Silas Inman

In a phase I/II dose escalation study, there was a complete remission rate of 44% in patients with relapsed/refractory chronic lymphocytic leukemia receiving umbralisib, ublituximab, and venetoclax, according to findings presented at the 2019 ASH Annual Meeting.

Patients with refractory large B-cell lymphoma who were treated with Axi-cel had a 3-year overall survival rate of 47%, according to an updated analysis of the phase II ZUMA-1 trial. 

Encouraging signs of dose-dependent efficacy, as well as a promising safety profile, were observed in patients with heavily pretreated relapsed/refractory multiple myeloma who were treated with CC-93269, a human IgG1-based T-cell engager that binds to BCMA and CD3 epsilon in a 2+1 format.

A multi-antigen off-the-shelf chimeric antigen receptor natural killer cell therapy has been included in the ASH annual meeting spotlight due to exciting preclinical evidence. An investigational new drug application was approved in September 2019 for the therapy, labeled as FT596, developed by Fate Therapeutics, and human trials are scheduled to start in the first quater of 2020.

Immunotherapies and targeted therapies have greatly impacted the treatment of advanced melanoma and are beginning to make their way into earlier settings, with FDA approvals for adjuvant therapies and studies ongoing in the neoadjuvant space, according to a presentation by Jeffrey S. Weber, MD, PhD, at the <em>37th Annual</em> CFS.

A number of promising biologic therapies are beginning to transform the treatment of adult patients with acute lymphoblastic leukemia, with the greatest potential seen with blinatumomab and inotuzumab ozogamicin in combination with chemotherapy, according to a presentation by Hagop M. Kantarjian, MD, at the 37th Annual CFS.<br /> &nbsp;

The wealth of new data available for the treatment of patients with non&ndash;small cell lung cancer has led to numerous effective immunotherapy combinations in similar patient subsets, explained Karen L. Reckamp, MD, MS. Clinical trials going forward seem to primarily focus on the combination of immunotherapeutic and targeted agents, which may result in even more options for this tumor type.

In the phase III INVICTUS trial, ripretinib, a novel KIT and PDGFRA inhibitor, demonstrated a dramatic improvement in progression-free survival compared with placebo in heavily pretreated patients with heavily advanced gastrointestinal stromal tumors, according to data presented at the 2019 ESMO Congress.

Patients with high-grade serous ovarian cancer experienced a 32% reduction in the risk of progression or death with frontline combination veliparib plus carboplatin and paclitaxel followed by veliparib maintenance, according to the data from the phase III VELIA trial presented at the 2019 ESMO Congress, and simultaneously published in the&nbsp;New England Journal of Medicine.

The risk of progression or death was reduced by 63% with&nbsp;ivosidenib as treatment of pretreated patients with IDH1-mutant advanced cholangiocarcinoma&nbsp;compared with placebo, according to data from the phase III&nbsp;ClarIDHy study that was presented at the 2019 ESMO Congress.

In the phase III PROfound trial, olaparib improved radiographic progression-free survival compared to either abiraterone acetate or enzalutamide in men with heavily pretreated metastatic castration-resistant prostate cancer, who had homologous recombination repair gene alterations, according to findings presented at the 2019 ESMO Congress.&nbsp;

Patients with early triple-negative breast cancer receiving neoadjuvant treatment with the combination of pembrolizumab and chemotherapy showed extended pathological complete response rates by 13.6 percentage points compared with chemotherapy alone in the phase III KEYNOTE-522 study.

The combination of olaparib and bevacizumab as frontline maintenance improved the median progression-free survival by 5.5 months over bevacizumab and placebo in patients with&nbsp;newly diagnosed, advanced ovarian cancer following prior treatment with a platinum-based chemotherapy plus bevacizumab, according to the phase III PAOLA-1 findings presented at the 2019 ESMO Congress.

Median overall survival was improved by 6.8 months with osimertinib as a first-line treatment for patients with&nbsp;metastatic, <em>EGFR</em>-mutant non&ndash;small cell lung cancer compared with erlotinib or gefitinib, despite crossover between arms, according to updated data from the phase III FLAURA study presented at the 2019 ESMO Congress.

Median progression-free survival was improved by 5.6 months with PARP inhibitor niraparib as first-line treatment for patients with newly diagnosed, advanced ovarian cancer who responded to platinum-based chemotherapy&nbsp;compared with placebo, according to data from the phase III PRIMA study presented at the ESMO Congress 2019 and simultaneously published in the <em>New England Journal of Medicine</em>.

