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Expanded interim data from a phase II clinical trial investigating PDS0101-based triple combination therapy in advanced human papillomavirus (HPV)-positive cancers were recently announced. The triple combination of PDS0101—a novel T-cell HPV-specific immunotherapy—with the tumor-targeting IL-12...
Researchers at The University of Texas MD Anderson Cancer Center have discovered a novel immunotherapy combination, targeting checkpoints in both T cells and myeloid suppressor cells, that successfully reprogrammed the tumor immune microenvironment and significantly improved antitumor responses in...
In a single academic hospital network retrospective case-control study reported in JACC: CardioOncology, Lee et al found that patients with vs without preexisting autoimmune disease who received immune checkpoint inhibitor therapy for cancer had significantly increased risk of cardiovascular...
Rimas V. Lukas, MD, a neuro-oncologist at Northwestern Medicine Lou and Jean Malnati Brain Tumor Institute, Chicago, praised the investigators’ willingness to explore relatively new areas of cancer research. “This is an interesting study by a strong group delving further into the nervous...
A microbiome-derived therapeutic vaccine (EO2401) has demonstrated immune responses and anticancer activity in combination with nivolumab and bevacizumab in patients with recurrent glioblastoma, one of the most difficult-to-treat cancers, according to data presented at the 2022 Society for...
As a result of breakthroughs in immune checkpoint inhibitors over the past decade, immunotherapy has joined surgery, radiation therapy, and chemotherapy as one of the pillars of cancer treatment. However, nearly half of patients still do not benefit from immune checkpoint blockade. During the 2022...
Ryan J. Sullivan, MD, Associate Professor of Medicine at Harvard Medical School, and Associate Professor of Hematology/Oncology at Massachusetts General Hospital, Boston, told The ASCO Post that tumor-infiltrating lymphocyte (TIL) cell therapy is likely to become a standard practice in the field....
Cell therapy with tumor-infiltrating lymphocytes (TIL) may address an important unmet need for patients with difficult-to-treat melanoma after disease progression on immune checkpoint inhibitors, according to data presented during the 2022 Society for Immunotherapy of Cancer (SITC) Annual ...
Commenting on the DESTINY-Breast03 presentation at the 2022 San Antonio Breast Cancer Symposium, Neelima Vidula, MD, a medical oncologist at Mass General Cancer Center, said: “The results highlight the important survival differences of T-DXd [fam-trastuzumab deruxtecan-nxki] compared to T-DM1...
The antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (T-DXd) proved to be superior to the antibody-drug conjugate ado-trastuzumab emtansine (T-DM1), significantly improving progression-free survival and overall survival, in women with unresectable or metastatic HER2-positive breast cancer as ...
In the phase II ARC-7 study, when domvanalimab, a novel antibody that blocks T-cell immunoglobulin and ITIM domain (TIGIT), was added to immunotherapy for patients with stage IV non–small cell lung cancer (NSCLC), the combination resulted in improved response rates and progression-free survival...
In a study reported in JACC: CardioOncology, Kondapalli et al found that cardiovascular events common in the general population were observed both prior to and after initiation of immune checkpoint inhibitor therapy for cancer; myocarditis was more common posttreatment, but infrequent. Agreement...
As reported in the Journal of Clinical Oncology by Thomas Yau, MD, and colleagues, findings in a cohort of the phase I/II CheckMate 040 trial indicated the activity of nivolumab/cabozantinib with or without ipilimumab in patients with advanced hepatocellular carcinoma. Study Details In the...
A team of advanced practice providers in the Department of Hematology/Oncology at Fox Chase Cancer Center have received the 2021 Article of the Year Award from the Journal of the Advanced Practitioner in Oncology (JADPRO). This award is given to one article each year that demonstrates an...
Even as they’ve revolutionized cancer treatment, immune checkpoint inhibitors have been shown to produce a range of adverse immune-related side effects. Researchers have now identified inherited genetic variations that may place patients at high risk for complications when undergoing treatment with ...
