Friday marks the start of the largest cancer research conference in the world. The American Society of Clinical Oncology (ASCO) annual meeting takes place June 1-5 at its traditional home in Chicago’s McCormick Place convention facility. Meetings like this are important because they are where companies and other researchers aim to share the latest results of clinical trials for medicines in development. If you have an important trial result in cancer to announce, there is no bigger stage than ASCO to do it. Physicians, researchers, and a myriad of others who are interested in cancer care travel from all over the world to be a part of this big event.
We are pleased to see that ASCO has named adoptive cell immunotherapy as the clinical cancer Advance of the Year for 2018. The most famous type of adoptive cell immunotherapy is CAR-T. This is where a patient’s T-cells are re-engineered outside of the body with the goal of making them better able to recognize and kill cancer. FDA approved the first of these treatments in August of 2017 for a type of childhood leukemia and two others have since been approved for types of B-cell lymphoma in adults. CNCR invests in CAR-T leaders like Bellicum, bluebird bio, Cellectis, Gilead, Novartis, and ZIOPHARM Oncology.
The Cancer Immunotherapy ETF (Nasdaq: CNCR) prepares extensively for ASCO since many of the fund’s underlying holdings are scheduled to present research there. We do this not only to prepare ourselves, but also as a service to our investors and other readers. Sharing research and making CNCR an educational tool about immunotherapy is something that is important to us and we hope you find value in it. With that in mind, here are a handful of upcoming ASCO presentations we found to be particularly interesting. We hope you enjoy following along as news happens at the meeting.
bluebird bio (Nasdaq: BLUE)
bb2121 anti-BCMA CAR T-cell therapy in patients with relapsed/refractory multiple myeloma: Updated results from a multicenter phase I study.
We mentioned above that adoptive cell immunotherapy (like CAR-T) was named the advance of the year by ASCO for 2018. Part of the credit for this belongs to a boost the field received at last year’s ASCO when bluebird and others announced promising initial results by engineering the BCMA target into their CAR-T treatments and using it against a type of cancer that highly expresses BCMA called multiple myeloma. Before then, CAR-T treatments had only been working against certain blood cancers that expressed a protein called CD19. To see that multiple myeloma patients were responding to BCMA CAR-T was an important finding that suggests CAR-T might have utility beyond CD19.
However, companies like bluebird still have a lot to prove before we know whether BCMA CAR-T might be approvable by FDA and competitive with other treatments. Bluebird has only tested its BCMA CAR-T in a handful of patients up to this point and we do yet not know the full safety and efficacy profile of the treatment. For example, we want to have a better understanding of how durable patient responses are over time. With each meeting that happens where more data is presented, the picture becomes clearer. Bluebird last presented BCMA CAR-T data covering 21 patients at a conference called ASH back in December. At ASCO, we will receive an important update on how those patients are doing as well as early data from new ones who were treated in a more advanced phase of the trial.
Bluebird will be webcasting an investor and analyst call to discuss ASCO data on Friday, June 1st at 6:30 PM CDT. More info about that can be found on the investor relations section of the company’s website.
Nektar Therapeutics (Nasdaq: NKTR)
NKTR-214 (CD122-biased agonist) plus nivolumab in patients with advanced solid tumors: Preliminary phase 1/2 results of PIVOT
Nektar made a splash in the cancer immunotherapy research community back in November when the company first presented data for its immunotherapy drug NKTR-214 in combination with Bristol-Myers Squibb’s nivolumab in melanoma, non-small cell lung cancer, and renal cell carcinoma. After the company’s market valuation increased by approximately $7.5 billion in the weeks after, we published a research report describing why the initial data appeared to be compelling. Since then, Bristol signed a landmark collaboration with Nektar in February to further develop these drugs together. Bristol paid $1.85 billion up front, which included $1 billion in cash and the purchase of approximately 8.28 million shares of Nektar stock at $102.60 per share.
Please read our previous research to gain a more in-depth understanding of the mechanism of NKTR-214. However, the main idea is that the drug aims to proliferate (grow) immune cells in tumors and also to increase the expression of a protein called PD-L1. The idea is that this might boost the efficacy of checkpoint inhibitor therapies like Bristol’s nivolumab because they work by latching onto PD-L1 and allowing the immune system to attack. We call this “taking the breaks off the immune system” and it does not succeed if there are too few immune cells in the area or if there is not enough PD-L1 expression to set off the mechanism. Therefore, the goal of NKTR-214 is to create the right environment to maximize the success of these existing drugs.
As mentioned, we first saw data from the combination of NKTR-214 and nivolumab in melanoma, non-small cell lung cancer, and renal cell carcinoma back in November. A new update was published on May 16th when initial abstract data was released for ASCO. This may 16th release included data from 162 patients across those three initial cancers as well as triple-negative breast cancer and bladder cancer. Nektar mentioned that the data was collected as of February 7th and that we will see a more recent update at the ASCO conference itself. With more patient data and across a longer period of time, this will give a better glimpse into the efficacy and safety profile of the combination. Given the recent appreciation in Nektar’s market value and the amount of money Bristol has since paid to partner with them, it will be important to see this updated data hold the same promise as when it was initially presented for the first time last year.
Nektar will be webcasting an investor and analyst call to discuss ASCO data on Saturday, June 2nd at 6:45 PM CDT. More info about that can be found on the investor relations section of the company’s website.
ARMO Biosciences (Nasdaq: ARMO)
Overall survival of PEGylated pegilodecakin with 5-FU/LV and oxaliplatin (FOLFOX) in metastatic pancreatic adenocarcinoma (PDAC).
