Pembrolizumab Reduces Death Rate in Head and Neck Squamous Cell Carcinoma

MedicalResearch.com Interview with:

Ezra Cohen, MD Associate Director, Moores Cancer Center Professor of Medicine Moores Cancer Center UC San Diego Health - La Jolla Moores Cancer Center La Jolla, CA  92093

Dr. Cohen

Ezra Cohen, MD
Associate Director, Moores Cancer Center
Professor of Medicine
Moores Cancer Center
UC San Diego Health – La Jolla
Moores Cancer Center
La Jolla, CA  92093

MedicalResearch.com: What is the background for this study?

Response: We have known for a couple of years that anti-PD1 therapy, and specifically pembrolizumab, is active in  head and neck squamous cell carcinoma (HNSCC). The KN40 trial now tested pembrolizuamb against standard of care in patients whose cancers progressed on platinum containing regimens.

MedicalResearch.com: What are the main findings?

Response: The main findings really supported what we know about pembrolizumab in this disease – it is active and effective with a favorable side effect profile. Pembrolizumab reduced the risk of death by 19% and was associated with a 14% response rate. The effect was even greater in tumors that expressed PDL1 and, in the highest expressing group, the benefit in reduction of risk of death was 46% with a 27% response rate.

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Targeted Immunotherapy Can Prevent Some Melanomas From Spreading

MedicalResearch.com Interview with:

Dr Alexander Menzies BSc(Med) MBBS (Hons) FRACP PhD Medical Oncologist and Senior Research Fellow at Melanoma Institute Australia The University of Sydney and Royal North Shore and Mater Hospital 

Dr. Menzies

Dr Alexander Menzies BSc(Med) MBBS (Hons) FRACP PhD
Medical Oncologist and Senior Research Fellow at Melanoma Institute Australia
The University of Sydney and Royal North Shore and Mater Hospital 

MedicalResearch.com: What is the background for this study?

Response: For early-stage melanoma, surgical resection is the standard treatment and is associated with an excellent long-term prognosis. However until now, Stage III melanoma patients (where the disease has spread to the lymph nodes) who have had their tumours surgically removed have simply had to play the waiting game to see if their melanoma would metastasise, with many ultimately dying of the disease.

Checkpoint inhibitor immunotherapies and drugs that target the mitogen-activated protein kinase (MAPK) pathway have improved the outcome of patients with metastatic melanoma, but their role as adjuvant therapy is still being actively investigated.

Prior Phase III trials (COMBI-D and COMBI-V) have shown improved overall survival in patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations. At Melanoma Institute Australia, we were keen to see if this improvement would be seen in the adjuvant setting also. This clinical trial was the first in the world to give targeted therapy to melanoma patients at an earlier stage of the disease to prevent spread and recurrence.

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Nivolumab Is A Major Advance For Excised Melanoma At Risk of Relapse

MedicalResearch.com Interview with:

Jeffrey Weber, M.D., Ph.D Laura and Isaac Perlmutter Cancer Center New York University Langone Medical Center New York, NY 10016

Dr. Weber

Jeffrey Weber, M.D., Ph.D
Laura and Isaac Perlmutter Cancer Center
New York University Langone Medical Center
New York, NY 10016 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There is a major unmet need for well tolerated and effective adjuvant therapy for high risk melanoma, that is, melanoma that has been removed but the patients have a 50%+ risk of relapse over 5 years, and a 50%+ risk of death over 10 years from melanoma. Since nivolumab is an active and well tolerated drug in metastatic disease, it seemed reasonable to test it after surgery to prevent recurrence. Since ipilimumab is approved for resected stage III melanoma in the US as adjuvant therapy, that was the control arm for comparison, and that is an active control, which prolongs relapse free and overall survival comared to placebo.

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Study Identifies CD70 as a Novel Glioblastoma Target

MedicalResearch.com Interview with:

Jianping Huang, MD, PhD Associate Professor Director of Clinical Laboratory Operations UF Brain Tumor Immunotherapy Program Department of Neurosurgery, University of Florida

Dr. Huang

Jianping Huang, MD, PhD
Associate Professor
Director of Clinical Laboratory Operations
UF Brain Tumor Immunotherapy Program
Department of Neurosurgery, University of Florida

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Identification and validation of molecules that are involved in tumor progression and reduced survival in glioma patients is the starting point for developing active, safe and effective therapy. Unfortunately, very few target molecules have been identified for the deadly disease of glioma up until recently. Our studies have identified that the molecule CD70 is ectopically expressed on gliomas and involved in promoting glioma progression. Our research shows that CD70 leads to a “double jeopardy” scenario in Glioblastoma (GBM) patients by promoting tumor aggressiveness and inhibiting our immune response to cancer. These results provide a strong scientific rationale to target CD70 using state-of-the-art therapeutic approaches, such as chimeric antigen receptor (CAR) T cell therapy.