The final results of the phase III CheckMate 651 trial showed no significant overall survival benefit with first-line nivolumab/ipilimumab vs the EXTREME regimen (cetuximab plus cisplatin or carboplatin plus fluorouracil for up to six cycles, followed by cetuximab maintenance) in recurrent or...
In a Dutch-Danish phase III trial reported in The New England Journal of Medicine, Rohaan et al found that tumor-infiltrating lymphocyte (TIL) therapy prolonged progression-free survival vs ipilimumab in patients with advanced melanoma. Study Details The open-label trial included 168 patients...
The bispecific T-cell engager molecule blinatumomab was found to improve overall survival for patients with no measurable residual disease (MRD) after initial treatment for B-lineage acute lymphoblastic leukemia (ALL), according to the phase III ECOG-ACRIN E1910 trial presented by Litzow et al at...
The chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel was deemed safe and showed encouraging signs of efficacy in a small pilot trial involving patients with lymphoma of the brain and/or spinal cord, according to findings presented by Caron A. Jacobson, MD, MMSc, and colleagues ...
Jiye Liu, PhD, of Dana-Farber Cancer Institute, discusses study findings that demonstrate KDM6A regulates CD38 and CD48 expression in multiple myeloma. Dr. Liu’s team validated combination treatment with an FDA-approved EZH2 inhibitor plus daratumumab, which can overcome daratumumab resistance in preclinical multiple myeloma models, providing the rationale for combination clinical trials to improve patient outcome (Abstract 148).
Francesco Maura, MD, of the University of Miami, Sylvester Comprehensive Cancer Center, discusses his team’s findings in which they defined a comprehensive catalogue of genomic determinants of response to DKRd (carfilzomib, lenalidomide, dexamethasone) in newly diagnosed multiple myeloma. The researchers have identified a number of new genomic alterations that explain resistance to the agents currently used in combination regimens (Abstract 470).
Eileen M. Boyle, MD, PhD, of the Perlmutter Cancer Center, NYU Langone Health, discusses Fc-mediated antibody effector function, inflammation resolution, and oligoclonality and their role in predicting sustained measurable residual disease negativity in patients with newly diagnosed multiple myeloma who were treated with immunotherapy regimens. For the first time, an analysis of T-cell receptors shows that oligoclonal profiles seen on treatment may influence the fitness of the immune response (Abstract 100).
Researchers from the University of Pennsylvania’s Abramson Cancer Center presented preliminary results of an ongoing phase I clinical trial demonstrating successful retreatment with chimeric antigen receptor (CAR) T-cell therapy for patients whose cancers relapsed after previous CAR T-cell therapy. ...
Joseph Schroers-Martin, MD, of Stanford University, discusses immunogenomic features reflecting divergent biology in posttransplant lymphoproliferative disorders (PTLD). These include evidence of mismatch repair defects in Epstein-Barr virus–positive PTLD, tumor microenvironment depletion, and MYC pathway enrichment in certain patients (Abstract 72).
Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, discusses the outcomes of patients newly diagnosed with acute myeloid leukemia (AML) who were treated with cytarabine plus daunorubicin plus gemtuzumab ozogamicin (GO). These patients experienced higher rates of measurable residual disease–negative complete remission and complete remission with incomplete count recovery, compared to those treated with cytarabine plus idarubicin daunorubicin alone. Although adding GO was not associated with improved overall survival, longer follow-up is warranted to determine an absolute survival advantage of this regimen (Abstract 58).
The latest analysis of the TROPiCS-02 breast cancer trial shows that sacituzumab govitecan-hziy is effective in patients with a wide range of Trop-2 expression levels. The findings were reported at the 2022 San Antonio Breast Cancer Symposium by Hope S. Rugo, MD, FASCO, Professor of Medicine and...
