46%), thrombocytopenia (19% vs. 10%), pneumonia (7% vs. 4%), atrial fibrillation (5% vs. 0%), febrile neutropenia (4% vs. 6%), anemia (4% vs. 8%), and perfusion-related reactions (IRR, 2% vs 8%). %). 5No patient discontinued treatment with obinutuzumab due to infusion-related reactions in the ibrutinib plus obinutuzumab combination group, compared with the chlorambucil plus obinutuzumab group (6%). Adverse reactions continue to cause the interruption of ibrutinib treatment in 16% of patients and involves the interruption of chlorambucil intake in 9% of patients. Adverse reactions caused the interruption of treatment with obinutuzumab in the group of ibrutinib plus obinutuzumab (9%) and in the group of chlorambucil plus obinutuzumab (13%). With an approximate follow-up of three years, 70% of the patients in the ibrutinib plus obinutuzumab group continued on monotherapy with ibrutinib.3

Results of up to seven years of follow-up in the PCYC-1102 phase 1b / 2 study and its extension, PCYC-1103 ( abstract number 3133 )

The results of these studies demonstrated a lasting efficacy of ibrutinib in patients with recently diagnosed or relapsing / recurrent CLL. These long-term data showed sustained overall progression-free survival and response rates. The estimated 7-year progression-free survival rates were 80% for patients with newly diagnosed disease, and 32% for patients with recurrent / relapsing disease. In particular, the administration of ibrutinib in earlier lines of therapy resulted in improved progression-free survival outcomes in relapsed / recurrent patients. 4

The overall response rate was 89% for all patients (complete response, 15%) with similar rates in patients with recently diagnosed CLL (87% [complete response, 32%] and relapsed / recurrent (89% [response complete, 10%]) The average response duration (DOR) (95% CI: 0 + -85 +) was not reached in the newly diagnosed CLL patients and was 57 months (95% CI: 0+ . -85+) for CLL patients relapsed / recurrent 6 survival was not reached average progression (95% IC: not estimable [NE], NE) for CLL patients newly diagnosed was 51 months (95% CI: 37-70) for relapsed / recurrent CLL patients 4.6 The average general response was not reached in patients with recently diagnosed CLL (95% CI: 80-NE) or relapsed / recurrent (95% CI: 63-NE), with estimated overall response rates at seven years of 75% and 52%, respectively. 4

Grade 3 or higher adverse reactions were recorded in 74% of patients with recently diagnosed CLL and in 89% of relapsed / recurrent patients. Among the most common adverse reactions of grade 3 or higher that arose with treatment are hypertension (recent diagnosis, 32%, relapse / recurrent, 26%), diarrhea (recent diagnosis, 16%, relapse / recurrent, 4%) and hyponatremia (recent diagnosis, 10%; relapse / recurrent, 0%). In 11% or less of newly diagnosed or relapsed / recurrent patients, significant bleeding and grade 3 or higher articular fibrillation, thrombocytopenia, anemia, and arthralgia were detected. In addition, infections (recent diagnosis, 23%; relapse / recurrent,6 No new or unexpected adverse reactions were observed and the prevalence of most of the adverse reactions of grade 3 or higher and severe decreased with time, except hypertension. 6

#FINISH#

About the ECOG-ACRIN E1912 study

The phase 3 study (E1912) evaluated patients with CLL aged 70 years or younger who had not received previous treatment and who had been randomly assigned to receive ibrutinib (420 mg / day until disease progression) and rituximab (50 mg / m 2 on day 1 of cycle 2, 325 mg / m 2 on day 2 of cycle 2, 500 mg / m 2 on day 1 of cycles 3-7) (n = 354) or six stages of fludarabine intravenous (25 mg / m 2 ) and cyclophosphamide (250 mg / m 2 ) days 1-3 with rituximab (50 mg / m 2 on day 1 of cycle 1; 325 mg / m 2 on day 2 of cycle 1; 500 mg / m 2on day 1 of cycles 2-6) every 28 days (n = 175). The primary endpoint was survival without progression with a secondary criterion of overall survival. two

The study, financed with federal funds from the US UU., Was designed by researchers together with ECOG-ACRIN. It was conducted in the NCI national clinical trials network. PharmacyclicsLLC provided ibrutinib under a research and development cooperation agreement with the NCI and an independent agreement with ECOG-ACRIN.

