On June 2, 2017 Bristol-Myers Squibb Company (NYSE:BMY) reported the first disclosure of data from a cohort of the Phase 1/2 CheckMate -358 study evaluating Opdivo (nivolumab) for the treatment of patients with advanced cervical, vaginal and vulvar cancers, all associated with infection by the human papillomavirus (HPV) (Press release, Bristol-Myers Squibb, JUN 2, 2017, View Source [SID1234519342]). Schedule your 30 min Free 1stOncology Demo! The cohort included 24 patients, 19 of which were cervical cancer patients. The preliminary efficacy measures from the Phase 1/2 CheckMate -358 study (N=24) in patients with advanced cervical, vaginal and vulvar cancers, included an objective response rate (ORR), the primary endpoint, of 20.8% (95% CI: 7.1 to 42.2), with a 70.8% disease control rate of women experiencing complete or partial response or stable disease. The median progression-free survival (PFS) was 5.5 months (95% CI: 3.5 to not reached) and the median overall survival (OS) was not yet reached. Responses were seen only in cervical cancer patients. Of the 19 women with cervical cancer, five had complete and partial responses, with an ORR of 26.3% (95% CI: 9.1 to 51.2). Median duration of response has not been reached after 6 months of follow-up. Opdivo showed a safety profile consistent with previous results seen with Opdivo monotherapy in other tumor types. Grade 3/4 treatment-related adverse events (AEs) occurred in 12.5% of patients. These data will be presented today in an oral session at 4:12 to 4:24 PM CDT at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2017.
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"These CheckMate -358 results demonstrate the value of studying the potential of an Immuno-Oncology agent to address the significant challenge of treating patients with advanced cervical, vaginal and vulvar cancers," said lead investigator Antoine Hollebecque, M.D., senior medical physician, Gustave Roussy Cancer Institute in Villejuif, France. "As a clinical investigator, I am encouraged by these findings in the women with advanced cervical cancer, and look forward to the anticipated data from the planned longer term analyses."
HPV, which is transmitted through sexual contact, is linked with more than 90% of cervical cancers, about 75% of vaginal cancers and 69% of vulvar cancers. First-line treatment for women with advanced cervical cancer often consists of chemotherapy alone or combined with radiation, and the five-year survival rate for advanced cervical cancer, stages III and IV, ranges from about 35% to 16%.
"This first assessment of Opdivo’s activity in women with advanced cervical, vaginal and vulvar cancers enrolled in this cohort of CheckMate -358 supports further investigation, especially because these patients have very limited options after chemotherapy or radiation fails," said Shinta Cheng, M.D., Ph.D., development lead, Bristol-Myers Squibb. "These trial results also underscore our continued commitment to explore how Immuno-Oncology therapy might benefit as many appropriate patients as possible, including those with virally associated cancers of the gynecological system."
About CheckMate -358 (Abstract #5504)
CheckMate -358 is an ongoing Phase 1/2, open-label, international, multicenter, non-comparative, multi-cohort study that is evaluating the safety and efficacy of Opdivo monotherapy and Opdivo combination therapy in adult patients with virally associated tumors (Merkel cell carcinoma, gastric/gastroesophageal junction carcinoma, nasopharyngeal carcinoma, squamous cell carcinoma of the head and neck, and squamous cell carcinoma of the cervix, vagina, vulva, anal canal and penis).
Patient tumor type, disease stage and resectability determined eligibility for enrollment in one of five treatment cohorts: neoadjuvant Opdivo monotherapy, metastatic Opdivo monotherapy, metastatic Opdivo combination therapy with Yervoy, metastatic Opdivo combination therapy with anti-LAG-3, or metastatic Opdivo combination therapy with daratumumab.
Patients in the neoadjuvant cohort received 2 doses of Opdivo 240 mg intravenously prior to scheduled surgery and patients in the monotherapy cohort were treated with Opdivo 240 mg intravenously every 2 weeks until unacceptable toxicity, withdrawal of consent or disease progression. The primary endpoints of the Phase 2 part of the study are objective response rate by investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria and safety. Secondary endpoints include progression-free survival overall survival, and duration of response.
