100 项与 University of Colorado Cancer Center 相关的临床结果
0 项与 University of Colorado Cancer Center 相关的专利（医药）
项与 University of Colorado Cancer Center 相关的文献（医药）
2019-10-01·Clinical Cancer Research
Comprehensive genomic landscapes in early and later onset colorectal cancer
作者: Lieu, Christopher H. ; Golemis, Erica A. ; Serebriiskii, Ilya G. ; Newberg, Justin ; Hemmerich, Amanda ; Connelly, Caitlin ; Messersmith, Wells A. ; Eng, Cathy ; Eckhardt, S. Gail ; Frampton, Garrett ; Cooke, Matthew ; Meyer, Joshua E.
Purpose: The incidence rates of colorectal cancers are increasing in young adults. The objective of this study was to investigate genomic differences between tumor samples collected from younger and older patients with colorectal cancer. Exptl. Design: DNA was extracted from 18,218 clin. specimens, followed by hybridization capture of 3,769 exons from 403 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer. Genomic alterations (GA) were determined, and association with patient age and microsatellite stable/microsatellite instability high (MSS/MSI-H) status established. Results: Overall genomic alteration rates in the younger (<40) and older (≥50) cohorts were similar in the majority of the genes analyzed. Gene alteration rates in the microsatellite stable (MSS) younger and older cohorts were largely similar, with several notable differences. In particular, TP53 (FDR < 0.01) and CTNNB1 (FDR = 0.01) alterations were more common in younger patients with colorectal cancer, and APC (FDR < 0.01), KRAS (FDR < 0.01), BRAF (FDR < 0.01), and FAM123B (FDR < 0.01) were more commonly altered in older patients with colorectal cancer. In the MSI-H cohort, the majority of genes showed similar rate of alterations in all age groups, but with significant differences seen in APC (FDR < 0.01), BRAF (FDR < 0.01), and KRAS (FDR < 0.01). Conclusions: Tumors from younger and older patients with colorectal cancer demonstrated similar overall rates of genomic alteration. However, differences were noted in several genes relevant to biol. and response to therapy. Further study will need to be conducted to determine whether the differences in gene alteration rates can be leveraged to provide personalized therapies for young patients with early-onset sporadic colorectal cancer.
Comparing and contrasting predictive biomarkers for immunotherapy and targeted therapy of NSCLC
1区 · 医学
作者: Camidge, D. Ross ; Doebele, Robert C. ; Kerr, Keith M.
The era of personalized medicine for advanced-stage non-small-cell lung cancer (NSCLC) began when biomarker-based evidence of molecular pathway and/or oncogene addiction of the tumour became mandatory for the allocation of specific targeted therapies. More recently, the immunotherapy revolution, specifically, the development of immune-checkpoint inhibitors (ICIs), has dramatically altered the NSCLC treatment landscape. Herein, we compare and contrast the clinical development of immunotherapy and oncogene-directed therapy for NSCLC, focusing on the role of predictive biomarkers. Immunotherapy biomarkers are fundamentally different from oncogene biomarkers in that they are continuous rather than categorical (binary), spatially and temporally variable and reliant on multiple complex interactions rather than a single, dominant determinant. The performance of predictive biomarkers for ICIs might be improved by combining different markers to reduce the assumptive risks associated with each one. Novel combinations with chemotherapy and ICIs complicate biomarker discovery but do not decrease the value of the markers identified. Perfectly predictive biomarkers of benefit from immunotherapy are unlikely to be identified, although exclusionary biomarkers of minimal benefit or an unacceptable risk of toxicity might be feasible. The clinical adoption and applicability of such biomarkers might vary depending on line of treatment, the available therapeutic alternatives and health economic considerations.
2018-10-31·Investigational New Drugs
A phase 1, dose-escalation study of PF-06664178, an anti-Trop-2/Aur0101 antibody-drug conjugate in patients with advanced or metastatic solid tumors
作者: King, Gentry T. ; Eaton, Keith D. ; Beagle, Brandon R. ; Zopf, Christopher J. ; Wong, Gilbert Y. ; Krupka, Heike I. ; Hua, Steven Y. ; Messersmith, Wells A. ; El-Khoueiry, Anthony B.
