Bristol-Myers Squibb and Celgene Enter Clinical Collaboration Agreement to Evaluate Immunotherapy and Chemotherapy Combination Regimen
Phase I study to evaluate OPDIVO (nivolumab), Bristol-Myers Squibb’s investigational PD-1 immune checkpoint inhibitor, with Celgene’s ABRAXANE® for multiple cancers
Early clinical results with the drug, known as MPDL3280A, in so-called triple negative breast cancer will be revealed at the Dec. 9-13 San Antonio Breast Cancer Symposium.
Merck and Roche are hoping to widen this novel approach to treat advanced triple negative breast cancer, which is notoriously impervious to some of the most effective therapies available for breast cancer, like hormone therapy and drugs that target HER2 receptors. The New Jersey-based drugmaker and Swiss company will present early clinical results at the San Antonio Breast Cancer Symposium in December, according to Reuters.
Roche's drug, MPDL3280A, has already posted encouraging results in bladder, lung and skin cancers though it's not yet approved to treat any indications. Meanwhile, Merck is studying how triple negative breast cancer patients fair with its PD-1 drug Keyruda, which won approval for melanoma and has shown promise in stomach and other cancers.
Bristol-Myers is also moving in on this target, with its August announcement that it will begin a Phase I breast cancer trial of its PD-1 drug nivolumab alongside Celgene ($CELG) Abraxane.
Keytruda, has already been approved by the FDA for treating advanced melanoma. However, the drug showed promise in treating other cancers including triple-negative breast cancer (TNBC). TNBC is difficult to cure because it does not usually improve after using traditionally effective treatments such as hormone therapy. Merck hopes to change that with Keytruda.
The drug works by inhibiting a protein called programmed death receptor 1 (PD-1), which negatively regulates immune response. Tumors use PD-1 to avoid cells that fight against diseases. PD-1 blockers are a new class of immunotherapy drugs.
Caris Life Sciences Study Shows Molecular Profiling May Expand Use of PD-1 and PD-L1 Inhibitors to Wide Variety of CancersResults Published in Cancer Epidemiology Biomarkers & Prevention Demonstrate Utility of Caris Molecular Intelligence™ in Exploring Expression of Targetable Immune Proteins
PD-L1 and MEK inhibition may be synergistic in triple-negative breast cancer
MHC-I/II and PD-L1 expression appeared to have opposing effects on the immune system in patients with triple-negative breast cancer who had residual disease after neoadjuvant chemotherapy, according to study results presented at the San Antonio Breast Cancer Symposium.
These findings suggest that combined PD-L1 and MEK inhibition may have a synergistic antitumor effect in triple-negative breast cancer, researchers said.
“Increased tumor-infiltrating lymphocytes have been shown to predict favorable patient prognosis in triple-negative and HER-2–positive breast cancers in a variety of different disease states, including in the adjuvant setting,” Justin M. Balko, PharmD, PhD, assistant professor of medicine and cancer biology at Vanderbilt University in Nashville, Tenn., said during a presentation. “Increased tumor-infiltrating lymphocytes in pretreatment biopsies can also predict pathological complete response in the neoadjuvant setting, and in patients who lack a pathological complete response to neoadjuvant chemotherapy, increased tumor infiltrating lymphocytes in residual disease can predict improved RFS and OS.”
Thanks Donna. Such exciting news. I am in a different clinical trial for stage IV TNBC at Vanderbilt and so far, I have had complete response. I am excited to see other alternatives being developed, especially less toxic ones!
Found lump 9/16/11, age 55, Diagnosed 10/27 IDC TN, LX/SNB 12/7/11, Stage 1, Grade 3, 1.8 cm, 0/3 nodes, BRCA-, DD A/C on 1/23/12, followed by DD Taxol. 3/14/14 Stage IV, 3/26/14 Paclitaxel
Catwhispurrer, What clinical trial are you in? I have been in Roche/Genentech's MPDL3280A clinical trial for anti-PDL1 treatment and had a lot of progression on it and was taken off the trial. Thank you, Katrina
Early trial of new drug shows promise for patients with triple-negative breast cancer
In patients with metastatic triple-negative breast cancer—a disease with no approved targeted therapies—infusion of pembrolizumab produced durable responses in almost one out of five patients enrolled in a phase-Ib clinical trial, according to data presented Dec. 10, at the 2014 San Antonio Breast Cancer Symposium.
The multi-center, non-randomized trial was designed to evaluate the safety, tolerability and antitumor activity of bi-weekly infusions of pembrolizumab (MK-3475, marketed as Keytruda®). The researchers enrolled 27patients, aged 29 to 72 years, who had metastatic triple-negative breast cancer that either relapsed after treatment for early stage disease or progressed on therapy for advanced disease.