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Study Reports Hair Repigmentation During Immunotherapy For Lung Cancer

MedicalResearch.com Interview with:
Dr. Noelia Rivera MD

Dermatologist
Hospital Universitari Germans Trias i Pujol, Badalona
Universitat Autònoma de Barcelona

MedicalResearch.com: What is the background for this study?

Response: In the last few years some new therapies targeting immune checkpoints have been developed. The programmed death receptor-1 (PD-1) are immune checkpoints that prevent the immune system to act against own tissues. By blocking these mediators it is possible to prevent tumors to escape from the immune system.

About half of the patients receiving these therapies will develop mild to moderate cutaneous adverse events. In the pre-authorization studies for malignant melanoma these include rash, vitiligo, and pruritus. “Rash” has commonly been reported as an adverse event in many oncologic trials evaluating the drugs, without providing further information about the clinical or histological details. Lately, lichenoid eruptions associated to these therapies have been reported and it suggests that an important percentage of these reactions present lichenoid histological features.

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Combination Therapy With DARZALEX® (daratumumab) Provides Clinical Benefit In Relapsed Myeloma

MedicalResearch.com Interview with:

Dr. Ajai Chari, MD Associate Professor of Medicine Multiple Myeloma Program and Associate Director of Clinical Research Mount Sinai Hospital, New York

Dr. Ajai Chari

Dr. Ajai Chari, MD
Associate Professor of Medicine
Multiple Myeloma Program and
Associate Director of Clinical Research
Mount Sinai Hospital, New York

MedicalResearch.com: What is the background for this study? Would you briefly explain multiple myeloma (How common is it, whom does it chiefly affect, etc.)?

Response: Multiple myeloma is a rare form of blood cancer that occurs when plasma cells grow uncontrollably in the bone marrow. It is estimated that approximately 30,280 people will be diagnosed and 12,590 will die from the disease in the United States in 2017. While some patients with multiple myeloma have no symptoms at all, symptoms can include bone fracture or pain, low red blood counts, fatigue, calcium elevation, kidney problems or infections. Despite tremendous progress, most patients with multiple myeloma continually relapse or become resistant to available therapies, such as proteasome inhibitors (PIs) and immunomodulatory agents. Therefore, these patients continue to need new options.

The MMY1001 (EQUULEUS) study is a Phase 1b, open-label study assessing daratumumab in combination with multiple backbone regimens for multiple myeloma. In one arm of the study, supporting the recent approval of DARZALEX (daratumumab), the treatment was assessed in combination with pomalidomide and dexamethasone in patients with multiple myeloma who had received a prior PI and an immunomodulatory agent. Data from the study showed that the addition of daratumumab resulted in an overall response rate (ORR) of 59.2 percent (95 percent CI: 49.1 percent, 68.8 percent), with very good partial response (VGPR) achieved in 28.2 percent of patients. Complete response (CR) was achieved in 5.8 percent of patients and stringent CR (sCR) was achieved in 7.8 percent of patients.

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Pembrolizumab – Keytruda- Shows Promise in Subset of Triple Negative Breast Cancer

MedicalResearch.com Interview with:

Sylvia Adams, MD Associate Professor of Medicine Breast Cancer and Cancer Immunotherapy Programs NYU Langone Medical Center Cancer Institute/Clinical Cancer Center New York, NY 10016

Dr. Adams

Sylvia Adams, MD
Associate Professor of Medicine
Breast Cancer and Cancer Immunotherapy Programs
NYU Langone Medical Center
Cancer Institute/Clinical Cancer Center
New York, NY 10016

 

MedicalResearch.com: What is the background for the Keynote-086 trial ? What are the main findings?

Response: This study is the largest immunotherapy study to date presented in metastatic triple negative breast cancer. This phase 2 trial studied the efficacy and safety of pembrolizumab (P) as single agent in a very aggressive disease and had two cohorts, a cohort of previously untreated patients (Cohort B) and a cohort with patients who had received prior chemotherapy lines in the metastatic setting (Cohort A).