About the iLLUMINATE study

iLLUMINATE ( PCYC-1130) evaluated newly diagnosed patients with CLL who were randomized to receive ibrutinib 420 mg once a day continuously until disease progression or unacceptable toxicity in combination with obinutuzumab 1000 mg intravenously for six cycles (n = 113 ); or chlorambucil on days 1 and 15 of each cycle plus obinutuzumab 1000 mg intravenously for 6 cycles (n = 116). The average age of the patients was 71 years and 65% of the patients presented high-risk genomic characteristics. The primary endpoint was survival without progression, assessed by an Independent Review Committee.3

About PCYC-1102 and PCYC-1103

With a follow-up of up to seven years, the studies (phase 1b / 2, PCYC-1102 and its extension, PCYC-1103 ) evaluated patients with newly diagnosed CLL and relapsed / recurrent (n = 132; newly diagnosed = 31; relapse / recurrent = 101), including those with high-risk characteristics, who received 420 mg or 840 mg once daily of ibrutinib until disease progression or unacceptable toxicity. At the deadline, 55% of newly diagnosed patients and 21% of relapsed / recurrent patients continued to take ibrutinib, with an average follow-up of 67 months. 4

About ibrutinib

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

Currently, ibrutinib is authorized in Europe for the following uses: 9

chronic lymphocytic leukemia (CLL): As a single agent for the treatment of adult patients with CLL who have not undergone previous treatment, and as a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received less a previous treatment.
Mantle cell lymphoma (MCL): Adult patients with relapsed / recurrent MCL.
Waldenström macroglobulinemia (MW): Adult patients who have received at least one previous treatment or first-line treatment for patients not suitable for chemoimmunotherapy.
Ibrutinib is approved in more than 90 countries and, to date, it has been used to treat more than 135,000 patients worldwide for its approved indications. 10

The most common adverse reactions observed with ibrutinib are diarrhea, neutropenia, haemorrhage (eg, bruising), musculoskeletal pain, nausea, rash, and pyrexia. 9

Consult the summary of product characteristics for a complete list of side effects and information on dosing and administration, contraindications and other precautions when taking ibrutinib.

On December 10, 2018 Blue Earth Diagnostics, a molecular imaging diagnostics company, reported that the U.S. Food and Drug Administration (FDA) has accepted for review a supplemental New Drug Application (sNDA) for the expanded use of Axumin (fluciclovine F 18) in adults for the detection and continuing assessment of glioma (Press release, Blue Earth Diagnostics, DEC 10, 2018, View Source [SID1234531990]).

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Fluciclovine is a synthetic amino acid labeled with the radioisotope F 18, enabling PET imaging to visualize the increased amino acid transport that occurs in malignant tumors such as glioma, which is a serious and life-threatening condition accounting for about 80% of all malignant brain tumors.

18F-Fluciclovine, under the tradename Axumin (fluciclovine F 18) injection, is FDA-approved for use in positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood levels of prostate specific antigen (PSA) following prior treatment. 18F-Fluciclovine PET imaging is being investigated for the detection and continuing assessment of glioma. (For additional product information please see the end of this news release.) 18F-Fluciclovine has previously been granted Orphan Drug status by both the FDA and the European Medicines Agency for the diagnosis of glioma.

"We are very pleased that the FDA has accepted for review our sNDA submission for the use of 18F-fluciclovine PET imaging in glioma," said Jonathan Allis, D. Phil., CEO of Blue Earth Diagnostics. "Expanding the label for Axumin is part of our mission to develop and commercialize innovative PET imaging products that address unmet medical needs for patients with cancer."

"Glioma is the twelfth leading cause of death from cancer, and certain aggressive forms of the disease, such as glioblastoma multiforme, can progress rapidly," said Peter Gardiner, MB ChB, MRCP, FFPM, CMO of Blue Earth Diagnostics. "Physicians need precise information about the location and extent of the tumor to help guide surgical procedures and radiation therapy, as well as for subsequent continued assessment and monitoring of the disease. We are exploring the potential utility of 18F-fluciclovine PET to assist them in these efforts."

