Investigating the Efficacy of HPN217 in Relapsed/Refractory Multiple Myeloma With Luke Walker, MD

At the recent 64th American Society of Hematology (ASH) Annual Meeting in New Orleans, Dr. Luke Walker, Chief Medical Officer of Harpoon Therapeutics, sat down with Oncology Data Advisor to discuss the results of a phase 1 trial of HPN217, a B-cell maturation antigen (BCMA)–targeting T-cell engager, which were presented at the meeting. Dr. Walker delves into the efficacy that HPN217 demonstrated in patients with relapsed/refractory multiple myeloma, including its tolerability and low risk of cytokine release syndrome (CRS).  

This podcast episode was recorded live by Oncology Data Advisor and ConveyMED at the 2022 ASH Annual Meeting in New Orleans.

Oncology Data Advisor: Welcome to Oncology Data Advisor. We’re here at the ASH Annual Meeting today, and I’m with Dr. Luke Walker, who is the Chief Medical Officer of Harpoon Therapeutics. Thanks for joining today.

Luke Walker, MD: Thanks so much for having me.

Oncology Data Advisor: Would you like to tell us a little bit about yourself and your background?

Dr. Walker: Sure. I have been the Chief Medical Officer at Harpoon for about two months now. I joined most recently from Seagen, where I led the development of the tucatinib program, and then after that, led several of the pipeline antibody-drug conjugate (ADC) phase 1 programs. I’m really happy to be on board with Harpoon and the exciting science that we have there.

Oncology Data Advisor: So, today we’re talking about the phase 1 trial of HPN217 for multiple myeloma, which was presented here at ASH. Would you like tell us about this?

Dr. Walker: Sure. So, HPN217 is one of our programs built upon our Tri-Specific T-Cell–Activating Construct (TriTac®) technology. This is a bispecific technology that is designed to help minimize the risk of CRS and therefore try to maximize the therapeutic window by using single-domain antibody fragments for both the target antibody portion of the molecule, as well as for CD3. We also use an anti-albumin binding domain to help extend the half-life. HPN217, in particular, is targeted against BCMA. This study that we presented was a dose-escalation trial for patients with relapsed/refractory multiple myeloma who have received at least three prior therapies.

In this dataset, we had 62 patients. We were excited because last year at ASH, we presented an interim look as we were escalating the doses with fixed dosing. This time we were able to look at our highest step-dosing cohorts. We use a priming dose the first week, and then we used 12 mg or 24 mg for our target dosing. We’re exploring that both in a weekly and in an every-two-week fashion. With that, we saw a 77% response rate, with 46% of patients having a very good partial response (VGPR) or better. Importantly, we saw only 29% of patients having any CRS at all, and none of those patients had grade three. It was all grade one or two.

I think we’re seeing really exciting early data that would suggest a highly active compound that could potentially be differentiated in terms of its CRS intolerability. We think this is going to be really important as we look to develop this further in combination with other therapies and as we look to make sure that these types of therapies are accessible to patients in any kind of clinical setting. We’re excited to continue this trial. We hope to complete enrollment in the first half of next year and have a full dataset that would be available for us to go on to expansion in phase 2.

Oncology Data Advisor: That’s great. Anything else you’d like to share either about this study or about any other research that you might have seen here?

Dr. Walker: I think that we’re really happy about this as a validation to our platform. We also have this same platform that has target against DLL3, which is an active target that’s important for neuroendocrine carcinomas, including small cell lung carcinoma. We’re seeing early activity there as well. We really view the HPN217 story as validating for our TriTac® platform technology.

Within the myeloma space, I think that there are a lot of great data here and a lot of great opportunities for us to move the therapeutic options forward for patients. It’s a really exciting ASH conference, and I’m excited to see more data in the year ahead.

Oncology: Definitely. Thanks so much for talking about this today.

Dr. Walker: All right, thank you very much.

Thank you for listening to this podcast recorded live at the 2022 ASH Annual Meeting by Oncology Data Advisor and ConveyMED. For more expert perspectives on the latest in cancer research and treatment, be sure to subscribe to the podcast at and Don’t forget to follow us on social media for news, exclusive interviews, and more!

About Dr. Walker

Luke Walker, MD, is the Chief Medical Officer of Harpoon Therapeutics, where he leads clinical development strategy for novel T-cell engagers. A former practicing medical oncologist, Dr. Walker has an extensive background in overseeing global development of early-stage clinical programs and hematology/oncology drug development.

For More Information

Abdallah AO, Cowan AJ, Leleu X, et al (2022). Updated interim results from a phase 1 study of HPN217, a half-life extended Tri-specific T Cell Activating Construct (TriTac®) targeting B cell maturation antigen (BCMA) for relapsed/refractory multiple myeloma (RRMM). 64th American Society of Hematology Annual Meeting. Abstract 3240.

Transcript edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor. 

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