Paul G. Richardson, MD, clinical program leader and director of Clinical Research for the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, and RJ Corman Professor of Medicine at Harvard Medical School, discusses the response rates observed in the first-in-human phase 1 trial (NCT03374085) of CC-92480 and dexamethasone in patients with relapsed/refractory multiple myeloma.

Richardson said the overall response rate (ORR) for all of the evaluable patients in the study was about 21%, and the ORR for the patients treated at the maximum tolerated dose was encouraging at 40%, including 2 patients with complete response. When Richardson and the investigators looked at the best schedule, the response rate was at about 55% for the recommended phase 2 dose.

The majority of patients, about 70%, who were receiving the combination at 1 mg for 3 weeks and then were off for 1 week, were triple-class refractory and achieved complete responses and very good partial responses, which was exciting, according to Richardson.

For patients who had extramedullary disease and were receiving 1 mg, there were observed responses reflected by paraproteins and the disappearance of extramedullary disease on scans, which was something the investigators did not expect, Richardson says. All of the responses were durable in the study.

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Videos

Paul G. Richardson, MD, discusses the response rates observed in the first-in-human phase 1 trial of CC-92480 and dexamethasone in patients with relapsed/refractory multiple myeloma.

Evaluating Response Rates With CC-92480 Combination in Multiple Myeloma

Treatment Options in HER2+ Metastatic Breast Cancer

Trastuzumab Emtansine in HER2+ Breast Cancer

Options in Breast Cancer After HER2+ Targeted Therapy

Trastuzumab Deruxtecan in HER2+ Breast Cancer

Dr Mark Pegram and Dr Julie Gralow discuss treatment options in relapsed/refractory HER2+ metastatic breast cancer. 

Expanding Options for Relapsed/Refractory HER2+ Metastatic Breast Cancer

Caron Jacobson, MD, medical director of the Immune Effector Cell Therapy Program and physician at Dana-Farber Cancer Institute, and assistant professor of medicine at Harvard Medical School, discusses the safety findings from the phase 2 ZUMA-5 tidal evaluating a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, axicabtagene ciloleucel (axi-cel; Yescarta), in patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL).

The safety profile was a little better in the FL cohort, so much so that it potentially raises the question of whether axi-cel could be administered in the outpatient setting, Jacobson says. About 23% of patients in the FL cohort had no cytokine release syndrome (CRS), and among those that did have CRS, the median time to onset was 4 days as opposed to 2 days in large cell lymphoma. Only 7% if patients in the FL cohort had high-grade CRS.

In terms of neurological toxicity in the FL cohort, 15% had high-grade events, which remains in line with what is expected with axi-cel in large cell lymphoma, Jacobson says.

The MZL cohort had a slightly higher incidence of CRS and higher-grade neurological toxicity that was more aligned with data for diffuse large B-cell lymphoma, according to Jacobson. The median time to onset of CRS in this cohort was about 4 days as well, so it was the same degree of toxicity with the FL cohort but later than we are used to seeing in large cell lymphoma.

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Caron Jacobson, MD, discusses the safety findings from the phase 2 ZUMA-5 tidal evaluating axicabtagene ciloleucel in patients with follicular lymphoma and marginal zone lymphoma.

Toxicity Profile of CAR T-Cell Therapy Appears Safe in Follicular and Marginal Zone Lymphomas

Matthew S. Davids, MD, associate director of the Center for Chronic Lymphocytic Leukemia, director, Clinical Research for the Lymphoma Program at the Dana-Farber Cancer Institute, and associate professor of Medicine at Harvard Medical School, discusses the long-term follow-up of a phase 1/1b trial (NCT02268851) for patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) receiving ibrutinib (Imbruvica) and umbralisib.

The initial results were presented early in 2019 with about 2 years of follow-up, showing high rates of response in patients with CLL and MCL, according to Davids. There was good tolerability observed for these patients, and the investigators were able to identify the recommended phase 2 dose for umbralisib of 800 mg combined with the standard dose of ibrutinib.