Purpose and Methods Trop-2 is a glycoprotein over-expressed in many solid tumors but at low levels in normal human tissue, providing a potential therapeutic target. We conducted a phase 1 dose-finding study of PF-06664178, an antibody-drug conjugate that targets Trop-2 for the selective delivery of the cytotoxic payload Aur0101. The primary objective was to determine the maximum tolerated dose and recommended phase 2 dose. Secondary objectives included further characterization of the safety profile, pharmacokinetics and antitumor activity. Eligible patients were enrolled and received multiple escalating doses of PF-06664178 in an open-label and unblinded manner based on a modified continual reassessment method. Results Thirty-one patients with advanced or metastatic solid tumors were treated with escalating doses of PF-06664178 given i.v. every 21 days. Doses explored ranged from 0.15 mg/kg to 4.8 mg/kg. Seven patients experienced at least one dose limiting toxicity (DLT), either neutropenia or rash. Doses of 3.60 mg/kg, 4.2 mg/kg and 4.8 mg/kg were considered intolerable due to DLTs in skin rash, mucosa and neutropenia. Best overall response was stable disease in 11 patients (37.9%). None of the patients had a partial or complete response. Systemic exposure of PF-06664178 increased in a dose-related manner. Serum concentrations of free Aur0101 were substantially lower than those of PF-06664178 and total antibody. No correlation of Trop-2 expression and objective response was observed, although Trop-2 overexpression was not required for study entry. The intermediate dose of 2.4 mg/kg appeared to be the highest tolerated dose, but this was not fully explored as the study was terminated early due to excess toxicity. Conclusion PF-06664178 showed toxicity at high dose levels with modest antitumor activity. Neutropenia, skin rash and mucosal inflammation were dose limiting toxicities. Findings from this study may potentially aid in future antibody drug conjugate design and trials.
LEXINGTON, Mass.--(BUSINESS WIRE)-- Immuno-oncology leader, Agenus Inc. (“Agenus”) (Nasdaq: AGEN), today announced a data update from the phase 1 expansion cohort of botensilimab (multifunctional CTLA-4 antibody) in combination with balstilimab (PD-1 antibody) for patients with advanced, refractory sarcomas has been selected for an oral presentation at the upcoming ESMO Congress, to be held October 20 – 24, 2023 in Madrid, Spain.
Abstract Title: Efficacy and safety of botensilimab (BOT) plus balstilimab (BAL) in patients (pts) with refractory metastatic sarcoma (NCT03860272)
Abstract Number: 1919MO
Presenting Author: Breelyn A. Wilky, MD, Director of Sarcoma Medical Oncology, Deputy Associate Director for Clinical Research, University of Colorado Cancer Center
Presentation Date and Time: 10/21/2023, 10:15pm – 11:45pm CEST
Data presented at the conference will be available to view in the publications section of the Agenus website ( ) following the ESMO Conference.
Botensilimab, an investigational multifunctional CTLA-4 antibody, is designed to extend immunotherapy benefits to "cold" tumors, which have not historically responded to standard of care or other investigational therapies. Besides binding to the CTLA-4 receptor, its Fc-enhanced structure induces a memory immune response, downregulates regulatory T cells, and activates T cells, thereby enhancing immune responses. Approximately 600 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit with the identifiers NCT05608044, NCT05630183, and NCT05529316.
Agenus is a leading immuno-oncology company targeting cancer and infectious diseases with a comprehensive pipeline of immunological agents. The company’s mission is to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants (through SaponiQx). Agenus is headquartered in Lexington, MA. For more information, visit or follow us on LinkedIn and Twitter @agenus_bio.
Forward Looking Statements
This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements relating to the use of botensilimab and balstilimab, for instance, statements regarding therapeutic benefit and efficacy, mechanism of action (including validation of mechanism of action), potency, durability, and safety profile (including the absence of specific toxicities) of the Company’s therapeutic candidates; and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement.
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Bicara Therapeutics, a clinical-stage biotechnology company developing dual-action biologics to elicit a potent and durable immune response, today announced the appointment of David Raben, M.D., as chief medical officer. Dr. Raben joins Bicara with more than 25 years of biopharma and academic translational oncology experience, having most recently served as vice president of global product development and product general manager, oncology, at Amgen.
“David brings extensive oncology drug development experience to Bicara, including in the area of head and neck cancer, and we are thrilled to welcome him to our team,” said Claire Mazumdar, Ph.D., MBA, chief executive officer of Bicara Therapeutics. “This is an exciting time for Bicara following our recent ASCO presentation of positive interim data from our Phase 1/1b study of BCA101 in HPV-negative, recurrent/metastatic head and neck squamous cell carcinoma, and we believe David’s expertise will help propel Bicara as we continue to execute in the clinic and enter our next phase of growth.”
“Bicara’s dual-action approach to treat solid tumors and compelling clinical data presents a unique opportunity to be part of an exciting company that has the potential to make a significant impact for people living with cancer,” said Dr. Raben. “I look forward to helping advance Bicara’s first-in-class bifunctional EGFR/TGF-β Inhibitor, BCA101, in clinical development for head and neck cancer and other solid tumors, as well as the company’s additional pipeline programs.”
Dr. Raben is a board-certified radiation oncologist. In his most recent role as vice president in oncology development at Amgen, his work centered on driving the anti-DLL3 program in neuroendocrine cancers. Prior to Amgen, Dr. Raben served as vice president and franchise leader, clinical development oncology, at Genentech, where his work centered around precision medicine and immunotherapy trials in head and neck and thoracic cancer, in both late-stage and locally advanced settings. Dr. Raben has spent more than 20 years as a professor and an associate member of the University of Colorado Cancer Center, where his main areas of focus have been evaluating and combining novel biologic therapies in the laboratory and in clinical trials for patients with locally advanced cancers of the head and neck and lung.
