Stephanie Comello:Please could you describe the study and the clinical data?
Professor Sergei Krasny: The clinical protocol for the original study was developed by an international team that included oncologists from Belarus National Cancer Center and Minsk City Oncology Center, together with colleagues from MD Andersen Cancer Center, NYU, and Thomas Jefferson University.
A higher number of patients will be necessary to conclude the effect with statistical confidence. Possibly due to the COVID pandemic, enrollment into the study has been much slower than expected and what was seen in our other studies prior to 2020. Still, if similar results are seen as the study continues, the addition of Elenagen shows great promise to helping manage triple negative breast cancer and platinum resistant ovarian cancer patients.
Finally, it is important to mention a very strong safety profile of Elenagen. If we combine the number of patients who received Elenagen in our study with the number of patients receiving Elenagen in a previously published phase I/IIa study, the total exceeds 100 patients. The corresponding data shows none developed a serious adverse reaction.
We randomized patients diagnosed with metastatic triple-negative breast cancer into two groups. Patients in the control group received standard CMF chemotherapy: Cyclophosphamide 600 mg/m2 + Methotrexate 40mg/m2 + Fluorouracil 600mg/m2administered IV, on day 1 and day 8, which is repeated every 4 weeks. Patients in the experimental group received the same chemotherapy plus p62-encoded plasmid, Elenagen™ IM once a week at a rate of 2.5 mg per injection. The efficacy of the treatment is assessed according to the RECIST 1.1 criteria. The toxicity of the treatment is documented according to CT CAE version 4.0.
What really got our attention: when Elenagen was added to the treatment regimen, all patients showed complete or partial regression of the primary tumor and associated metastases in the lungs, liver, lymph nodes, and bones.
In two Elenagen-treated patients, a radical operation was performed, and no tumor cells were found in the removed material. All patients continued to receive Elenagen per the above protocol. So far, only one patient showed disease progression, which started 42 weeks after starting treatment.
In contrast, 50% of patients receiving standard chemotherapy demonstrated disease progression at week 26. The difference between the groups was shown to be statistically significant (p = 0.049).
In the picture above, you can see a complete response in a patient before and after six months of treatment with CMF plus Elenagen. Both the primary tumor and the metastases are visible in the upper panel before the treatment, while they are fully regressed in the bottom panel, presumably due to the Elenagen combination treatment.
Another study arm includes platinum-resistant ovarian cancer patients. Patients are randomized 1:1 to receive either Gemcitabine alone, 1000 mg/m2 on day 1 and 8 of a treatment course, then repeated every 3 weeks; or Gemcitabine using the same administration protocol in a combination with Elenagen at the same dosage as in the breast cancer arm of the study.
Our initial results suggest the patients could see a doubling of the progression-free survival time. In some patients, a partial response was registered such as reduced tumor and metastatic lesions, which meant the patient became a candidate for operable surgery.
Thus, we are continuing our study with cautious optimism.
Stephanie Comello: What are the most common questions your colleagues asked you about the study?
Dr. Alexander Shneider: The two most frequent questions we encounter are:
1. Why CMF? Well, the answer is because for triple-negative breast cancer, it remains to be one of the best and is not surpassed by anything else.
2. Are we planning to combine it with other immune therapeutic modalities? The answer is yes—to all these immune therapeutic modalities.
But first, let me answer the question: What is Elenagen? It’s a plasmid-encoding protein called p62/SQSTM1. Also, we don't plan to use Elenagen as a monotherapy. So, in the study which Sergei presented, we combined it with CMF for triple-negative breast cancer patients.
Perhaps the second question, which we hear the most often, is if we plan to combine Elenagen with immune therapies: checkpoint inhibitors, CAR-Ts, and other immune therapies. And the answer is “yes.” We expect great synergistic effect. Elenagen increases the number of TILs, tumor infiltrating lymphocytes, making the tumors “hot.”
Also, it changes tumor microenvironment making immune response more effective inside the tumor. Finally, Elenagen reduces chronic inflammation, which is (in contrast to an acute inflammation) is immunosuppressive. We have published and unpublished data supporting these ideas.
Stephanie Comello: Will this data affect clinicians today? If so, how?
Dr. Alexander Shneider: I would name two ways. First, looking at our data, oncologists may decide to join our clinical study. We are very open to collaborations. We don't care about geographical locations. We don't care about the prestige of different medical centers.
And the second element of this question is—and this part will be US-centric because I know US law, and I’m not as familiar with other countries—it’s about the Right to Try. Obviously, the Right to Try is a great piece of legislation because many cancer patients who need it today will not live long enough to see benefits of all these registration procedures.
That is why the US government gave clinicians and patients the Right to Try, if the company is open to that. And yes, CureLab Oncology is 100% open for this kind of collaboration with patients who need it and clinicians who are patient-focused and patient-centered.
Dr. Alexander Shneider: I view it as a multi-dimensional journey. The first dimension is to finish ongoing clinical studies (which Sergei presented) and to commence clinical trials, phase two, for triple-negative breast cancer and platinum-resistant ovarian cancer here in the United States.
Also, we are really thankful to our colleagues in Belarus who are now including more groups in the study, for example, hormone-resistant metastatic prostate cancer and hormone-resistant breast cancer. Of course, we are using Elenagen in combination with standard of care. And for each disease we need to find an optimal combination of Elenagen with other treatment modalities, and the optimal regimen.
Stephanie Comello: Is there anything else you can think medical oncologists and hematologists need to know about this data?
Dr. Alexander Shneider: I would like to send a message of quality of life focus in addition to other standard metrics, which are the biggest focus during this study and all the future studies. Due to the mechanism of action—because Elenagen reduces chronic inflammation and certain mechanisms involved in pain—we may be increasing quality of life of a patient making this part—perhaps the last part—of patient's life comfortable. This is very important to me as a human.