In an early-phase trial, nearly three-quarters of patients who received talquetamab—a first-in-class, off-the-shelf, T-cell–redirecting bispecific antibody targeting both the GPRC5D and CD3 receptors—for relapsed or refractory multiple myeloma saw a significant reduction in cancer burden within a...
Tycel J. Phillips, MD, of the City of Hope National Medical Center, discusses data that showed fixed-duration glofitamab monotherapy induced high and durable complete response rates in patients with mantle cell lymphoma (MCL) who received obinutuzumab pretreatment. This is one of the largest data sets and longest follow-ups reported with a CD20/CD3 bispecific monoclonal antibody for patients with relapsed or refractory MCL (Abstract 74).
On December 9, the U.S. Food and Drug Administration (FDA) approved atezolizumab (Tecentriq) for the treatment of adult and pediatric patients aged 2 years and older with unresectable or metastatic alveolar soft-part sarcoma (ASPS). Study ML39345 Efficacy was evaluated in Study ML39345...
On November 8, 2022, cemiplimab-rwlc was approved for use in combination with platinum-based chemotherapy for first-line treatment of patients with advanced non–small cell lung cancer (NSCLC) with no EGFR, ALK, or ROS1 aberrations.1 Supporting Efficacy Data Approval was supported by findings in the ...
On September 2, 2022, durvalumab was approved for use in combination with gemcitabine/cisplatin for the treatment of patients with locally advanced or metastatic biliary tract cancer.1 Supporting Efficacy Data Approval was based on findings in the double-blind TOPAZ-1 trial (NCT03875235), in which...
Sara A. Hurvitz, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, discusses phase II results from the TRIO-US B-12 TALENT study, which showed that patients with localized, hormone receptor–positive, HER2-low breast cancer who are treated with fam-trastuzumab deruxtecan-nxki (T-DXd) in the neoadjuvant setting had an overall response rate (ORR) of 68%. When combined with anastrozole, T-DXd led to a 58% ORR. This is the first trial to evaluate T-DXd in HER2-low breast cancer, a potentially curable disease (Abstract GS2-03).
Sara A. Hurvitz, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, discusses phase III findings from the DESTINY-Breast03 study, which showed that second-line treatment with fam-trastuzumab deruxtecan-nxki (T-DXd) led to longer overall survival compared with ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer. Patients treated with T-DXd had a 36% lower risk of death than those treated with T-DM1 (Abstract GS2-02).
As reported in The Lancet Oncology by Paolo A. Ascierto, MD, and colleagues, the second interim overall survival analysis of the phase III IMspire150 trial has shown a numeric but statistically nonsignificant improvement with the addition of first-line atezolizumab to vemurafenib and cobimetinib in ...
As reported in the Journal of Clinical Oncology by Sonneveld et al, the final overall survival analysis of the phase III CASTOR trial has shown a significant overall survival benefit with daratumumab plus bortezomib/dexamethasone (D-Vd) vs bortezomib/dexamethasone alone (Vd) in patients with...
Compared with capecitabine-based regimens, fam-trastuzumab deruxtecan-nxki (T-DXd) led to higher response rates and longer survival in the third-line setting for patients with HER2-positive metastatic breast cancer previously treated with ado-trastuzumab emtansine (T-DM1), according to results from ...
Patients with localized, hormone receptor (HR)-positive, HER2-low breast cancer treated with fam-trastuzumab deruxtecan-nxki (T-DXd) in the neoadjuvant setting had an overall response rate of 75% without combining the agent with anastrozole and 63% in combination with anastrozole, according to...
In a retrospective study reported in JAMA Oncology, Rakaee et al found that tumor-infiltrating lymphocyte (TIL) levels ascertained via machine learning–based scoring on standard histologic images were associated with response in patients receiving immune checkpoint inhibitor therapy for non–small...
