Medimmune PDL1 + MEK Trial?

Pat, as usual, you speak with great authority in the tone of your posts.  I'm curious where you've heard the rumors about the success of anti-PDL?  Have you met with any top melanona specialists or attended any conferences?  The last piece of information I recall seeing on anti-PDL was from MIF's report on the Society for Melanoma Research meeting in November:

"It didn't appear that PDL was as promising as initially thought from Sossman. more…later"

You know, Mat, one of the things I like best and value most about MPIP is that most of the people here (including you and me) "source" their information. If they got the info from a journal article they cite the journal. Or info from their doctor or from a news article, or whereever. I think this is extremely important so that the people who read the information have some idea about how much credibility to give it. I'm sure that we would all believe something printed in a peer-reviewed journal article more easily than we would believe something post on Joe Blow's blog. So, seriously, I do appreciate the extra effort that the members here put into sharing not only melanoma-related information but also where they got the information.

That's why I was careful to say that what I heard about anti-PDL-1 was only a rumor, i.e. it was not supported by published data. However, you are right– even a rumor should have a source, if possible. That info about anti-PDL-1 came from a post 6 months ago by Catherine Poole at the Melanoma International Foundation. She was then and remains today very enthusiastic about the possibile effectiveness of anti-PDL-1. I think that we are all anxiously awaiting the ASCO conference at the end of May to see some real data.

You know, Mat, one of the things I like best and value most about MPIP is that most of the people here (including you and me) "source" their information. If they got the info from a journal article they cite the journal. Or info from their doctor or from a news article, or whereever. I think this is extremely important so that the people who read the information have some idea about how much credibility to give it. I'm sure that we would all believe something printed in a peer-reviewed journal article more easily than we would believe something post on Joe Blow's blog. So, seriously, I do appreciate the extra effort that the members here put into sharing not only melanoma-related information but also where they got the information.

That's why I was careful to say that what I heard about anti-PDL-1 was only a rumor, i.e. it was not supported by published data. However, you are right– even a rumor should have a source, if possible. That info about anti-PDL-1 came from a post 6 months ago by Catherine Poole at the Melanoma International Foundation. She was then and remains today very enthusiastic about the possibile effectiveness of anti-PDL-1. I think that we are all anxiously awaiting the ASCO conference at the end of May to see some real data.

You know, Mat, one of the things I like best and value most about MPIP is that most of the people here (including you and me) "source" their information. If they got the info from a journal article they cite the journal. Or info from their doctor or from a news article, or whereever. I think this is extremely important so that the people who read the information have some idea about how much credibility to give it. I'm sure that we would all believe something printed in a peer-reviewed journal article more easily than we would believe something post on Joe Blow's blog. So, seriously, I do appreciate the extra effort that the members here put into sharing not only melanoma-related information but also where they got the information.

That's why I was careful to say that what I heard about anti-PDL-1 was only a rumor, i.e. it was not supported by published data. However, you are right– even a rumor should have a source, if possible. That info about anti-PDL-1 came from a post 6 months ago by Catherine Poole at the Melanoma International Foundation. She was then and remains today very enthusiastic about the possibile effectiveness of anti-PDL-1. I think that we are all anxiously awaiting the ASCO conference at the end of May to see some real data.

Very good points, Mat.  As someone who (along with most of the folks in my BMS anti-PD1 (Nivo) study at Moffitt) has had my tumor tested for the expression of PD-L1 on its surface…I have a very specific interest in the intel coming out about the anti-PDL1 drugs.   Back in 2012, The New England Journal of Medicine noted that in patients from a Nivo study, with a variety of tumor types, 25 of the 42 patients tested had tumors that were positive for PD-L1.  "Of these 25 patients, 9 had an objective response.  NONE of the 17 patients with PD-L1 NEGATIVE tumors had an objective response."  NOW…with that said….since then I have been told by the folks at Moffitt that that data was really important AND also told that it didn't mean so much after all.  We have still NOT been told what our personal tumors tested out to be…nor have I seen a report on that data.

________________________________________________________________________________

To back up a step here is a basic info report:  Promising drug prevents cancer cells from shutting down immune system  
31 May 2013 19:19:03 yale.edu

An investigational drug that targets the immune system’s ability to fight cancer is showing promising results in Yale Cancer Center (YCC) patients with a variety of advanced or metastatic forms of the disease. Updated data from this Phase 1 clinical trial are being formally presented at the 2013 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Yale Cancer Center is one of the lead trial sites. The abstract was made public by ASCO in advance of the meeting.

The drug, known as MPDL3280A and manufactured by Roche Genentech, is designed to prevent a cancer cell’s mutated and overexpressed PD-L1 gene protein from putting the immune system to sleep. The overexpressed PD-L1 protein turns off the immune system’s T-cells by binding to its PD-1 and B7.1 proteins. In doing so, it disguises itself and evades detection and destruction by the body’s immune response.