About HPV & Cervical, Vaginal and Vulvar Cancers
In the majority of patients with human papillomavirus (HPV), which is transmitted through sexual contact, the immune system is effective at eliminating the initial infection. However, 10% to 15% establish life-long persistent infection, which may lead to virally mediated immune suppression and increased risk of cancers like cervical, vaginal and vulvar.
Worldwide, cervical cancer is the fourth most frequent cancer in women with an estimated 530,000 new cases in 2012 and is responsible for 7.5% of all female cancer deaths. Globally, more than an estimated one million women currently live with cervical cancer, as a consequence of a long-term HPV infection. Cancers of the vagina and vulva are rarer than cervical cancer, with estimated new annual diagnoses of 13,000 and 27,000 respectively, which represented 2% and 4% of all gynecological cancers in 2008.
Month: June 2017
CX-1158-101: A first-in-human phase 1 study of CB-1158, a small molecule inhibitor of arginase, as monotherapy and in combination with an anti-PD-1 checkpoint inhibitor in patients with solid tumors
On June 1, 2017 Calithera Biosciences presented the corporate presentation (Presentation, Calithera Biosciences, JUN 1, 2017, View Source [SID1234535274]).
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Lion Biotechnologies Announces First Patient Dosed in Phase 2 Trial of LN-145 for Head and Neck Cancer
On June 1, 2017 Lion Biotechnologies, Inc. (NASDAQ: LBIO), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported that the first patient was dosed in its Phase 2 trial of LN-145 for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (Press release, Lion Biotechnologies, JUN 1, 2017, View Source;p=irol-newsArticle&ID=2278256 [SID1234519425]).
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"We are pleased to have dosed our first patient in this trial evaluating LN-145 for the treatment of head and neck cancer. While some patients benefit from the few options available for the treatment of metastatic squamous cell carcinoma of the head and neck, there remains an unmet medical need for those who progress through such therapies," said Dr. Maria Fardis, PhD, MBA, Chief Executive Officer of Lion Biotechnologies. "With this important milestone, patient dosing is now ongoing in two of our three Lion sponsored Phase 2 programs. We look forward to reporting data from these trials."
LN-145 is an adoptive cell transfer (ACT) therapy that utilizes an autologous TIL manufacturing process as originally developed by the National Cancer Institute. This Phase 2, multicenter, single-arm, open-label interventional study will enroll up to 47 patients and will assess the safety and efficacy of LN-145 for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. The cell transfer therapy used in this study involves patients receiving a non-myeloablative (NMA) lymphocyte depleting preparative regimen, followed by infusion of autologous TIL followed by the administration of a regimen of IL-2.
Additional information on this study is available at www.clinicaltrials.gov.
OBI Pharma Announces Acquisition of TH-3424 from Threshold Pharmaceuticals
On June 1, 2017 OBI Pharma, Inc., a Taiwan biopharma company (TPex: 4174), reported an agreement with Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) to acquire TH-3424, a first-in-class novel small-molecule prodrug that selectively targets cancers overexpressing the enzyme aldo-keto reductase 1c3 (AKR1C3) (Press release, OBI Pharma, JUN 1, 2017, View Source [SID1234525559]). The product will be renamed OBI-3424 effective immediately.
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OBI-3424 is a first-in-class prodrug that selectively releases a potent DNA alkylating agent in the presence of the AKR1C3 enzyme. This selective mode of activation distinguishes OBI-3424 from traditional alkylating agents, such as cyclophosphamide and ifosfamide, which are non-selective.
