ASCO 2018: Dr. Matt Davids on CLL Clinical Trials Open at Dana Farber Cancer Institute

In following up on our interview about the CLL research presented at ASCO 2018, Dr. Matt Davids from Dana Farber Cancer Institute (DFCI), Boston, MA shared two new trials for CLL patients building on what we have learned from ASCO and other published CLL research.

In my prior ASCO interview with Dr. Davids, he reviewed the data presented at ASCO 2018 from the CAPTIVATE trial that combined ibrutinib and venetoclax for frontline CLL therapy. There was a 100% response rate and 9/11 patients had no detectable disease (U-MRD).

Here is my interview with Dr. Jeff Jones done back in 2015 at ASH  where he presented the first non-chemo triplet to treat CLL: ibrutinib, venetoclax, and obinutuzumab.

We keep moving forward with the help of clinical trials.

DFCI is offering two exciting clinical trials:

• Based on the strong success of ibrutinib in combination with venetoclax in the CAPTIVATE trial, a trial of duvelisib and venetoclax (D+V) is open for relapsed refractory patients.
  • Duvelisib is a newly approved PI3K inhibitor and this is the first trial that combines a PI3K inhibitor with venetoclax, a very potent blocker of BCL-2 that leads to rapid CLL cell death.
  • There is good preclinical reason to believe this combination would be synergistic.
  • Both drugs are very active on their own but combining them offers the potential for any even more powerful non-chemo approach.
  • This might be a good option for patients who relapse after ibrutinib.
  • Treatment can be stopped if patients have no detectable disease (U-MRD) at one year.
• Acalabrutinib, venetoclax, and obinutuzumab (AVO) trial combines the BTK inhibitor acalabrutinib that may have a different side effect profile than ibrutinib with the BCL-2 blocker, venetoclax and obinutuzumab, the very powerful monoclonal antibody directed against CD20 found on CLL cells and normal B lymphocytes.
  • This is a similar triplet to the very potent combination of ibrutinib with venetoclax, and obinutuzumab.
  • This trial is for frontline treatment with the possibility of stopping all drugs at 15 months if U-MRD.

Here is a link to the D+V trial.

Here is a link to the AVO trial.

Comments:

These are just two of the many chronic lymphocytic leukemia trials involving novel agents. We will be presenting more open CLL trials and more trial results.

Research is rapidly moving in the direction of synergistic combinations of non-chemo drugs for a fixed duration that hold the promise of:

1. Lowering toxicities
2. Improving remissions
3. Decreasing the risk of developing resistance
4. Lowering cost of long-term medications

And these are all very good things.

Please enjoy my post ASCO 2018 interview with Dr. Davids.