This new drug is the latest advance in the burgeoning field of immunotherapy, which aims to boost the body’s immune system to fight the foreign pathogens of cancer. By blocking the cancer tumor’s PD-L1 protein, MPDL3280A frees the immune system to do its job. This PD-L1 targeted antibody was specially engineered to increase safety and efficacy over earlier immunotherapy agents.

Yale oncologists report that the efficacy of MPDL3280A was evaluated in 140 patients with locally advanced or metastatic solid tumors who had exhausted other means of therapy. Tumor shrinkage was observed in patients with non-small cell lung cancer, melanoma, kidney cancer, colorectal cancer, and gastric cancer. Yale oncologists say ongoing, durable responses were observed in nearly all patients who responded to the drug. Overall, 29 out of 140 patients (21 percent) experienced significant tumor shrinkage, and the highest number of responses were in patients with lung cancer and melanoma.

MPDL3280A was generally well tolerated, they say, with few immune-related adverse events. Some patients were continuing to respond more than a year after starting treatment.

“We have been very impressed by the response in seriously ill patients whose cancer had metastasized. So far, almost none of those who showed tumor shrinkage have gotten worse, which is extraordinary,” said lead author Roy Herbst, M.D., professor of medicine and chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven. “Immunotherapy treatment is providing new hope for cancer patients,” he added.

_________________________________________________________________________________

Currently there is a Phase 2 study ongoing, using anti-PDL1 with avastin in renal cell carcinoma.  There is also a Phase 3 study in progess using anti-PDL1 in patients with non-small cell lung cancer.  Neither of these studie have published outcomes thus far…to my knowledge.

_________________________________________________________________________________

From ASCO, 2013:  A study of MPDL3280A (engineered anti-PDL1):  Activity, safety, and characterization of immune response in pre- and on-treatment tumors in metastatic melanoma patients.  Sosman, Hamid, Lawrense, Flaherty, Hodi, et al.

"Melanoma tumor cells may utilize PD-L1 overexpression to escape immune surveillance…In Phase 1 study, metastatic melanoma patients received MPDL3280A IV every 3 weeks for up to 1 year and had tumor assessments every 6 weeks.  As of Feb 2013, 44…patients dosed at 0.1-20mg/kg were evaluated…61% received >/= 1 prior systemic regimen and 36% received prior immunotherapy.  14% of patients experienced grade 3/4 treatment related adverse events, including [elevated liver enzymes].  No grade 3-5 pneumonitis or colitis was reported. 38…patients…dosed at 1-20mg/kg prior to August 2012 were evaluable…An objective response rate of 32% (11/34) was observed in patients with cutaneous, mucosal or unknown primary histology (0/4 ocular patients responded).  Resection of remaining mass in a responding patient after 1 year of therapy showed no evidence of viable tumor.  Responses were durable, with 10/11 ongoing (responding patients on study for 3-10.5 months).  Analysis of archival tumor samples showed that PD-L1 positive patients had a higher rate of disease control versus PD-L1 negative patients [87% vs 20%]."

_________________________________________________________________________________

Obviously, none of this addresses the combo discussed initially here.  But, with little info readily available, I thought some data on anti-PDL1 itself might be helpful.

Wishing you all my best.  Celeste

Very good points, Mat.  As someone who (along with most of the folks in my BMS anti-PD1 (Nivo) study at Moffitt) has had my tumor tested for the expression of PD-L1 on its surface…I have a very specific interest in the intel coming out about the anti-PDL1 drugs.   Back in 2012, The New England Journal of Medicine noted that in patients from a Nivo study, with a variety of tumor types, 25 of the 42 patients tested had tumors that were positive for PD-L1.  "Of these 25 patients, 9 had an objective response.  NONE of the 17 patients with PD-L1 NEGATIVE tumors had an objective response."  NOW…with that said….since then I have been told by the folks at Moffitt that that data was really important AND also told that it didn't mean so much after all.  We have still NOT been told what our personal tumors tested out to be…nor have I seen a report on that data.

________________________________________________________________________________

To back up a step here is a basic info report:  Promising drug prevents cancer cells from shutting down immune system  
31 May 2013 19:19:03 yale.edu

An investigational drug that targets the immune system’s ability to fight cancer is showing promising results in Yale Cancer Center (YCC) patients with a variety of advanced or metastatic forms of the disease. Updated data from this Phase 1 clinical trial are being formally presented at the 2013 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Yale Cancer Center is one of the lead trial sites. The abstract was made public by ASCO in advance of the meeting.