AKR1C3 overexpression has been documented in a number of treatment-resistant and difficult to treat cancers. For example, hepatocellular carcinomas (HCC), which highly overexpress AKR1C3 in the majority of patients. OBI-3424 has demonstrated potent activities in preclinical models of HCC, including a model resistant to the standard of care treatment, sorafenib. AKR1C3 is adaptively upregulated in response to castration; therefore, castrate-resistant prostate cancer is another logical unmet need population where OBI-3424 will be tested. In addition, the US National Cancer Institute is performing preclinical evaluations of OBI-3424 for the potential treatment of T-cell acute lymphoblastic leukemia (T-ALL).
Furthermore, individualized patient selection by staining for AKR1C3 overexpression by immunohistochemistry can be performed to identify patients with other tumor types most likely to respond to treatment with OBI-3424, thereby offering the possibility for a streamlined clinical development strategy.
Under the terms of the agreement, Threshold will transfer to OBI Pharma its ownership rights as well as preclinical and manufacturing data for OBI-3424 in exchange for an undisclosed, upfront one-time payment. No further payments or future royalties are required. OBI Pharma will obtain Threshold’s global intellectual property as well as the commercial, developmental, and manufacturing rights to OBI-3424, except in certain specified countries in Asia (see footnote 1).
"OBI-3424 is an innovative anticancer drug that can preferentially deliver its payload to cancers that overexpress the activating enzyme, AKR1C3. AKR1C3 is highly overexpressed in a number of cancers that represent unmet medical needs, including hepatocellular carcinoma, castrate-resistant prostate cancer, and T-cell acute lymphoblastic leukemia. OBI-3424 offers the possibility of early efficacy read outs based on objective response rates in well-defined resistant patient populations," said Tillman Pearce, M.D., Threshold’s Chief Medical Officer.
"We will continue the pre-clinical work and hope that OBI-3424 develops into a solid treatment option for patients with cancers that express AKR1C3," said Amy Huang, General Manager of OBI Pharma, Inc. "This novel cancer therapeutic enhances our pipeline and moves us another step towards becoming a global cancer biopharma company. "
OBI Pharma plans to accelerate the development of OBI-3424, with an Investigational New Drug (IND) application filing with the U.S. Food and Drug Administration (FDA) planned for early 2018.
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(1) OBI obtains worldwide rights with the exception of the following countries: China, Hong Kong, Macao, Taiwan, Japan, South Korea, Singapore, Malaysia, Thailand, Turkey and India.
Debiopharm International SA Announces Results from Phase I Dose-Escalation Study of Debio 1347/CH5183284
On June 1, 2017 Debiopharm International SA (Debiopharm – www.debiopharm.com), part of Debiopharm Group, a Swiss-based global biopharmaceutical company, reported the results from the phase I dose-escalation study evaluating the compound Debio 1347/CH5183284 (FGFR 1,2,3 selective inhibitor). The data will be presented at the 53rd American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting by Martin H. Voss, MD, Medical Oncology at the Memorial Sloan Kettering Cancer Center in New York.
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"We are very pleased to have reached this milestone and to be able to see these very interesting and promising results presented at the upcoming ASCO (Free ASCO Whitepaper) meeting. Despite not reaching the MTD, we are confident to have reached the right dose for phase 2 – given the indicators of anti-tumor activity that we have seen", said Chris Freitag, VP Clinical Research & Development.
Oral Abstract Session: Developmental Therapeutics – Clinical Pharmacology and Experimental Therapeutics
TITLE DATE AND TIME N°
Debio 1347, an oral FGFR inhibitor: Results from a first-in-human, phase I dose-escalation study in patients with FGFR genomically activated advanced solid tumors.
Sat, June 3, 1:15 – 1:27
#2500
About Debio 1347/CH5183284
Debio 1347/CH5183284, created by Chugai Pharmaceutical. Co., Ltd., is an orally available small molecule targeting FGFR 1, 2, 3 signaling pathways. Debiopharm International SA completed the dose escalation portion of the first-in-human phase I study. Debio 1347/CH5183284 had a manageable safety profile. Encouraging antitumor activity was seen in several tumor types, mainly in patients with FGFR2 or 3 gene alterations, including fusion events. Efficacy will be further explored in disease-specific and molecularly defined expansion cohort.