"For this group of patients our treatment options are limited to chemotherapy," said study director Rita Nanda, MD, assistant professor of medicine and associate director of the breast medical oncology program at the University of Chicago.
All patients in the study had triple-negative tumors with high levels of a protein called programmed death-ligand 1 (PD-L1). This protein can suppress the immune system's efforts to eliminate cancer cells. Pembrolizumab is a monoclonal antibody designed to help reactivate a person's own immune system to help fight the tumor.
"Pembrolizumab appears to make a significant difference for a subset of patients," Nanda said. "Of the 27 patients in this study with measurable disease, five (18.5%) had encouraging results. One patient had a complete response, and four had a partial response to treatment."
Responses for those five patients were long-lasting. Meanwhile, the patient with a complete response and two of those with a partial response continue to be treated with pembrolizumab.
An additional seven patients had stable disease, and twelve had progressive disease. Three patients left the trial early because their disease progressed.
Pembrolizumab, approved in September 2014 by the Food and Drug Administration for treatment of melanoma, does have some side effects. But Nanda said those are generally mild and easy to manage. They include fatigue, cough, nausea, itchy skin, rash, decreased appetite, constipation, joint pain and diarrhea.
In this trial, four of the 27 patients experienced at least one severe or life-threatening drug-related adverse event. One patient died while on the study treatment.
"The median survival for patients with triple-negative breast cancer is approximately one year," Nanda said. "We need better treatments for this disease. The promising activity of pembrolizumab seen in PD-L1-expressing, triple-negative breast cancer is exciting, and certainly worthy of further investigation."
An important next step, she said, is to learn how to predict which patients are most likely to benefit and how to manage the drug's toxicity.
Results of the first phase I trials of programmed cell death 1 (PD-1) and PD-L1 inhibitors in breast cancer were presented at the 2014 San Antonio Breast Cancer Symposium (SABCS), held December 9–13 in San Antonio, Texas. - See more at: http://www.cancernetwork.com/sabcs-2014/immunotherapy-yields-response-triple-negative-breast-cancer#sthash.ecVKpD4V.dpuf
A phase II trial of pembrolizumab in patients with advanced triple-negative breast cancer is expected to start in the first half of 2015. - See more at: http://www.cancernetwork.com/sabcs-2014/immunotherapy-yields-response-triple-negative-breast-cancer#sthash.ecVKpD4V.dpuf
Katrina - I am in a trial with Cisplatin and GDC-019 (Pi3K inhibitor) at Vanderbilt.
Found lump 9/16/11, age 55, Diagnosed 10/27 IDC TN, LX/SNB 12/7/11, Stage 1, Grade 3, 1.8 cm, 0/3 nodes, BRCA-, DD A/C on 1/23/12, followed by DD Taxol. 3/14/14 Stage IV, 3/26/14 Paclitaxel
In patients with metastatic triple-negative breast cancer--a disease with no approved targeted therapies--infusion of pembrolizumab produced durable responses in almost one out of five patients enrolled in a phase-Ib clinical trial, according to data presented at the 2014 San Antonio Breast Cancer Symposium.
The multi-center, non-randomized trial was designed to evaluate the safety, tolerability and antitumor activity of bi-weekly infusions of pembrolizumab (MK-3475, marketed as Keytruda®). The researchers enrolled 27 patients, aged 29 to 72 years, who had metastatic triple-negative breast cancer that either relapsed after treatment for early stage disease or progressed on therapy for advanced disease.
Is anyone familiar with CAR T-cell immune-therapy? It seems to be very successful for some other deadly cancers: http://www.cancer.gov/cancertopics/research-updates/2013/CAR-T-Cells. Someone said, "[The CAR T cells are] much more potent than anything we can achieve [with other immune-based treatments being studied]."
I also came across a trial of CAR-T for breast cancer. TNBC and metastatic BC can participate. Even newly diagnosed TNBC. Is anyone on this trial: https://clinicaltrials.gov/ct2/show/NCT01837602?
Rebecca
DX IDC TNBC May, 2014, 4.7cm, 5.8cm on Taxol. Taxol 4 weeks, AC 6. double mastectomy OCT 2014. 1.8cm residual in breast and 3mm a lymph node. BRCA-. 11/17 Abraxane,5FU.11/20, rads, 1/19 FUMEPx2
OncoSec Medical Plans to Initiate Pilot Study in Triple Negative Breast Cancer
Study to Be Conducted at Stanford University
OncoSec Medical Inc. (OTCQB: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, plans to initiate a pilot study to assess IL-12 ImmunoPulse in patients with Triple Negative Breast Cancer (TNBC). The study will be conducted at Stanford University with Melinda L. Telli, MD, serving as lead investigator.