Blue Earth Diagnostics recently announced results from one of the Phase 3 clinical trials supporting the sNDA submission to the FDA at the Society for Neuro-Oncology annual meeting in November 2018. The study, BED006, was a prospective, blinded image evaluation that examined the diagnostic performance of 18F-fluciclovine PET imaging, in conjunction with various types of MRI, for imaging of suspected glioma when interpreted by readers unfamiliar with 18F-fluciclovine PET. Results indicated a Positive Predictive Value (PPV) of more than 90% for each of the three blinded readers and consistent image interpretation across these readers. In addition, 18F-fluciclovine PET with MRI (CE-T1W MRI) identified additional regions suspicious for glioma that MRI alone was unable to identify, which subsequent biopsies confirmed as malignant. To date, the safety profile of 18F-fluciclovine PET imaging in patients with glioma appears to be consistent with that summarized in the current Axumin U.S. prescribing information.

About 18F-fluciclovine PET in Glioma

18F-Fluciclovine PET is a diagnostic imaging radiopharmaceutical for PET imaging that consists of a synthetic amino acid labeled with the radioisotope F 18, enabling the visualization of the increased amino acid transport that occurs in malignant tumors. 18F-Fluciclovine, under the trade name Axumin, is approved by the U.S. Food and Drug Administration (FDA) for PET imaging in men with recurrent prostate cancer. The clinical trial program to support the safety and efficacy, in terms of diagnostic performance, of 18F-fluciclovine PET imaging in adults for the detection and continuing assessment of glioma encompasses four trials conducted in Japan by Nihon Medi-Physics Co., Ltd and two studies in Europe and the United States by Blue Earth Diagnostics. To date, the safety profile of 18F-fluciclovine PET imaging in patients with glioma appears to be consistent with that summarized in the current Axumin prescribing information. 18F-Fluciclovine has been granted Orphan Drug status by both the FDA and the European Medicines Agency for the diagnosis of glioma. The compound was invented at Emory University in Atlanta, Ga., with much of the fundamental clinical development work carried out by physicians at Emory University’s Department of Radiology and Imaging Sciences.

About Glioma

Glioma, the most commonly occurring type of primary brain tumor, is a serious and life-threatening condition. Cancer of the brain and central nervous system (CNS) is the twelfth most common cause of cancer death worldwide. Glioma accounts for about 25% of all brain tumors, and 80% of all malignant brain tumors. The most aggressive form of glioma, glioblastoma multiforme, is associated with significant morbidity and mortality with relatively low 5-year survival estimates after diagnosis. Current treatment options for patients with glioma include surgery, radiation and chemotherapy. Accurate evaluation of the location and extent of a glioma tumor is essential before or during surgery and radiotherapy and in assessing the continuing status of the disease. The detection and assessment of gliomas typically involves magnetic resonance imaging (MRI), which may be complemented by metabolic imaging using an appropriate amino acid-based PET radiopharmaceutical as recommended in the Response Assessment in Neuro-Oncology (RANO) working group and European Association for Neuro-Oncology (EANO) guidelines.1

U.S. Indication and Important Safety Information About Axumin*

INDICATION

Axumin (fluciclovine F 18) injection is indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment.

IMPORTANT SAFETY INFORMATION

Image interpretation errors can occur with Axumin PET imaging. A negative image does not rule out recurrent prostate cancer and a positive image does not confirm its presence. The performance of Axumin seems to be affected by PSA levels. Axumin uptake may occur with other cancers and benign prostatic hypertrophy in primary prostate cancer. Clinical correlation, which may include histopathological evaluation, is recommended.
Hypersensitivity reactions, including anaphylaxis, may occur in patients who receive Axumin. Emergency resuscitation equipment and personnel should be immediately available.
Axumin use contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk of cancer. Safe handling practices should be used to minimize radiation exposure to the patient and health care providers.
Adverse reactions were reported in ≤ 1% of subjects during clinical studies with Axumin. The most common adverse reactions were injection site pain, injection site erythema and dysgeusia.
To report suspected adverse reactions to Axumin, call 1-855-AXUMIN1 (1-855-298-6461) or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Full U.S. Axumin prescribing information is available at www.axumin.com.

*This press release is intended to provide information about Blue Earth Diagnostics’ business in the United States. Please be aware that the approval status and product label for Axumin varies by country worldwide. Refer to the individual country product label for complete information or contact Blue Earth Diagnostics.