The study showed that single agent pembrolizumab can elicit durable responses in a subset of patients. This was found regardless of tumoral PD-L1 expression but appeared to be much more frequent in women without prior chemotherapy treatments in the metastatic setting. Survival is especially promising for patients responding to therapy.

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Merkel Cell Carcinoma: Promising Treatment With Combination of T cells and PD-1 Blockade

MedicalResearch.com Interview with:
Dr. Kelly Garneski Paulson, MD, PHD
Fred Hutchinson Cancer Research Center
Seattle, WA  

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Merkel cell carcinoma (MCC) is an aggressive skin cancer with increasing impact. Currently, there are more than 2000 new cases of MCC diagnosed each year in the US. Over one third of patients will develop metastatic disease.

Most cases of Merkel cell carcinoma are caused by a virus (Merkel cell polyomavirus). In these cancers, the viral oncoproteins (cancer causing proteins) are highly expressed (exclusively on tumor tissue), immunogenic and are necessary for cancer growth.  These oncoproteins are thus ideal targets for cancer immunotherapy, making MCC a great cancer in which to study and develop immunotherapy.  Indeed, immunotherapies are effective in MCC, with observed response to checkpoint inhibitor mono therapy on the order of 35-55%, although complete responses remain rare.

In our first trial, we treated four patients with metastatic Merkel cell carcinoma with endogenous T cell therapy (ex vivo expanded polyclonal T cells recognizing Merkel cell polyomavirus). One patient developed a complete response, but three patients rapidly progressed. Interestingly, we observed that the patient with the complete response had low levels of PD-1 expression on the virus specific transferred T cells. We thus hypothesized adding adding an immune checkpoint inhibitor (avelumab, anti-PD-L1) to the transferred T cells would be acceptably safe and potentially improve clinical effectiveness.

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Report of Benign Moles Undergoing Immune Reaction During Nivolumab Therapy in a Patient With Melanoma

MedicalResearch.com Interview with:

Yasuhiro Nakamura, M.D., Ph.D. Associate Professor Department of Skin Oncology/Dermatology Comprehensive Cancer Center Saitama Medical University International Medical Center Hidaka, Saitama

Dr. Nakamura

Yasuhiro Nakamura, M.D., Ph.D.
Associate Professor
Department of Skin Oncology/Dermatology
Comprehensive Cancer Center
Saitama Medical University International Medical Center
Hidaka, Saitama

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Regressing nevi, which are frequently associated with halo phenomenon, occur in approximately 1% of the general population. In patients with melanoma, spontaneous or treatment-related depigmentation of the skin (vitiligo) is sometimes observed. Although humoral and cellular immune responses may play a crucial role in their development, immune reactions to benign melanocytic nevi (BMN) without a halo are extremely rare in both the general population and in patients with melanoma.

This publication reports a rare case with multiple metastatic melanomas who showed a remarkable clinical response to nivolumab with a simultaneous prominent immune reaction to multiple BMN without halo phenomenon. This rare phenomenon may be associated with dramatic efficacy of nivolumab in melanoma patients.

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Tofacitinib -XELJANZ: Potential New Treatment Option For Moderate To Severe Ulcerative Colitis

MedicalResearch.com Interview with:

William J. Sandborn, MD Professor of Medicine and Adjunct Professor of Surgery Chief, Division of Gastroenterology Vice Chair for Clinical Operations, Department of Medicine Director, UCSD IBD Center University of California San Diego and UC San Diego Health System

Dr. Sandborn

William J. Sandborn, MD
Professor of Medicine and Adjunct Professor of Surgery
Chief, Division of Gastroenterology
Vice Chair for Clinical Operations, Department of Medicine
Director, UCSD IBD Center
University of California San Diego and
UC San Diego Health System

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There is still a substantial unmet need for new treatments for patients with ulcerative colitis.

A previous Phase II study had suggested that tofacitinib might be effective for short term therapy of ulcerative colitis. The patients in that study for the most part had not failed anti-TNF therapy. Now we report the findings from 3 large Phase III trials, two short term trials and one long term trial, demonstrating that tofacitinib 10 mg twice daily is effective for short term therapy, and that both 5 mg and 10 mg twice daily is effective for long term therapy. We also demonstrated that tofacitinib is effective both in patients who have not failed anti-TNF therapy and patients who have failed anti-TNF therapy.

The study demonstrated induction of clinical remission, clinical response and mucosal healing (flexible sigmoidoscopy improvement) over the short term, and maintenance of clinical remission, clinical response, and mucosal healing over the long term.

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