This pilot study is designed to assess whether IL-12 ImmunoPulse increases TNBC tumor immunogenicity by driving a pro-inflammatory cascade of events that leads to increases in cytotoxic tumor-infiltrating lymphocytes (TILs). The presence and number of TILs is thought to be a key requirement for promoting the anti-tumor activity of antibodies like anti-PD-1/PD-L1. By driving cytotoxic immune cells into the tumor, IL-12 ImmunoPulse may be an ideal candidate to combine with checkpoint blockade therapies which reported some activity in TNBC.
Worldwide, TNBC amounts to approximately 200,000 cases each year and accounts for approximately 20 percent of all breast cancer. It is most commonly diagnosed in younger women (less than 40 years) and is characterized by higher relapse rates when compared with estrogen receptor (ER)-positive breast cancers. TNBC is also associated with an increased risk of recurrence, both locally and in distant sites, including the lung and brain. Advanced TNBC remains a significant area of unmet medical need and there is no established standard-of-care. Treatment generally includes chemotherapy, with or without radiation and/or surgery. However, no treatment regimen has clearly demonstrated superiority.
Previous studies have reported that patients with TNBC tumors associated with markers of inflammation, such as the presence of tumor-infiltrating lymphocytes (TILs), have improved survival, and recent data presented have shown that TNBC is responsive to immunotherapies like anti-PD-1 or anti-PD-L1 checkpoint blockade drugs. Response rates in TNBC patients receiving either anti-PD-1 or anti-PD-L1 in early Phase 1 studies were reported to be 18 to 33 percent.
“The data presented at the 2014 San Antonio Breast Cancer Symposium (SABCS), combined with historical data correlating increased immunogenicity with improved survival in TNBC, strongly suggest that treatments aimed at augmenting pro-inflammatory signals within the tumor have a central role in improving the clinical outcomes for TNBC patients,” said Mai H. Le, Chief Medical Officer at OncoSec Inc. “We are very excited to be working closely with our colleagues at Stanford on this pilot clinical program, which is specifically designed to evaluate the role of IL-12 ImmunoPulse in promoting tumor immunogenicity in TNBC and, ultimately, improving patient outcomes.”
Dr. Robert H. Pierce, OncoSec’s Chief Scientific Officer, commented: “Both the Merck and Roche/Genentech studies presented at SABCS indicate that a distinct sub-population of TNBC patients respond to inhibition of the immunosuppressive PD-1/PD-L1 axis. Both independent studies support the emerging paradigm that the presence of ‘stalled’ CD8 T cells (so called ‘adaptive resistance’) drives the response to PD-1/PD-L1 therapeutics. We are excited that two experts in this field, Drs. Holbrook Kohrt (Stanford) and Paul Tumeh (UCLA), will be involved in analyzing our samples from this pilot study.”
What a great thread with excellent information on immunotherapy. I'm trying to get on an immunotherapy trial at MD Anderson but so far no luck. It sounds so promising.
I ran across the following article. It's focused alot on melenoma but I found it interesting that some of these patient stories mention how it took awhile to actually see good results.
WOW!! I watched the video of each person and have a feeling that the immunotherapy trial is a winner for melanoma. The comment at the end from the man whose wife has stage 4 triple negative breast cancer really caught my eye. Wouldn't it be wonderful if it WORKS for us as well as for melanoma.
God Bless, Lillie
Dx 6/06 age 65,IDC-TNBC Stage IIb,Gr3,2cm,BRCA- 6/06 L/Mast/w/SNB,1of3 Nodes+ 6/06 Axl. 9 nodes- 8/8 thru 11/15 Chemo (Clin-Trial) DD A/Cx4 -- DD taxol+gemzar x4 No Rads. No RECON - 11/2018-12 yrs NED
Double WOW! Guess what the topic of conversation was today at lunchtime. Melanoma, stage iv triple negative breast cancer and YERVOY. A drug representative provided lunch for the doctors and staff. As I said the topic of conversation was YERVOY and a stage iv TN cancer patient. The oncologist and staff are hoping to get her insurance to give the go ahead with the Yervoy. I'm praying for NED for the lady who hopefully will be getting YERVOY.
God Bless, Lillie
Dx 6/06 age 65,IDC-TNBC Stage IIb,Gr3,2cm,BRCA- 6/06 L/Mast/w/SNB,1of3 Nodes+ 6/06 Axl. 9 nodes- 8/8 thru 11/15 Chemo (Clin-Trial) DD A/Cx4 -- DD taxol+gemzar x4 No Rads. No RECON - 11/2018-12 yrs NED
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