Merck 3475 in australia

I started that same Eap last May until it got fda approved here. I believe there was stuff in the paperwork about tumor growth and more tumors showing up. So that doesn't suprise me even on a Eap. Now that it is fda approved here it is up to my doc. They only gave me 3 doses and my first scan had 19 tumors shrinking but had 7 growing so they were only going to give me 2 more doses and scan again. Fortunately it got fda approved so I just had my 14th dose with most recent scan saying some tumors had mild growth.

I assume she is braf negative so those meds are not an option.

other than that the only options I know of are clinical trials. What I dunno but they are all at clinicaltrials.gov. It sounds like a yervoy pd1 trial could be good for her.

i wish I could be more help but I just dunno. Hopefully you can find a trial for her that works.

Artie

I started that same Eap last May until it got fda approved here. I believe there was stuff in the paperwork about tumor growth and more tumors showing up. So that doesn't suprise me even on a Eap. Now that it is fda approved here it is up to my doc. They only gave me 3 doses and my first scan had 19 tumors shrinking but had 7 growing so they were only going to give me 2 more doses and scan again. Fortunately it got fda approved so I just had my 14th dose with most recent scan saying some tumors had mild growth.

I assume she is braf negative so those meds are not an option.

other than that the only options I know of are clinical trials. What I dunno but they are all at clinicaltrials.gov. It sounds like a yervoy pd1 trial could be good for her.

i wish I could be more help but I just dunno. Hopefully you can find a trial for her that works.

Artie

I started that same Eap last May until it got fda approved here. I believe there was stuff in the paperwork about tumor growth and more tumors showing up. So that doesn't suprise me even on a Eap. Now that it is fda approved here it is up to my doc. They only gave me 3 doses and my first scan had 19 tumors shrinking but had 7 growing so they were only going to give me 2 more doses and scan again. Fortunately it got fda approved so I just had my 14th dose with most recent scan saying some tumors had mild growth.

I assume she is braf negative so those meds are not an option.

other than that the only options I know of are clinical trials. What I dunno but they are all at clinicaltrials.gov. It sounds like a yervoy pd1 trial could be good for her.

i wish I could be more help but I just dunno. Hopefully you can find a trial for her that works.

Artie

Hi Troy,

Not sure exactly what your wife's scans are showing…so that makes a difference.  But, the standards regarding what is known about a drug generally, is what defines the parameters of use, even in an EAP as far as I know.  Here is some data I have.  I don't know if you could use it as a starting place for a discussion with your wife's docs or not.

From ASCO, June 2014:

Evaluation of immune-related response criteria in patients with advanced melanoma treated with the anti-PD1 monoclonal antibody MK-3475
Abstract 3006, J Clin Oncol
Hodi, Ribas, Hamid, Robert, Weber, Wolchok, et al

3 melanoma cohorts treated with MK-3475 2mg/kg every 3 weeks, 10mg/kg every 3 OR 2 weeks in a phase 1 trial.  Tumor imaging was performed every 12 weeks.  411 patients enrolled.  192 were on MK-3475 for 28 weeks or more as of 10/18/2013.  Tumor flare was seen in 7 patients. In these patients, best overall response was:  complete response = 1, partial response = 4, stable disease = 2.  Atypical delayed response was seen in 6 patients.  The 51 patients with progressive disease, but also WITH evidence of response using immune criteria had favorable overall survival compared with 145 patients who had progressive disease and NO evidence of response via immune criteria.  Conclusion: Conventional criteria such as RECIST may underestimate the benefit of MK-3475 in approximately 10% of treated patients.

From: Overview of treatments for Melanoma Brain Metastases Novel Treatments for Melanoma Brain Metastases Kenchappa, Tran, Rao, Smalley, Gibney, Sondak, and Forsyth. October 2013.  Cancer Control.  "   

…Patience…[in monitoring clinical benefit] is required when using immunotherapies.  Early in the course of treatment, lesions may grow and become symptomatic, which is a pattern seen in systemic melanoma lesions treated with ipi, even though significant clinical response will ultimately occur.  In general, we attempt to wait until the end of the induction phase of ipi before concluding the presence of progressive disease.

It is pretty well accepted that immunotherapies (ipi as well as the anti-PD1 products) can produce a delayed response as well as some initial increase in size of tumors on scans due to inflammation and the process of necrosis, so waiting a bit longer for that to settle out, rather than removing patients from trials or EAP's is gradually becoming the norm, but something patients have to fight for at times.

I wish you and your wife well.  Celeste

Hi Troy,

Not sure exactly what your wife's scans are showing…so that makes a difference.  But, the standards regarding what is known about a drug generally, is what defines the parameters of use, even in an EAP as far as I know.  Here is some data I have.  I don't know if you could use it as a starting place for a discussion with your wife's docs or not.

From ASCO, June 2014:

Evaluation of immune-related response criteria in patients with advanced melanoma treated with the anti-PD1 monoclonal antibody MK-3475
Abstract 3006, J Clin Oncol
Hodi, Ribas, Hamid, Robert, Weber, Wolchok, et al

3 melanoma cohorts treated with MK-3475 2mg/kg every 3 weeks, 10mg/kg every 3 OR 2 weeks in a phase 1 trial.  Tumor imaging was performed every 12 weeks.  411 patients enrolled.  192 were on MK-3475 for 28 weeks or more as of 10/18/2013.  Tumor flare was seen in 7 patients. In these patients, best overall response was:  complete response = 1, partial response = 4, stable disease = 2.  Atypical delayed response was seen in 6 patients.  The 51 patients with progressive disease, but also WITH evidence of response using immune criteria had favorable overall survival compared with 145 patients who had progressive disease and NO evidence of response via immune criteria.  Conclusion: Conventional criteria such as RECIST may underestimate the benefit of MK-3475 in approximately 10% of treated patients.