On December 10, 2018 Avacta Group plc (AIM: AVCT), the developer of Affimer biotherapeutics and reagents, and LG Chem Life Sciences, the life sciences division of the South Korean LG Group, reported a multi-target collaboration and development agreement (Press release, Avacta, DEC 10, 2018, View Source [SID1234531989]). The agreement provides LG Chem with the exclusive rights to develop and commercialize, on a worldwide basis, multiple Affimer therapeutics intended for treatment of patients in the fields of inflammatory disorders, and oncology. Under the terms of the agreement, Avacta will generate and carry out the discovery, optimization and protein engineering of Affimer drug candidates against a set of undisclosed targets. LG Chem and Avacta will collaborate to progress these candidates through to drug candidate selection and LG Chem will be responsible for preclinical and clinical development and world-wide marketing of any resulting products.

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Additionally, the agreement provides that Avacta and LG Chem will collaborate jointly in the development of two different Affimer PK/ADME modifiers – Affimers that can be fused to other therapeutic proteins to modify certain properties of those biological drug moieties such as serum half-life and tissue localization. Both parties will have the right to develop PK/ADME modified products, and by exercise of an option, to take exclusive responsibility for the development, manufacture and commercialization of those products.

This multi-target therapeutics development agreement provides upfront and near-term milestone payments, plus longer-term clinical development milestones. Avacta will also receive royalties on any future product sales and LG Chem will cover Avacta’s costs of research and development associated with the collaboration. Avacta may receive additional option fees and milestone payments should LG Chem elect to exercise their options for additional targets.

The Affimer technology is Avacta’s proprietary alternative to antibodies with wide applications in the life sciences for drug development, diagnostics and research tools. Avacta’s in-house therapeutic pipeline is focused on immuno-oncology and it expects to advance its lead programme, a PD-L1/LAG3 bispecific, into the clinic in 2020 whilst building out its pipeline of innovative Affimer drug candidates.

Alastair Smith, Chief Executive of Avacta Group, commented:
"I am delighted to be entering into this therapeutic development partnership with LG Chem which is a strong validation of the potential of the Affimer platform.

"This alliance is an exciting opportunity, not only to work with a partner who has first class biologics manufacturing and clinical development capabilities, but who also has a pioneering vision to develop innovative therapies.

"This landmark agreement with LG Chem reflects the substantial progress that we have made in developing the Affimer technology as a therapeutic platform and I look forward to updating the market on future progress and other partnerships."

Dr. Jeewoong Son, President of LG Chem Life Sciences, commented:
"We are very pleased to announce this collaboration with Avacta Group. Utilizing Avacta’s Affimer technology – a novel non-antibody protein format overcoming limitations of classical antibody-based therapy – and LG Chem’s biologics capability in development and manufacturing, it will take us to the next level of treatment paradigm and to open up a new horizon in biologics therapeutic strategies. I believe, this innovative collaboration will deliver value to patients and will transform patients’ lives"

On December 10, 2018 Bristol-Myers Squibb Company (NYSE: BMY) and Vedanta Biosciences reported a clinical trial collaboration to evaluate Bristol-Myers Squibb’s programmed death-1 (PD-1) immune checkpoint inhibitor Opdivo (nivolumab) in combination with Vedanta Biosciences’ VE800, a rationally-defined human bacterial consortium, in patients with advanced or metastatic cancers (Press release, Bristol-Myers Squibb, DEC 10, 2018, View Source [SID1234531988]).

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In a range of preclinical models of cancer, including those sensitive and resistant to checkpoint inhibition, VE800 was shown to induce CD8+ T cells, potentiate the immune system’s attack of tumor cells, and significantly amplify the effects of anti-PD-1 therapy. These models support clinical research to explore whether modulating the microbiome with VE800 has the potential to broaden the efficacy of checkpoint inhibitors.

"Our lead, microbiome-based immuno-oncology candidate, VE800, is based on work conducted in collaboration with our co-founder, Dr. Kenya Honda, showing in preclinical models that certain gut-dwelling bacterial strains potentiate cytotoxic CD8+ T cells and enhance infiltration into tumors," said Bernat Olle, Ph.D., Co-founder and Chief Executive Officer of Vedanta Biosciences. "Through this collaboration our goal is to determine whether VE800 in combination with Opdivo can improve outcomes for patients with advanced or metastatic cancers."