Sumanta Pal, MD, of the City of Hope Comprehensive Cancer Center, discusses phase I results from the COBALT-RCC study, a first-in-human clinical trial exploring CD70 CAR T-cell therapy in patients with clear cell renal cell carcinoma. The agent appeared to show an excellent safety profile with no unexpected toxicities and antitumor activity. One durable complete response is the first to be achieved with allogeneic CAR T-cell therapy in patients with relapsed or refractory solid tumors, offering proof of concept for further exploration of CD70-targeted CAR T cells in renal cell and other CD70-positive malignancies (Abstract 558).
Taken together with the primary clinical results, a secondary analysis of the phase III SWOG S1404 randomized clinical trial demonstrated that pembrolizumab provides superior clinical and patient-reported quality-of-life outcomes compared to standard of care with adjuvant ipilimumab or high-dose...
In the phase Ib/II JAVELIN PARP Medley trial reported in JAMA Oncology, Timothy A. Yap, MBBS, PhD, and colleagues found that the combination of the anti–PD-L1 agent avelumab and the poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib produced objective response rates in patient subgroups with ...
As reported in the Journal of Clinical Oncology by Laetsch et al, the 3-year update of the phase II ELIANA trial showed durable responses and a manageable safety profile with tisagenlecleucel for the treatment of pediatric and young adult patients with relapsed or refractory B-cell acute...
Roger Li, MD, of the H. Lee Moffitt Cancer Center, discusses results from a phase II single-arm study of CG0070, a cancer-selective oncolytic adenovirus that creates mechanistic synergy with immune checkpoint blockade. In this trial, the virus was combined with pembrolizumab in patients with non–muscle-invasive bladder cancer that is unresponsive to bacillus Calmette-Guérin. At 3 months, 88% of the 35 patients enrolled achieved a complete response (Abstract 666).
Michael B. Atkins, MD, of Georgetown Lombardi Comprehensive Cancer Center, explores recent clinical trials in immuno-oncology in which the phase III trial produced markedly different results from the phase II trial. To help understand the potential value to patients of late-stage trials of treatment combinations, the Society for Immunotherapy of Cancer has developed a checklist for investigators, applicable to any regimen in which immune modulation is an important component of the antitumor effect.
Kishu Ranjan, PhD, of Yale University School of Medicine, discusses his study findings, which identified a deficiency in the biomarker TAP2 as a prominent immune evasion mechanism in patients whose non–small cell lung cancer has resisted immunotherapy (Abstract 148).
As reported in the Journal of Clinical Oncology by Yamaguchi et al, an exploratory cohort analysis in a Japanese/South Korean phase II trial (DESTINY-Gastric01) indicated that fam-trastuzumab deruxtecan-nxki (TDX-d) showed activity in previously treated—but anti-HER2 treatment–naive—patients with...
Jonathan Chen, MD, PhD, of Massachusetts General Hospital, discusses “immunity hubs” that interact with a reservoir of stem-like CD8 T cells and appear to be associated with subsequent response to anti–PD-1 blockade in patients with non–small cell lung cancer. Hybrid hubs, Dr. Chen says, are a favorable class of immunity hub notable for CD8-positive and TCF7-positive cells, as well as CCL19 expression (Abstract 956).
Saman Maleki, PhD, of Canada’s Western University and Lawson Health Research Institute, discusses modifying the gut microbiome in patients with advanced melanoma to induce a response to anti–PD-1 therapy and potentially reduce primary resistance to immunotherapy. A fecal microbiota transplant from healthy donors before treatment appears to be beneficial (Abstract 614).
Julia Tchou, MD, PhD, of the University of Pennsylvania, discusses preliminary results of the phase Ib/II BreastVax study, which suggested a single preoperative pembrolizumab dose plus a tumor-targeting radiation boost may result in pathologic response in patients with early-stage triple-negative breast cancer (Abstract 644).
In a registry-based retrospective cohort study reported in JAMA Oncology, Ziad Bakouny, MD, and colleagues in the COVID-19 and Cancer Consortium (CCC19 registry) found that patients receiving cancer immunotherapy who had baseline immunosuppression, but not those without baseline immunosuppression,...