The drug, known as MPDL3280A and manufactured by Roche Genentech, is designed to prevent a cancer cell’s mutated and overexpressed PD-L1 gene protein from putting the immune system to sleep. The overexpressed PD-L1 protein turns off the immune system’s T-cells by binding to its PD-1 and B7.1 proteins. In doing so, it disguises itself and evades detection and destruction by the body’s immune response.

This new drug is the latest advance in the burgeoning field of immunotherapy, which aims to boost the body’s immune system to fight the foreign pathogens of cancer. By blocking the cancer tumor’s PD-L1 protein, MPDL3280A frees the immune system to do its job. This PD-L1 targeted antibody was specially engineered to increase safety and efficacy over earlier immunotherapy agents.

Yale oncologists report that the efficacy of MPDL3280A was evaluated in 140 patients with locally advanced or metastatic solid tumors who had exhausted other means of therapy. Tumor shrinkage was observed in patients with non-small cell lung cancer, melanoma, kidney cancer, colorectal cancer, and gastric cancer. Yale oncologists say ongoing, durable responses were observed in nearly all patients who responded to the drug. Overall, 29 out of 140 patients (21 percent) experienced significant tumor shrinkage, and the highest number of responses were in patients with lung cancer and melanoma.

MPDL3280A was generally well tolerated, they say, with few immune-related adverse events. Some patients were continuing to respond more than a year after starting treatment.

“We have been very impressed by the response in seriously ill patients whose cancer had metastasized. So far, almost none of those who showed tumor shrinkage have gotten worse, which is extraordinary,” said lead author Roy Herbst, M.D., professor of medicine and chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven. “Immunotherapy treatment is providing new hope for cancer patients,” he added.

_________________________________________________________________________________

Currently there is a Phase 2 study ongoing, using anti-PDL1 with avastin in renal cell carcinoma.  There is also a Phase 3 study in progess using anti-PDL1 in patients with non-small cell lung cancer.  Neither of these studie have published outcomes thus far…to my knowledge.

_________________________________________________________________________________

From ASCO, 2013:  A study of MPDL3280A (engineered anti-PDL1):  Activity, safety, and characterization of immune response in pre- and on-treatment tumors in metastatic melanoma patients.  Sosman, Hamid, Lawrense, Flaherty, Hodi, et al.

"Melanoma tumor cells may utilize PD-L1 overexpression to escape immune surveillance…In Phase 1 study, metastatic melanoma patients received MPDL3280A IV every 3 weeks for up to 1 year and had tumor assessments every 6 weeks.  As of Feb 2013, 44…patients dosed at 0.1-20mg/kg were evaluated…61% received >/= 1 prior systemic regimen and 36% received prior immunotherapy.  14% of patients experienced grade 3/4 treatment related adverse events, including [elevated liver enzymes].  No grade 3-5 pneumonitis or colitis was reported. 38…patients…dosed at 1-20mg/kg prior to August 2012 were evaluable…An objective response rate of 32% (11/34) was observed in patients with cutaneous, mucosal or unknown primary histology (0/4 ocular patients responded).  Resection of remaining mass in a responding patient after 1 year of therapy showed no evidence of viable tumor.  Responses were durable, with 10/11 ongoing (responding patients on study for 3-10.5 months).  Analysis of archival tumor samples showed that PD-L1 positive patients had a higher rate of disease control versus PD-L1 negative patients [87% vs 20%]."

_________________________________________________________________________________

Obviously, none of this addresses the combo discussed initially here.  But, with little info readily available, I thought some data on anti-PDL1 itself might be helpful.

Wishing you all my best.  Celeste

Thanks Celeste.  I appreciate your blog–lots of useful information.

Thanks Celeste.  I appreciate your blog–lots of useful information.

Thanks Celeste.  I appreciate your blog–lots of useful information.

Very good points, Mat.  As someone who (along with most of the folks in my BMS anti-PD1 (Nivo) study at Moffitt) has had my tumor tested for the expression of PD-L1 on its surface…I have a very specific interest in the intel coming out about the anti-PDL1 drugs.   Back in 2012, The New England Journal of Medicine noted that in patients from a Nivo study, with a variety of tumor types, 25 of the 42 patients tested had tumors that were positive for PD-L1.  "Of these 25 patients, 9 had an objective response.  NONE of the 17 patients with PD-L1 NEGATIVE tumors had an objective response."  NOW…with that said….since then I have been told by the folks at Moffitt that that data was really important AND also told that it didn't mean so much after all.  We have still NOT been told what our personal tumors tested out to be…nor have I seen a report on that data.