"We are continuing to explore the novel mechanisms of new assets in combination with our oncology portfolio," said Fouad Namouni, M.D., head of development, oncology, Bristol-Myers Squibb. "Vedanta Biosciences is a leading company focused on the characterization of immunomodulatory human gut commensals and the development of live bacterial products for the potential treatment of human diseases. Our collaboration with Vedanta Biosciences will allow us to gain a deeper understanding about the emerging microbiome landscape, its role in oncology, and the potential to improve outcomes for patients with advanced or metastatic cancer."

"Checkpoint inhibitors, particularly PD-1 antibodies, have been a major advance in cancer therapy; however, a large proportion of patients either do not respond or have response of brief duration to those new therapies," said Jeffrey Weber, M.D., Ph.D., Deputy Director, Laura and Isaac Perlmutter Cancer Center and Professor of Medicine, NYU Langone Health. "Alteration of the gut microbiome could play a significant role in enhancing the effectiveness of checkpoint inhibitors, and with increased understanding may also be used to select for patients who would benefit most from these immunotherapies."

In conjunction with this collaboration, and subject to the completion of due diligence, the negotiation by the parties of definitive transaction agreements and the receipt by Bristol-Myers Squibb of all requisite approvals, Bristol-Myers Squibb currently intends to make an equity investment in Vedanta Biosciences. Vedanta Biosciences will maintain control of its VE800 program, including global R&D and commercial rights.

About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

U.S. FDA-APPROVED INDICATIONS FOR OPDIVO
OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with intermediate or poor-risk, previously untreated advanced renal cell carcinoma (RCC).

OPDIVO (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

IMPORTANT SAFETY INFORMATION

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients.

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=12).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients.

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. For patients without HCC, withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4. For patients with HCC, withhold OPDIVO and administer corticosteroids if AST/ALT is within normal limits at baseline and increases to >3 and up to 5 times the upper limit of normal (ULN), if AST/ALT is >1 and up to 3 times ULN at baseline and increases to >5 and up to 10 times the ULN, and if AST/ALT is >3 and up to 5 times ULN at baseline and increases to >8 and up to 10 times the ULN. Permanently discontinue OPDIVO and administer corticosteroids if AST or ALT increases to >10 times the ULN or total bilirubin increases >3 times the ULN. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients.

In Checkmate 040, immune-mediated hepatitis requiring systemic corticosteroids occurred in 5% (8/154) of patients receiving OPDIVO.

Immune-Mediated Endocrinopathies

OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients.

Immune-Mediated Nephritis and Renal Dysfunction

OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients.

Immune-Mediated Skin Adverse Reactions

OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients.

Immune-Mediated Encephalitis

OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids.

Other Immune-Mediated Adverse Reactions

Based on the severity of the adverse reaction, permanently discontinue or withhold OPDIVO, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1.0% of patients receiving OPDIVO: myocarditis, rhabdomyolysis, myositis, uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, GuillainBarré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), motor dysfunction, vasculitis, aplastic anemia, pericarditis, and myasthenic syndrome.

If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, which has been observed in patients receiving OPDIVO and may require treatment with systemic steroids to reduce the risk of permanent vision loss.

Infusion Reactions

OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate study in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO.

Complications of Allogeneic HSCT after OPDIVO

Complications, including fatal events, occurred in patients who received allogeneic HSCT after OPDIVO. Outcomes were evaluated in 17 patients from Checkmate 205 and 039, who underwent allogeneic HSCT after discontinuing OPDIVO (15 with reduced-intensity conditioning, 2 with myeloablative conditioning). Thirty-five percent (6/17) of patients died from complications of allogeneic HSCT after OPDIVO. Five deaths occurred in the setting of severe or refractory GVHD. Grade 3 or higher acute GVHD was reported in 29% (5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of patients. A steroid-requiring febrile syndrome, without an identified infectious cause, was reported in 35% (n=6) of patients. Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic encephalitis without an identified infectious cause, and Grade 3 (n=1) suspected viral encephalitis. Hepatic veno-occlusive disease (VOD) occurred in one patient, who received reduced-intensity conditioned allogeneic HSCT and died of GVHD and multi-organ failure. Other cases of hepatic VOD after reduced-intensity conditioned allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor blocking antibody before transplantation. Cases of fatal hyperacute GVHD have also been reported. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT.

Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly.

Embryo-Fetal Toxicity

Based on its mechanism of action, OPDIVO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO-containing regimen and for at least 5 months after the last dose of OPDIVO.

Lactation

It is not known whether OPDIVO is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 032, serious adverse reactions occurred in 45% of patients receiving OPDIVO (n=245). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, pneumonitis, pleural effusion, and dehydration. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, adverse reactions leading to discontinuation occurred in 7% and dose delays due to adverse reactions occurred in 34% of patients (n=266). Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions reported in ≥1% of patients were pneumonia, infusion-related reaction, pyrexia, colitis or diarrhea, pleural effusion, pneumonitis, and rash. Eleven patients died from causes other than disease progression: 3 from adverse reactions within 30 days of the last OPDIVO dose, 2 from infection 8 to 9 months after completing OPDIVO, and 6 from complications of allogeneic HSCT. In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=236). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. In Checkmate 040, serious adverse reactions occurred in 49% of patients (n=154). The most frequent serious adverse reactions reported in ≥2% of patients were pyrexia, ascites, back pain, general physical health deterioration, abdominal pain, and pneumonia. In Checkmate 238, Grade 3 or 4 adverse reactions occurred in 25% of OPDIVO-treated patients (n=452). The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of OPDIVO-treated patients were diarrhea and increased lipase and amylase. Serious adverse reactions occurred in 18% of OPDIVO-treated patients.

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 032, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=245) were fatigue (45%), decreased appetite (27%), musculoskeletal pain (25%), dyspnea (22%), nausea (22%), diarrhea (21%), constipation (20%), and cough (20%). In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were fatigue (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=266) were upper respiratory tract infection (44%), fatigue (39%), cough (36%), diarrhea (33%), pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%), and pruritus (20%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO (n=236) were cough and dyspnea at a higher incidence than investigator’s choice. In Checkmate 275, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%). In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO as a single agent, the most common adverse reactions (≥20%) were fatigue (54%), diarrhea (43%), abdominal pain (34%), nausea (34%), vomiting (28%), musculoskeletal pain (28%), cough (26%), pyrexia (24%), rash (23%), constipation (20%), and upper respiratory tract infection (20%). In Checkmate 040, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=154) were fatigue (38%), musculoskeletal pain (36%), abdominal pain (34%), pruritus (27%), diarrhea (27%), rash (26%), cough (23%), and decreased appetite (22%). In Checkmate 238, the most common adverse reactions (≥20%) reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs 15%), and abdominal pain (21% vs 23%). The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%).

Please see U.S. Full Prescribing Information for OPDIVO.

About VE800

VE800 is Vedanta Biosciences’ oral immuno-oncology product candidate. It consists of a rationally-defined bacterial consortium that activates cytotoxic CD8+ T cells, a type of white blood cell that is the predominant effector in cancer immunotherapy. In preclinical studies, VE800 has been shown to enhance the ability of these T cells to infiltrate tumors, thereby promoting suppression of tumor growth and enhancing survival. Data also suggest that VE800 may enhance the effects of checkpoint inhibitors. Vedanta Biosciences is evaluating VE800 alone and in combination with checkpoint inhibitors as a potential treatment for patients with advanced or metastatic cancers.

On December 10, 2018 Merck KGaA, Darmstadt, Germany, a leading science and technology company, which operates its healthcare business in the U.S. and Canada as EMD Serono, reported that the US Food and Drug Administration (FDA) has granted orphan drug designation (ODD) to M7824, the first regulatory designation for the bifunctional immunotherapy, for the treatment of biliary tract cancer (BTC) (Press release, Merck KGaA, DEC 10, 2018, View Source [SID1234531987]). The FDA orphan drug designation follows the recent presentation of the first clinical data for M7824 in BTC at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) congress in October. M7824 is an investigational bifunctional immunotherapy designed to combine co-localized blocking of the transforming growth factor-β and anti-PD-L1 immune escape mechanisms.