The challenge with the initial report was that the follow-up for these patients was short, Davids says. The goal of the update at the 2020 European Hematology Association Congress was to present about 4 years of follow-up of the progression-free survival (PFS) and overall survival (OS) of the high-risk patients. The investigators also looked at the rates of complete remission, which increased over time.

For patients with MCL, the median PFS was around 11 months, and the median OS was about 2 and a half years. Davids thinks that this didn’t look much different than ibrutinib monotherapy, and it is hard to tell if there is a difference between monotherapy and this combination.

Davids says the investigators saw the bigger difference in the patients with CLL compared to historical control studies. There was about an 80% 4-year PFS in the high-risk CLL population and a 4-year OS of 90%. There are still many patients on the ibrutinib and umbralisib combination. The data set highlights the efficacy and safety of dual B-cell receptor blockade and warrants further study, he believes.

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Matthew S. Davids, MD, discusses the long-term follow-up of a phase 1/1b trial for patients with relapsed/refractory chronic lymphocytic leukemia or mantle cell lymphoma receiving ibrutinib and umbralisib. 

Long-Term Results of Ibrutinib/Umbralisib Show Efficacy in CLL and MCL

Xiuning Le, MD, PhD, an assistant professor in the Department of Thoracic Head and Neck Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the results of tepotinib (Tepmetko) in patients with advanced non-small cell lung cancer (NSCLC) and a MET exon 14 skipping mutation.

The phase 2 VISION trial (NCT02864992) was massively positive, says Le. In the 99 patients the investigators could report on, there was about 46% objective response rate. To get a real response, she says the tumor has to shrink by at least 30%. In the 99 patients, there was 90% tumor shrinkage.

Le says the hypothesis for the study was correct due to these findings. The small molecule inhibitor tepotinib works on the tumor and induces tumor shrinkage. There were some patients with more tumor shrinkage than others on the trial, but overall the results were positive and showed that tepotinib works for this patient population.

There was a median progression-free survival of 8.6 months with this drug by independent review committee and 9.5 months by investigator assessment.

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Xiuning Le, MD, PhD, discusses the results of tepotinib in patients with advanced non-small cell lung cancer and a MET exon 14 skipping mutation.

VISION Trial Produces Positive Data in NSCLC With MET Exon 14 Mutations

Bradley Monk, MD, a professor on the Clinical Scholar Track at the University of Arizona College of Medicine, Phoenix and a gynecologic oncologist at Arizona Oncology (US Oncology Network), discusses the phase 1b/2 innovaTV 205 (ENGOT-cx8/GOG-3024; NCT03786081) trial in patients with recurrent or metastatic cervical cancer.

This study is looking at the combination of tisotumab vedotin plus bevacizumab (Avastin), pembrolizumab (Keytruda), or carboplatin (Paraplatin). Testing these combinations makes sense biologically and mechanistically, according to Monk. The patients on this trial, who progressed on their second-line of therapy or later, will be in 1 of the 3 dose-escalation arms. The investigators identified the appropriate doses of tisotumab plus each of the 3 other therapies.

Monk explains that in the same space where these agents are used in earlier lines of therapy, the investigators will see how they will affect patients by way of dose expansion. To find the recommended phase 2 dose, patients will receive therapy with 1 of the combinations every 3 weeks. Because the half-life is only 1.7 days, there will be a fourth arm in the phase 2 looking at weekly dosing.

There will be an interim analysis after 15 patients are enrolled in each arm. The primary end point is overall survival. Monk says the investigators are also interested in the adverse events associated with these combinations. One adverse event associated with tisotumab is epistaxis, an eye toxicity, which they have a mitigation strategy for of eye drops. Patients on this drug also can also experience fatigue and neuropathy.

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Bradley Monk, MD, discusses the phase 1b/2 innovaTV 205 trial in patients with recurrent or metastatic cervical cancer.

Investigating Combinations in Recurrent or Metastatic Cervical Cancer

Nancy U. Lin, MD, associate professor of medicine at Harvard Medical School; associate chief of the Division of Breast Oncology at the Susan F. Smith Center for Women's Cancers; and director of the Metastatic Breast Cancer Program at the Dana-Farber Cancer Institute, discusses the latest findings from the HER2CLIMB study (NCT02614794) of either tucatinib (Tukysa) or placebo, added to trastuzumab (Herceptin) and capecitabine (Xeloda), for patients with previously treated HER2-positive metastatic breast cancer who have brain metastases.

