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New daratumumab + Velcade + dex clinical trial

by Beacon Staff on Thu May 01, 2014 7:47 pm

Genmab, the company that initially developed the potential new myeloma therapy dara­tumu­mab, announced today in a press release that a Phase 3 trial of daratumumab plus Velcade and dexamethasone will be carried out.

It will be a large trial, including about 480 relapsed / refractory patients.

For patients who might be interested in participating in the trial, the primary downside is that this will be a randomized trial, meaning not all patients will receive the three-drug combination. Instead, patients will be randomly selected to receive either

- Daratumumab, Velcade, and dexamethasone, or
- Velcade and dexamethasone

No information about the trial is available yet at clinicaltrials.gov. Here, however, is a bit more detail from the Genmab press release:

Genmab A/S (OMX: GEN) announced today that its partner, Janssen Biotech, Inc. ("Janssen") will start a Phase III study of daratumumab in relapsed or refractory multiple myeloma. The study will compare daratumumab in combination with bortezomib and dexamethasone to bortezomib and dexamethasone alone.

"We have now announced plans for two Phase III studies of daratumumab in combination with the most common approved treatments for multiple myeloma. We believe that adding daratumumab to treatment regimens containing bortezomib, and lenalidomide, respectively, could potentially improve treatment outcomes for patients suffering from multiple myeloma," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the study
This Phase III study will include approximately 480 patients who have relapsed or refractory multiple myeloma. Patients will be randomized to receive either daratumumab combined with bortezomib (a unique type of chemotherapy, called a proteasome inhibitor) and dexamethasone (a corticosteroid), or bortezomib and dexamethasone alone. The primary endpoint of the study is progression free survival (PFS).

Beacon Staff

Re: New daratumumab + Velcade + dex clinical trial

by Multibilly on Thu May 01, 2014 8:08 pm

Beacon Staff,

You guys know much more about the evolution of clinical trials than I do.

The Phase 1/2 trial of daratumumab (who comes up with these names?) was for daratumumab as a sole agent, right?

In a couple of exchanges I had with patients in this trial, I thought they were having very good success with daratumumab as a sole agent ... with little or no side effects

Should I read anything into the fact that the Phase 3 trial is now combining Velcade and dex with daratumumab? Does this mean that daratumumab didn't meet their expectations as a sole agent? Or, is this just a normal progression in a clinical trial?

I was especially hopeful that we might be on the brink of having an MAB that could be used without other novel agents and dex ... and be spared these other drug's side effects.

Multibilly
Name: Multibilly
Who do you know with myeloma?: Me
When were you/they diagnosed?: Smoldering, Nov, 2012

Re: New daratumumab + Velcade + dex clinical trial

by Mark on Thu May 01, 2014 9:58 pm

Hi Multibilly,

Here is a link to the NCI website.

"Clinical trials to test new cancer treatments involve a series of steps, called phases. If a new treatment is successful in one phase, it will proceed to further testing in the next phase. During the early phases (phases 1 and 2), researchers figure out whether a new treatment is safe, what its side effects are, and the best dose of the new treatment. They also make sure that the treatment has some benefit, such as slowing tumor growth. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid."

http://www.cancer.gov/clinicaltrials/learningabout/what-are-clinical-trials/phases

Mark

Mark

Re: New daratumumab + Velcade + dex clinical trial

by Boris Simkovich on Thu May 01, 2014 9:59 pm

Hi Multibilly (and Mark),

I would not read anything into the announcement of the new trial.

Remember, Kyprolis (carfilzomib) was approved by the FDA based on data from a phase 2 trial that tested the drug as a single agent. There was only one group of patients in that study.

More importantly, even before the results of that trial were submitted to the FDA with the drug's marketing application, Onyx had started a number of other Kyprolis trials ongoing, testing the drug in combination with other agents.

It's the way things are done.

I believe that daratumumab will be filed with the FDA based on the data from the ongoing phase 2 trial testing it as a single agent in relapsed / refractory myeloma patients who have had at least three prior lines of therapy.

The phase 3 trials of daratumumab that are being planned -- like the one that was just announced -- most likely are being carried out to support applications for approval in Europe and other markets. In those areas of the world, regulatory agencies usually require large trials with two different groups of patients for a drug to be approved.

What I've just written is not based on any detailed research, so take it with a grain of salt. But I think it's a decent estimate of why the current trials are being carried out.

Boris Simkovich
Name: Boris Simkovich
Founder
The Myeloma Beacon

Re: New daratumumab + Velcade + dex clinical trial

by Multibilly on Fri May 02, 2014 6:12 am

Thanks Boris and Mark. Those responses were very helpful.

Multibilly
Name: Multibilly
Who do you know with myeloma?: Me
When were you/they diagnosed?: Smoldering, Nov, 2012


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