________________________________________________________________________________

To back up a step here is a basic info report:  Promising drug prevents cancer cells from shutting down immune system  
31 May 2013 19:19:03 yale.edu

An investigational drug that targets the immune system’s ability to fight cancer is showing promising results in Yale Cancer Center (YCC) patients with a variety of advanced or metastatic forms of the disease. Updated data from this Phase 1 clinical trial are being formally presented at the 2013 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Yale Cancer Center is one of the lead trial sites. The abstract was made public by ASCO in advance of the meeting.

The drug, known as MPDL3280A and manufactured by Roche Genentech, is designed to prevent a cancer cell’s mutated and overexpressed PD-L1 gene protein from putting the immune system to sleep. The overexpressed PD-L1 protein turns off the immune system’s T-cells by binding to its PD-1 and B7.1 proteins. In doing so, it disguises itself and evades detection and destruction by the body’s immune response.

This new drug is the latest advance in the burgeoning field of immunotherapy, which aims to boost the body’s immune system to fight the foreign pathogens of cancer. By blocking the cancer tumor’s PD-L1 protein, MPDL3280A frees the immune system to do its job. This PD-L1 targeted antibody was specially engineered to increase safety and efficacy over earlier immunotherapy agents.

Yale oncologists report that the efficacy of MPDL3280A was evaluated in 140 patients with locally advanced or metastatic solid tumors who had exhausted other means of therapy. Tumor shrinkage was observed in patients with non-small cell lung cancer, melanoma, kidney cancer, colorectal cancer, and gastric cancer. Yale oncologists say ongoing, durable responses were observed in nearly all patients who responded to the drug. Overall, 29 out of 140 patients (21 percent) experienced significant tumor shrinkage, and the highest number of responses were in patients with lung cancer and melanoma.

MPDL3280A was generally well tolerated, they say, with few immune-related adverse events. Some patients were continuing to respond more than a year after starting treatment.

“We have been very impressed by the response in seriously ill patients whose cancer had metastasized. So far, almost none of those who showed tumor shrinkage have gotten worse, which is extraordinary,” said lead author Roy Herbst, M.D., professor of medicine and chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven. “Immunotherapy treatment is providing new hope for cancer patients,” he added.

_________________________________________________________________________________

Currently there is a Phase 2 study ongoing, using anti-PDL1 with avastin in renal cell carcinoma.  There is also a Phase 3 study in progess using anti-PDL1 in patients with non-small cell lung cancer.  Neither of these studie have published outcomes thus far…to my knowledge.

_________________________________________________________________________________

From ASCO, 2013:  A study of MPDL3280A (engineered anti-PDL1):  Activity, safety, and characterization of immune response in pre- and on-treatment tumors in metastatic melanoma patients.  Sosman, Hamid, Lawrense, Flaherty, Hodi, et al.

"Melanoma tumor cells may utilize PD-L1 overexpression to escape immune surveillance…In Phase 1 study, metastatic melanoma patients received MPDL3280A IV every 3 weeks for up to 1 year and had tumor assessments every 6 weeks.  As of Feb 2013, 44…patients dosed at 0.1-20mg/kg were evaluated…61% received >/= 1 prior systemic regimen and 36% received prior immunotherapy.  14% of patients experienced grade 3/4 treatment related adverse events, including [elevated liver enzymes].  No grade 3-5 pneumonitis or colitis was reported. 38…patients…dosed at 1-20mg/kg prior to August 2012 were evaluable…An objective response rate of 32% (11/34) was observed in patients with cutaneous, mucosal or unknown primary histology (0/4 ocular patients responded).  Resection of remaining mass in a responding patient after 1 year of therapy showed no evidence of viable tumor.  Responses were durable, with 10/11 ongoing (responding patients on study for 3-10.5 months).  Analysis of archival tumor samples showed that PD-L1 positive patients had a higher rate of disease control versus PD-L1 negative patients [87% vs 20%]."

_________________________________________________________________________________

Obviously, none of this addresses the combo discussed initially here.  But, with little info readily available, I thought some data on anti-PDL1 itself might be helpful.

Wishing you all my best.  Celeste

Pat, as usual, you speak with great authority in the tone of your posts.  I'm curious where you've heard the rumors about the success of anti-PDL?  Have you met with any top melanona specialists or attended any conferences?  The last piece of information I recall seeing on anti-PDL was from MIF's report on the Society for Melanoma Research meeting in November:

"It didn't appear that PDL was as promising as initially thought from Sossman. more…later"

Pat, as usual, you speak with great authority in the tone of your posts.  I'm curious where you've heard the rumors about the success of anti-PDL?  Have you met with any top melanona specialists or attended any conferences?  The last piece of information I recall seeing on anti-PDL was from MIF's report on the Society for Melanoma Research meeting in November:

"It didn't appear that PDL was as promising as initially thought from Sossman. more…later"