The HER2CLIMB trial enrolled about 600 patients, of which 291 patients had brain metastases at baseline, which Lin says is a unique feature of this clinical trial. Of the 291 patients, 60% had new or active brain metastases when entering the study. She and the other investigators were looking at outcomes of patients with brain metastases enrolled on HER2CLIMB.

With the tucatinib regimen, the investigators found the intracranial response rate was higher. About half of patients on the triplet achieved a central nervous system (CNS) partial response or better compared with about 20% who received the placebo regimen. Lin says that more importantly, there was a prolongation of the CNS progression-free survival, which was defined as time from randomization to CNS progression or death. CNS progression was reduced by about two-thirds for patients receiving tucatinib, and there was a 5-month absolute improvement in median time to CNS progression or death.

There was a significant improvement in overall survival for the brain metastasis population receiving the triplet regimen. The hazard ratio for survival was 0.58, and there was an absolute improvement of about 6 months for the median overall survival with tucatinib in this difficult-to-treat patient population, according to Lin.

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Nancy U. Lin, MD, discusses the latest findings from the HER2CLIMB study of either tucatinib or placebo, added to trastuzumab and capecitabine, for patients with previously treated HER2-positive metastatic breast cancer who have brain metastases.

HER2CLIMB Study Shows Efficacy in HER2 Breast Cancer With Brain Metastases

Challenges Associated with GIST Management

Mutations in Gastrointestinal Stromal Tumors

GIST Mutations: Are Some Worse Than Others?

GIST Mutations: Treatment Decision Factors

Key opinion leaders discuss the evolving treatment paradigm for relapsed/refractory gastrointestinal stromal tumors, and provide an overview of supplemental data presented at the ASCO (American Society of Clinical Oncology) 2020 Annual Meeting.

Expanding Options for Relapsed/Refractory Gastrointestinal Stromal Tumors

Shubham Pant, MD, an associate professor in the Department of Investigational Cancer Therapeutics and the Department of Gastrointestinal Medical Oncology at the University of Texas MD Anderson Cancer Center, discusses the ESPAC-5F trial (ISRCTN89500674) methods and efficacy in patients with pancreatic cancer.

This was a prospective, multicenter, randomized phase 2 study with 4 arms for patients with borderline resectable pancreatic cancer. According to Pant, this type of cancer touches some vessels in the patient but does not encase these vessels. The patients either received immediate surgery or neoadjuvant gemcitabine (Gemzar) plus capecitabine (Xeloda) or FOLFIRINOX (folnic acid, fluorouracil, irinotecan, and oxaplatin) or chemoradiotherapy. For the surgery arm, there were 32 patients; 20 were on the gemcitabine and capecitabine regimen, 20 were on the FOLFIRINOX regimen, and 16 patients received chemoradiation.

The investigators found that the 1-year survival rate was 77% for patients receiving neoadjuvant therapy and 40% for those receiving immediate surgery. Pant says this is important because pancreatic cancer is a systemic disease and the micrometastases need to be killed before for patients go in for surgery. Neoadjuvant therapy should be given to most patients who have this disease, and he thinks this should be the standard for most, if not all patients in this setting.

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Shubham Pant, MD, discusses the ESPAC-5F trial methods and efficacy in patients with pancreatic cancer.

Analyzing the ESPAC-5F Trial in Borderline Resectable Pancreatic Cancer

Case 1: GvHD Background

Case 1: A Patient With Acute Graft-Vs-Host Disease

Case 1: Staging of Acute Graft-vs-Host Disease

Case 1: Personal Approach to Treatment for Acute GVHD

Case 2: Steroid-Refractory Acute Graft-Versus-Host Disease

Case 2: Ruxolitinib for Steroid-Refractory Acute GVHD

Case 2: Treating Steroid-Refractory Acute GVHD

Experts in stem cell transplantation review the background of graft-versus-host disease and discuss 3 clinical cases and individualized treatment approaches.