Pashtoon Kasi, MD, MS - Cancer Therapy Advisor

How Recent Adaptations to Clinical Trials Could Help Cancer Research: Innovation at SITC 2020

Meeting Insights
Pashtoon Kasi, MD

 

How Recent Adaptations to Clinical Trials Could Help Cancer Research: Innovation at SITC 2020

Pashtoon Kasi, MD, MS

Pashtoon Kasi, MD, MS

Practice Community

Iowa City, Iowa

Practice Niche

Gastrointestinal Cancers

Hospital and Institutional Affiliations

University of Iowa Health Care

This interview has been condensed and lightly edited for clarity.

Question

What were the most compelling data coming out of the Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020), in your view?

Answer

This year, some of the key advances I was looking for out of SITC involved discoveries related to better biomarkers in terms of immune checkpoint inhibitors (ICIs) and other targeted treatments.

The other big subject that is always of value are early-phase studies of bispecific antibodies. These are novel drugs that are not just a monoclonal antibody and an immunotherapy, but drugs that have 1 end attacking the tumor and the other end attracting the immune cells. Additionally, it is always interesting to see data from studies that are refining immunotherapy for tissue types that do not traditionally see efficacy from immunotherapeutic approaches.

Question

Research out of SITC 2020 showed that neoadjuvant treatment with chemotherapy plus nivolumab resulted in a greater frequency of downstaging in non-small cell lung cancer (NSCLC) compared with chemotherapy or ICI treatment alone.1 What is your view of the use of ICIs in this setting?

Answer

These results are interesting to see, not just for NSCLC, but also for some other tumor types. It used to be that immunotherapy and chemotherapy were considered separate entities, with patients treated with 1 or the other. For many tumor types, including esophageal cancer, data are showing that this may not be the case. These 2 treatments may be complementary.

There have been insights showing that chemotherapy may not only affect the cancer in terms of shrinking the tumor or whatever specific mechanism of action it has, but that chemotherapy itself may also be affecting the person’s immune system as well. There is an imbalance of immune cells in certain individuals where ICIs don’t work. We now are seeing that there are other factors or other players in the microenvironment that may have a role, and chemotherapy may overcome that particular barrier. It is not surprising that the combination fared better than either alone.

Question

There were many plans announced of trials that will begin or are in progress, especially in renal cell carcinoma (such as COSMIC-313), but perhaps most interesting is a study that found that there were racial differences in outcomes for patients with renal cell carcinoma (RCC) who were administered ICIs.2 Should trials in RCC be adjusted to account for these ethnic/racial differences that are found? How can oncologists start to do that?

Answer

It is interesting but not surprising. Immunotherapy drugs directly rely on the patient’s immune system, and we know that not just race, but also sex and other variables, play a role in the metabolism of drugs. From a [trial] design standpoint, it should not be difficult to better incorporate race or ethnicity into clinical trials. The National Institutes of Health mandates that NIH-sponsored trials at these cancer centers include a certain proportion of women and minorities. Additionally, they follow up to see if the proportion planned for enrollment holds up in the actual trials. For example, if the center in practice sees more African Americans for a disease type, but in the trials, the numbers are the opposite — that is a red flag.

Information on race/ethnicity is collected for many clinical trials, so these findings may prompt reanalysis of already-published data.

Question

CPI-006, a B-cell activating antibody originally under development as an anticancer therapy, showed early efficacy as a potential treatment for coronavirus disease 2019 (COVID-19).3 Are you surprised to think that a cancer immunotherapy might have utility as a treatment for COVID-19? Why or why not?

Answer

I am not surprised. As we deal with drugs like immunotherapies and targeted therapies, it is not surprising that these may have effects on the SARS-CoV-2 virus or any other infection. One historical example involves lymphoma and HIV. There was always a concern about whether immunotherapy might be a contraindication in patients with lymphoma and HIV, but now there are trials that show that immunotherapy can be incorporated into treatment and may have positive consequences on the person’s infection. Similar things have been shown with hepatitis C and liver cancer.

Some cancer drugs may share targets that may be analogous with the virus itself. It is definitely something that is actively being considered.

Question

Speaking of vaccines, there were many presentations at the meeting on vaccines for cancer (glioblastoma, melanoma, etc.).4,5 What are some strategies in vaccine development that oncology researchers can learn from in the quest for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine?

Answer

The biggest thing to learn relates to the fact that everybody was so invested in this question. Every week there are more developments in the area of SARS-CoV-2 vaccines.

There is nothing good about this pandemic, but from a research and systems perspective, we have learned a lot. For example, the explosion of the use of telemedicine and having that be a replacement for an in-person visit … we never saw that happening on the scale that it is now. State boundaries for telemedicine have also been expanded. I have been able to see patients from out of state. Clinical trials have also adapted, with industry sponsors eliminating the need for so many on-site evaluations.

It takes a mean of 16 or more years for things to make [their] way from the lab to the clinic. Here we are, and it hasn’t even been 16 months, and we have vaccines against this virus. That is a refreshing thing. This type of research and development is expensive, and there was an active investment of grant money. It would be great if this type of advocacy and support could be applied to some rare subtypes of tumors. If these and many of the other advances that have taken place as a result of the pandemic can be carried forward it would be a big advancement for medicine.

References

  1. Sepesi B, Corsini EM, Weissferdt A, et al. Combined neoadjuvant chemo-immunotherapy therapy achieves superior downstaging of resectable non-small cell lung cancer as compared to chemotherapy, mono or dual immunotherapy. Presented at: Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020); November 11-14, 2020. Abstract 277. J Immunother Cancer. 2020;8(Suppl 3):A656–A959.
  2. Olsen TA, Martini DJ, Goyal S, et al. Racial differences in outcomes for metastatic renal cell carcinoma (mRCC) patients managed on immune-checkpoint inhibitor (ICI) therapy. Presented at: Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020); November 11-14, 2020. Abstract 223. J Immunother Cancer. 2020;8(Suppl 3):A656–A959.                           
  3. Criner GJ, Mobasher M, Hill GM, et al. Immunotherapy with B cell activating antibody CPI-006 in patients (pts) with mild to moderate COVID-19 stimulations anti-SARS-CoV-2 antibody response, memory B cells and memory T effector cells. Presented at: Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020); November 11-14, 2020. Abstract 325. J Immunother Cancer. 2020;8(Suppl 3):A656–A959.
  4. Marron TU, Kodysh J, Rubinsteyn A, et al. PGV-001: A phase 1 trial of a personalized neoantigen peptide vaccine for the treatment of malignancies in the adjuvant setting. Presented at: Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020); November 11-14, 2020. Abstract 289. J Immunother Cancer. 2020;8(Suppl 3):A656–A959.
  5. Bota DA, Piccioni DE, Duma CD, et al. Phase II trial of immunotherapy in primary glioblastoma: antigens from self-renewing autologous tumor cells presented by autologous dendritic cell vaccine. Presented at: Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020); November 11-14, 2020. Abstract 319. J Immunother Cancer. 2020;8(Suppl 3):A656–A959.