Studies combining KRAS inhibitor AMG 510 several other is the start of a hopeful era for the treatment of&nbsp;KRAS-mutant non&ndash;small cell lung cancer, according to Vassiliki Papadimitrakopoulou, MD, at the 2019 International Lung Cancer Congress.

EGFR tyrosine kinase inhibitors have remained the frontline standard of care for patients with&nbsp;<em>EGFR-</em>positive non&ndash;small cell lung cancer. The most commonly used EGFR TKI in the frontline setting in the United States is&nbsp;osimertinib, Heather Wakelee, MD, said during a presentation at the 2019 International Lung Cnacer Congress.

Two targeted therapies in development have demonstrated encouraging activity as potential treatments targeting hard-to-target driver alterations in lung cancer. During the 2019 ASCO Annual Meeting,&nbsp;Christine M. Lovly, MD, PhD, reviewed the early promising findings for TAK-788 for patients with&nbsp;non&ndash;small cell lung cancer harboring&nbsp;<em>EGFR</em> exon 20 insertions and for BLU-667 for patients with&nbsp;<em>RET&nbsp;</em>rearrangements.&nbsp;&nbsp;

Promising responses have been seen with 2 highly selective, investigational MET inhibitors&mdash;tepotinib and capmatinib&mdash;in both the&nbsp;first- and second-line setting for patients with&nbsp;<em>MET</em> exon 14&ndash;altered advanced non&ndash;small cell lung cancer.

A subcutaneous formulation of daratumumab showed similar efficacy to the original intravenous formulation of daratumumab in the phase III COLUMBA trial of patients with relapsed/refractory multiple myeloma. The subcutaenous flat-dose of daratumumab also showed a reduction in the treatment burden, according to results presented at the 2019 ASCO Annual Meeting.

Updated data from the phase III EORTC 18071 study showed that patients with&nbsp;surgically resected high-risk, stage III melanoma experienced&nbsp;a 25% reduction in the risk of recurrence or death with adjuvant ipilimumab compared with placebo.

According to findings from the phase III MONALEESA-7 trial, peri and premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer treated with ribociclib plus endocrine therapy demonstrated an estimated overall survival rate of 70.2% at 42 months compared with 46% for placebo and endocrine therapy.

Each of the many BCMA-targeted CAR T cells in development demonstrate a different efficacy and safety profile, and each have different constructs. None of the agents have reached the FDA yet, but data for many of the agents were presented at the 2018 ASH Annual Meeting.

Two-year findings from the ZUMA-1 trial showed an overall survival rate of more than 50% from treatment with&nbsp;axicabtagene ciloleucel, a CD19-targeted CAR T-cell therapy&nbsp;in patients with&nbsp;refractory large B cell lymphoma; the median survival had not yet been reached. These data, representing a clear plateau in the survival curve, were presented at the 2018 ASH Annual Meeting.

Initial results from a phase I study showed an objective response rate of 83.3% had been achieved in&nbsp;heavily pretreated patients with relapsed/refractory multiple myeloma who had been treated with the anti-BCMA CAR T-cell therapy bb21217.

Mosunetuzumab, a&nbsp;CD3 and CD20 bispecific antibody, induced complete remission rates over 30% in patients with&nbsp;relapsed/refractory follicular lymphoma and&nbsp;relapsed/refractory diffuse large B-cell lymphoma or transformed follicular lymphoma, and demonstrated a tolerable safety profile, showing promise for these patients with&nbsp;B-cell indolent and aggressive non-Hodgkin lymphomas.&nbsp;

After 7 years of follow-up, single-agent ibrutinib demonstrated continued efficacy in&nbsp;the frontline and heavily pretreated, relapsed/refractory settings for patients with&nbsp;chronic lymphocytic leukemia and small lymphocytic lymphoma.

After a median of 19 months of follow-up, durable objective response rates were sustained with tisagenlecleucel in patients with relapsed or refractory diffuse large B-cell lymphoma. These updated findings from the phase II JULIET study were presented at the 2018 ASH Annual Meeting.&nbsp;

According to updated data from the phase II ELIANA study,&nbsp;CD19-targeted CAR T-cell therapy tisagenlecleucel as treatment of&nbsp;pediatric and young adult patients with relapsed or refractory acute lymphoblastic leukemia sustained rates of&nbsp;relapse-free survival and overall survival at 24 and 18 months.&nbsp;

Personalized immunotherapy regimens for patients with cancer is a long-term goal of the immuno-oncology field, yet progress toward this goal necessitates the discovery of an effective biomarker for guiding treatment decision making, according to Jason Luke, MD.&nbsp;