Trastuzumab Deruxtecan Safety in HER2-Expressing Solid Tumors With Funda Meric-Bernstam, MD

At the recent 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Funda Meric-Bernstam, the Department Chair in the Department of Vascular Cancer Therapeutics at MD Anderson Cancer Center, sat down with Oncology Data Advisor to discuss her presentation of the results of the Destiny-PanTumor-02 trial, in which her team studied the safety of trastuzumab deruxtecan on human epidermal growth factor receptor 2 (HER2)–expressing solid tumors.  

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, we’re here at the ASCO Annual Meeting and I’m joined by Dr. Meric-Bernstam. Thanks so much for coming on today.

Funda Meric-Bernstam, MD: Thank you for having me.

Oncology Data Advisor: Would you like to introduce yourself and share what your work and your research focus on?

Dr. Meric-Bernstam: I’m Funda Meric-Bernstam. I am the Department Chair in the Department of Vascular Cancer Therapeutics at MD Anderson Cancer Center. That is the Phase 1 Program where we explore novel therapies as well as do multi-histology basket trials with novel therapies.

Oncology Data Advisor: Great. So, you presented the results here of the Destiny-PanTumor-02 trial. What was the essential question that this trial was asking, and how does this fit with how patients have been treated for solid tumor so far?

Dr. Meric-Bernstam: Well, the recognition that HER2 is a valid clinical target has been known for several years, and of course there have been several drugs in development. Trastuzumab deruxtecan is a potent antibody-drug conjugate that already has been shown to be active for breast cancer that’s HER2-expressing, HER2-positive gastric cancer, and HER2-mutant lung cancer. The question we wanted to ask is whether it’s active in other tumor types with HER2 expression. So, this trial was conducted to look at patients that had HER2 expression at either 3+ or 2+ to look at the antigen efficacy.

Oncology Data Advisor: Can you briefly explain to our listeners what a basket trial is and what its implications are?

Dr. Meric-Bernstam: Well, it is hard to do trials when you recognize that some genomic alterations or some biomarkers may be expressed relatively infrequently in some diseases, maybe more frequently in other diseases. So, the approach of doing a basket trial allows for a single trial to be conducted to explore the signal across a variety of tumor types. In this particular clinical trial, we actually had disease-specific cohorts where we had six specific diseases where we know there was a relatively frequent expression of HER2. We looked at patients with gynecological diseases, cervical cancer, endometrial cancer, ovarian cancer, two gastrointestinal (GI) tumors, biliary cancer, and pancreatic cancer, and then we had a bladder cancer cohort. But in addition, we had a true basket, which is a disease-agnostic basket that allowed for us to enroll any tumor type that was HER2-positive, excluding the diseases I mentioned, and also excluding breast and gastric and lung cancer and colon cancer.

Oncology Data Advisor: Great. So, what have the interim results of the study shown so far?

Dr. Meric-Bernstam: The interim analysis reported on the primary end point, which was the objective response rate by investigator assessment. We enrolled 276 patients, and we demonstrated the objective response rate overall was 37%. This was a heavily pretreated population with a median of two prior lines of therapy, with 40% of the patients having three or more lines of therapy. So this is, I think, an exciting objective response rate. But also notable was that these were durable responses with a median duration of response of 11.8 months.

Oncology Data Advisor: That’s very exciting. What were the most common toxicities that were seen with the treatment?

Dr. Meric-Bernstam: Trastuzumab deruxtecan is already approved, therefore we know quite a bit about this drug already, so the safety of the drug and the side effect profile was similar to what’s been previously reported. And the most common grade 3 or greater side effects that we saw were neutropenia and anemia. There was one side effect of special note that we tracked, which is interstitial lung disease, and that occurred in 7.5% of the patients. Majority of those were low-grade; however, we did have one grade 5 toxicity.

Oncology Data Advisor: Okay, great. Have you found HER2 to be a compelling target, and should expression levels be tested in all solid tumors?

Dr. Meric-Bernstam: Yes, thanks for that question. Currently we know that HER2 expression is different at levels at different tumor types, and it’s not uniformly tested by all physicians. I think this data suggests that HER2 expression is a valid target in any tumor type where it is seen. I think further consideration should be to do HER2 testing in all solid tumors.

Oncology Data Advisor: Great. So, in this study, HER2 tumors are tested using immunohistochemistry. Do you think it will be feasible to test HER2 expression in a more convenient way in the future?

Dr. Meric-Bernstam: Well, immunohistochemistry is actually a fairly easy way to do it. So, immunohistochemistry is somewhat complex in that it’s well established for breast and gastric cancer, but it’s not routinely tested for other tumor types. However, most labs would have the capability of doing a immunohistochemistry chemistry. What we need to do is standardize how we do in immunohistochemistry as well as how we score immunohistochemistry for other tumor types. In this reduced trial, we used the gastric cancer scoring system for this. We also did note that patients that had high levels of HER2 had especially high levels of responses. The objective response rate was 61% in patients that were HER2 3+.

Oncology Data Advisor: Where do you plan to go from here with this research?

Dr. Meric-Bernstam: Yes, this is, I think, very interesting data and the activity was significant enough in some diseases to think about looking at the efficacy of a T-DXd in early settings.

Oncology Data Advisor: Great. My last question for you is—the theme of ASCO this year is Partnering with Patients—how do you strive to incorporate shared decision making with patients in your practice?

Dr. Meric-Bernstam: Yes, I think it’s really important for patients to be aware of targets like HER2, especially in diseases where HER2 is not commonly tested or not commonly expressed. So, it’s really important to make sure that there’s patient advocacy surrounding active testing for rarer targets and increased recognition of options available through clinical trials, as well as hopefully standard-of-care, too.

Oncology Data Advisor: Great. Thanks so much for stopping by to talk about these results. It’s very exciting to hear about.

Dr. Meric-Bernstam: Thank you.

About Dr. Meric-Bernstam

Funda Meric-Bernstam, MD, is the Department Chair of Investigational Cancer Therapeutics, a Phase 1 Program at MD Anderson Cancer Center. As well, Dr. Meric-Bernstam acts as the Medical Director of the Institute for Personalized Cancer Therapy (IPCT) and The Nellie B. Connally Chair in Breast Cancer, also at MD Anderson Cancer Center. Her research revolves around phase 1/2 trials that study drug response through novel combination therapies, mechanisms of action, and biomarkers.

For More Information

Meric-Bernstam F, Makker V, Oaknin A, et al (2023). Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) interim results. J Clin Oncol, 41(suppl_17). Abstract LBA3000. DOI:10.1200/JCO.2023.41.17_suppl.LBA3000

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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