From: Overview of treatments for Melanoma Brain Metastases Novel Treatments for Melanoma Brain Metastases Kenchappa, Tran, Rao, Smalley, Gibney, Sondak, and Forsyth. October 2013.  Cancer Control.  "   

…Patience…[in monitoring clinical benefit] is required when using immunotherapies.  Early in the course of treatment, lesions may grow and become symptomatic, which is a pattern seen in systemic melanoma lesions treated with ipi, even though significant clinical response will ultimately occur.  In general, we attempt to wait until the end of the induction phase of ipi before concluding the presence of progressive disease.

It is pretty well accepted that immunotherapies (ipi as well as the anti-PD1 products) can produce a delayed response as well as some initial increase in size of tumors on scans due to inflammation and the process of necrosis, so waiting a bit longer for that to settle out, rather than removing patients from trials or EAP's is gradually becoming the norm, but something patients have to fight for at times.

I wish you and your wife well.  Celeste

Hi Troy,

Not sure exactly what your wife's scans are showing…so that makes a difference.  But, the standards regarding what is known about a drug generally, is what defines the parameters of use, even in an EAP as far as I know.  Here is some data I have.  I don't know if you could use it as a starting place for a discussion with your wife's docs or not.

From ASCO, June 2014:

Evaluation of immune-related response criteria in patients with advanced melanoma treated with the anti-PD1 monoclonal antibody MK-3475
Abstract 3006, J Clin Oncol
Hodi, Ribas, Hamid, Robert, Weber, Wolchok, et al

3 melanoma cohorts treated with MK-3475 2mg/kg every 3 weeks, 10mg/kg every 3 OR 2 weeks in a phase 1 trial.  Tumor imaging was performed every 12 weeks.  411 patients enrolled.  192 were on MK-3475 for 28 weeks or more as of 10/18/2013.  Tumor flare was seen in 7 patients. In these patients, best overall response was:  complete response = 1, partial response = 4, stable disease = 2.  Atypical delayed response was seen in 6 patients.  The 51 patients with progressive disease, but also WITH evidence of response using immune criteria had favorable overall survival compared with 145 patients who had progressive disease and NO evidence of response via immune criteria.  Conclusion: Conventional criteria such as RECIST may underestimate the benefit of MK-3475 in approximately 10% of treated patients.

From: Overview of treatments for Melanoma Brain Metastases Novel Treatments for Melanoma Brain Metastases Kenchappa, Tran, Rao, Smalley, Gibney, Sondak, and Forsyth. October 2013.  Cancer Control.  "   

…Patience…[in monitoring clinical benefit] is required when using immunotherapies.  Early in the course of treatment, lesions may grow and become symptomatic, which is a pattern seen in systemic melanoma lesions treated with ipi, even though significant clinical response will ultimately occur.  In general, we attempt to wait until the end of the induction phase of ipi before concluding the presence of progressive disease.

It is pretty well accepted that immunotherapies (ipi as well as the anti-PD1 products) can produce a delayed response as well as some initial increase in size of tumors on scans due to inflammation and the process of necrosis, so waiting a bit longer for that to settle out, rather than removing patients from trials or EAP's is gradually becoming the norm, but something patients have to fight for at times.

I wish you and your wife well.  Celeste

I also have stage 4 and live in Sydney. I have been on Keytruda since last September. My tumours have shrunk and I had tried everything else before, including Dabrafenib and ipi and nothing worked.

Where are you located? What is a EAP? and is Merck 3475 Keytruda?

I'm just asking because I know they are continuing with clinical trials in NSW and now also in Victoria and Queensland. These trials are a combination of ipi (1 mg/kg) and nivolumab (3 ml/kg).

The doctors at Westmead in Sydney are simply amazing if you have a chance to get there.

Anne-Louise

I also have stage 4 and live in Sydney. I have been on Keytruda since last September. My tumours have shrunk and I had tried everything else before, including Dabrafenib and ipi and nothing worked.

Where are you located? What is a EAP? and is Merck 3475 Keytruda?

I'm just asking because I know they are continuing with clinical trials in NSW and now also in Victoria and Queensland. These trials are a combination of ipi (1 mg/kg) and nivolumab (3 ml/kg).

The doctors at Westmead in Sydney are simply amazing if you have a chance to get there.

Anne-Louise

I also have stage 4 and live in Sydney. I have been on Keytruda since last September. My tumours have shrunk and I had tried everything else before, including Dabrafenib and ipi and nothing worked.

Where are you located? What is a EAP? and is Merck 3475 Keytruda?

I'm just asking because I know they are continuing with clinical trials in NSW and now also in Victoria and Queensland. These trials are a combination of ipi (1 mg/kg) and nivolumab (3 ml/kg).

The doctors at Westmead in Sydney are simply amazing if you have a chance to get there.

Anne-Louise