About Bicara Therapeutics
Bicara Therapeutics is a clinical-stage biotechnology company developing first-in-class biologics engineered to combine the precision of well validated, tumor-targeting antibodies with the power of tumor microenvironment modulators. The company’s bifunctional antibodies are designed to deliver an immunomodulatory payload directly to the tumor microenvironment to ramp up immune cell activity, offering the potential for synergistic therapeutic impact at the site of the tumor. Bicara’s lead product candidate, BCA101, is a first-in-class EGFR/TGF-β-trap bifunctional antibody currently being evaluated in a Phase 1/1b study. For more information, please visit or follow us on LinkedIn or Twitter.
New research shows that a microfluidic squeezing technology helps stimulate anti-tumor activity in a subtype of HPV16-positive cancers.
Over the past decade, human papillomavirus (HPV) has increasingly been identified as a significant cause of certain head and neck cancers -- for example, evidence suggests it causes 70% of oropharyngeal cancers in the United States.
Further, over the past three decades, incidence of HPV-driven cancers has increased substantially worldwide and in the U.S. While there are well-established screening tools, as well as vaccines, for HPV-driven cancers such as cervical cancer, there are fewer resources for HPV-driven head and neck cancers. As a result, researchers are working with a sense of urgency to develop innovative therapeutics to treat them.
One groundbreaking therapeutic has shown significant promise in a phase 1 clinical trial led by Antonio Jimeno, MD, PhD, co-leader of the University of Colorado Cancer Center Developmental Therapeutics Program and the CU Cancer Center head and neck cancer SPORE grant. Research results published today show that a microfluidic squeezing technology used on peripheral blood mononuclear cells (PBMCs), a type of immune cell, helps stimulate anti-tumor activity in a subtype of HPV16-positive cancers, including head and neck, cervical, and anal cancers.
"This technology is quite novel," Jimeno explains. "As opposed to other cell therapies that require a patient's cells to be genetically modified, this involves a different way of manipulating cells that does not lead to genetic modifications. It makes the process faster and perhaps more agile as to what you can direct the cells against."
"Sending them to boot camp"
This research was motivated, in part, by an awareness that people diagnosed with certain HPV-driven head and neck cancers don't have a lot of conventional treatment options. "We're very aware of this situation, so we have a large group of investigators conducting immunotherapy and cell therapy clinical trials so that hopefully soon we will be able to offer patients more effective and less toxic options," Jimeno says.
The phase 1 clinical trial focused on patients with a subtype of HPV16-positive solid tumors. Participants sat for a process called apheresis, which involves removing whole blood and putting it through a centrifuge to separate the whole blood into its individual parts. The aim of the apheresis session is to acquire between 5 to 10 billion PBMCs.
The PBMCs were then sent to a laboratory to be trained to find and kill cancer cells caused by HPV, "basically sending them to boot camp so they learn how to find and attack the cancer," Jimeno says.
Using Cell Squeeze technology, the PBMCs were sent through very tight channels that opened pores on their surface. Then, the cells were fed a peptide, or piece of protein, related to the HPV virus -- one that immune cells usually recognize -- so that they could learn to recognize it and build a memory of it. The aim of the process is to help ensure that the next time these cells encounter HPV-driven cancer cells, they attack.
Once the cells had gone through the Cell Squeeze process, they were infused back into patients during a one-hour outpatient therapy session. This process happened every 21 days and did not require patients to receive concurrent immunosuppression or chemotherapy.
Showing promising results
"It's very early in the process with this technology, but the results we observed in this phase 1 trial are promising," Jimeno says. "The fact that the cells are from a patient's own blood means that rejection is not going to be an issue. Also, the fact that they have not been genetically modified on their surfaces makes them less likely to attract unwanted attention from the immune system."
While some study participants experienced mild side effects such as fatigue, rash, or a slight immune reaction, "the toxicity was perceived to be manageable and significantly outweighed by the benefits," Jimeno says. "We did biopsies before and after therapy, and after the therapy we could see these modified cells we had given back to the patient, and they were activated and sort of 'chewing' at cancer cells.
"Most importantly, we had some patients here in Colorado who were on the therapy for almost a year and their disease remained stable. For cancer patients who have run out of other options, being able to be on a therapy without very serious side effects, that doesn't require a hospital stay or supplementary chemotherapy, is a very appealing option."
Following the phase 1 trial, a phase 1B trial is ongoing that combines first-generation cells and immunotherapies. Another study recently opened that works with a second generation of the PBMCs made in an improved way, Jimeno says. Further, inclusion criteria for the study with second-generation PBMCs are much broader.
Because the process does not require genetic modifications, Jimeno says, it is fast and agile, and has potential for other types of cancer.
"The promise of these cell technologies is that many of them are being developed in a way that they can be actually generated at the point of delivery," Jimeno explains. "We can envision a future where these or similar approaches work, and where we have small processors locally -- for example, at the Gates Biomanufacturing Facility here on campus -- so that we're reducing patient wait times. We could potentially offer a therapy that could be turned around very soon after we collect a patient's cells. This is a super exciting field and that's why we're so interested and working hard to drive this."
100 项与 University of Colorado Cancer Center 相关的药物交易