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ASCO 2020 Top 12” #11: Clinical activity of cirmtuzumab, an anti-ROR1 antibody, in combination with ibrutinib: Interim results of a phase Ib/II study in mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL)

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In short videos with accompanying text, Dr. Brian Koffman, the Executive Vice President (EVP) and Chief Medical Officer (CMO) of the CLL Society, takes us through his “Top 12” abstracts from ASCO or the American Society of Clinical Oncology Annual Meeting held virtually in May, 2020.

#11

ASCO 2020: Clinical activity of cirmtuzumab, an anti-ROR1 antibody, in combination with ibrutinib: Interim results of a phase Ib/II study in mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL)

The holy grail in cancer research is to find a target on the cancer cells that is not found on normal tissue. ROR1 may be just such an antigen, an embryonic enzyme that is highly expressed on many hematologic cancers, including CLL and also on some solid cancers, but is not found on normal adult tissues. ROR1 promotes cancer growth and survival.

Cirmtuzumab is a humanized monoclonal antibody designed to block ROR1’s cancer promoting activities.

This study presents data on the combination of cirmtuzumab and ibrutinib in mantle cell lymphoma (MCL), a cousin B cell cancer to CLL, and in CLL.

We will only review the chronic lymphocytic leukemia data.

Takeaways:

  • 34 CLL patients were treated, with 12 being treatment naïve (TN) and 22 relapsed/refractory (R/R). Patients were excluded if they had received prior BTK inhibitor therapy.
  • The combo was well tolerated with no serious side effects.
  • 100% of the CLL patients responded, but there was only one complete response (CR).

Conclusion:

Ibrutinib has changed how we treat CLL, but it doesn’t finish the job. The hunt is on for its best tag team partner. Cirmtuzumab is appealing due to its safety and specificity, but whether it packs a sufficient punch remains to be proven. Given the dramatic results of ibrutinib when combined with venetoclax in several trials as outlined here in my interview with Dr. Nitin Jain or with obinutuzumab, where it has been approved by the FDA for frontline therapy based on its safety and efficacy, these 2 combos seem to be the frontrunners, and ROR1’s role in CLL treatment will need to be better clarified and defined. It seems as if it should be part of the mix, but how and where it will add to CLL care is still a work in progress.

Here is a link to the ASCO 2020 abstract: Clinical activity of cirmtuzumab, an anti-ROR1 antibody, in combination with ibrutinib: Interim results of a phase Ib/II study in mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL).

Here is more basic background on ROR1 and its promise by Dr. Choi, a leading cirmtuzumab and CLL researcher. It’s fun to see we use similar language in describing ROR1.

Stay strong.  We are all in this together.

Brian

Brian Koffman MDCM (retired) MS Ed
Co-Founder, Executive VP and Chief Medical Officer
CLL Society, Inc.