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BTC is a collective term for a group of rare and aggressive gastrointestinal cancers, including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder carcinoma (GBC).[1] Approximately 16,000 cases of BTC are estimated to occur every year in the US and collectively these cancers present late in the majority of patients. [1],[2] Treatment options are limited and the median survival rate in the advanced setting is less than one year, objective tumor response with commonly used chemotherapy is typically less than 10% with short duration of response. [1],[3],[5]

"Biliary tract cancer is a rare, notoriously hard-to-treat tumor where existing treatment approaches, such as surgery or chemotherapy, are either not viable or simply don’t deliver acceptable patient outcomes," said Luciano Rossetti, Head of Global Research & Development at the Biopharma business of Merck KGaA, Darmstadt, Germany. "As the first regulatory designation for M7824, Merck KGaA, Darmstadt, Germany is excited about the potential of this new class of immunotherapy in a number of challenging cancers and settings."

The first clinical data for M7824 in BTC, presented at the ESMO (Free ESMO Whitepaper) congress in October, demonstrated clinical activity in Asian patients who had progressed after platinum-based first-line treatment. The ORR among the total of 30 patients was 20%, as assessed by IRC, and responses were observed across PD-L1 levels with a duration of response ranging from 8.3 months to 13.9+ months. Grade 3 or higher TRAEs were experienced by 10 patients (33.3%) and the most common Grade 3 TRAEs were rash (10%) and lipase increase (10%).

FDA Orphan Drug Designation (ODD) is granted to medicines intended to treat rare diseases or disorders that affect fewer than 200,000 people in the US, or those that affect more than 200,000 people but are unlikely to recover the costs of developing and marketing the drug. Medicines that meet the FDA’s ODD criteria qualify for a number of incentives to help support advancement.

M7824 is an investigational bifunctional immunotherapy that combines a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein. Designed to combine co-localized blocking of the two immunosuppressive pathways, M7824 is thought to control tumor growth by potentially restoring and enhancing anti-tumor responses. M7824 is an important part of a novel combination approach that seeks to harness the power of the immune system and address the tremendously complex nature of difficult-to-treat tumors. To-date, more than 670 patients with various types of solid tumors have been treated across the program with M7824. In addition to BTC, M7824 is being studied in solid tumor indications, including non-small cell lung, HPV associated tumors and gastrointestinal cancers, such as gastric cancer, esophageal squamous cell carcinoma and esophageal adenocarcinoma.

About M7824

M7824 is an investigational bifunctional immunotherapy that is designed to combine a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein. M7824 is designed to combine co-localized blocking of the two immunosuppressive pathways – targeting both pathways aims to control tumor growth by potentially restoring and enhancing anti-tumor responses. M7824 is currently in Phase I studies for solid tumors, as well as a trial to investigate M7824 compared with pembrolizumab as a first-line treatment in patients with PD-L1 expressing advanced NSCLC. The multicenter, randomized, open-label, controlled study is evaluating the safety and efficacy of M7824 versus pembrolizumab as a monotherapy treatment.

About the FDA Orphan Designation

FDA orphan drug designation is granted to drugs intended to treat rare diseases or disorders that affect fewer than 200,000 people in the US, or those that affect more than 200,000 people, but are unlikely to recover the costs of developing and marketing the drug. Orphan drug designation by the FDA qualifies the sponsor for incentives provided for in the Orphan Drug Act, which can include protocol assistance for clinical trials, prescription drug user fee waivers, tax incentives and seven years of market exclusivity. The granting of an orphan drug designation does not alter the standard regulatory requirement to establish the safety and effectiveness of a drug through adequate and well-controlled studies to support approval. The orphan drug designation for M7824 applies only to BTC.

About Biliary Tract Cancer (BTC)

BTC is a collective term for a group of rare and aggressive gastrointestinal cancers, including intrahepatic cholangiocarcinoma (iCC), extrahepatic cholangiocarcinoma (eCC), and gallbladder carcinoma (GBC).[1] Surgery is the only curative treatment, but most patients present with advanced disease and therefore have a limited survival.[1] Approximately 140,000 cases of BTC are estimated to occur annually world-wide.[2] However, incidence of BTC varies in different parts of the world: the incidence of cholangiocarcinomas is rising in the Western world, with reports of up to 2 in 100,000[4]. By contrast, in Asian countries, the incidence is much higher.[4] GBC also has an incidence of 2 in 100,000, but is much more prevalent in parts of South America.[4]
Collectively these cancers present late in the majority of patients and long-term outcomes for resectable patients are poor with median survival in the advanced setting less than 1 year.[1],[3]

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