Responses and durability in NSCLC treated with pegilodecakin and anti-PD-1.
Pegilodecakin with nivolumab (nivo) or pembrolizumab (pembro) in patients (pts) with metastatic renal cell carcinoma (RCC).
Like Nektar’s NKTR-214, ARMO’s drug pegilodecakin is what is called a cytokine. NKTR-214 and pegilodecakin are a little different in that NKTR-214 is based on a cytokine called IL-2 and pegilodecakin is based on one called IL-10, but they are similar in that these cytokines are meant to be immune growth factors. In other words, they are designed to spark an increase in immune cells in and around tumors. This is a very hot area of cancer immunotherapy research currently. Not only did Nektar recently strike its large collaboration with Bristol-Myers Squibb, but it was also announced on May 10th that Eli Lilly and Company has agreed to acquire ARMO for $1.6 billion cash. At ASCO we will learn more about whether the clinical data behind it all matches the excitement.
ARMO’s most advanced program is trying to use pegilodecakin in combination with standard of care medicines in 2nd line metastatic pancreatic ductal adenocarcinoma (PDAC). In one ASCO presentation, the company will try to illustrate in early testing whether proliferating immune cells with pegilodecakin will boost the response rate of those standard medicines in PDAC. This will give us a hint at the likelihood of success of ARMO’s ongoing pivotal trial. There are also two other presentations that use pegilodecakin in combination with PD-1 checkpoint inhibitors for non-small cell lung cancer and renal cell carcinoma. Given that Nektar is testing NKTR-214 with Bristol’s nivolumab in those types of cancer as well, it will be interesting to compare and contrast these two combinations that harness cytokines.
Dynavax Technologies (Nasdaq: DVAX)
Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced melanoma who are naïve to anti-PD-1 therapy.
Dynavax’s cancer immunotherapy program centers around a cellular component called toll-like receptors that they believe can be stimulated to set off an immune response and kill tumors. The company’s lead drug, SD-101, stimulates the TLR9 toll-like receptor that is inside a type of immune cell called plasmacytoid dendritic cells (PDCs). These PDCs often are found in tumors, and the idea is that by stimulating TLR9, the cells will then create Interferon-α to attract a host of other immune cells to the area such as cytotoxic T-cells and kill the tumor. Just as Nektar and ARMO are trying to use cytokines to boost the efficacy of existing drugs like checkpoint inhibitors, Dynavax is trying to do the same with its TLR9 agonist.
Dynavax’s ASCO presentation will have some data showing the combination of the TLR9 agonist SD-101 with Merck’s checkpoint inhibitor pembrolizumab in patients with advanced melanoma who are naïve to anti-PD-1 therapy. Naïve means that the patients have not been previously given a PD-1 therapy such as pembrolizumab or nivolumab. The initial data from this presentation was released on May 16 by ASCO and there was some controversy about it. Dynavax announced a 60% overall response rate (15/25) for the combination, which would be a promising and positive number. However, it was also disclosed that 5 patients discontinued the study before they were evaluable. If you include them in the denominator, the overall response rate would then slip to a less impressive 50% (15/30). At ASCO we will see updated data from approximately 50 patients in total, which should provide a clearer picture as to what is the true response rate of this combination.
Merck (NYSE: MRK)
Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 1%: Open-label, phase 3 KEYNOTE-042 study.
Along with Bristol-Myers Squibb’s Opdivo, Merck’s PD-1 inhibitor Keytruda has become a standard of care for many types of cancers. Lately, the company’s success has been focused on non-small cell lung cancer. This type of lung cancer is sadly a leading cause of death due to smoking and better treatments are urgently needed. On an optimistic note, both Bristol and Merck have acheived successful trials leading to FDA approvals in second and third line advanced non-small cell lung cancer (second and third line means that patients have already been given other treatments that are no longer working), but it has only been Merck succeeding in newly diagnosed first line patients. This has been a huge commercial and scientific coup for them.
Merck’s first success in this first line advanced non-small cell lung cancer indication came in 2016 after the KEYNOTE-024 study showed that the drug was superior to chemotherapy for approximately 1/3 of patients whose tumors expressed the PD-L1 biomarker at 50% or greater. FDA ultimately approved Keytruda for that patient group and also later for use of in combination with chemotherapy for the other 2/3 of patients who don’t express PD-L1 as highly. Keytruda and chemotherapy together where shown to lower the likelihood of death by more than half in those less than 50% expressers. This is great news, but a goal of many in the immunotherapy community is to see if immunotherapy drugs like Keytruda can replace chemotherapy for more patients all together. That question brings us to ASCO.
Merck recently announced that a study called KEYNOTE-042 succeeded in its attempt to show that Keytruda could provide a superior outcome on its own over chemotherapy in patients whose tumors express the PD-L1 biomarker in as little at 1% or greater. This is great news and might in fact mean more patients will be eligible for immunotherapy alone. However, we have not seen the actual data and magnitude of the benefit yet. That is what Merck will be presenting at ASCO for the first time. And important thing to look for will be whether the success of the trial appears largely due to the very high expressers having excellent responses or if in fact many of the patients closer to the low 1% cutoff showed a clear benefit as well. If the latter is true, it might open the door to less lung cancer patients needing to start out on chemotherapy in the future. That would be a big win for patients and the field of immunotherapy.
Thanks, as always, for your interest in the field of immunotherapy and support of the Cancer Immunotherapy ETF.
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Opinions expressed are those of the author or Funds and are subject to change, are not intended to be a forecast of future events, a guarantee of future results, nor investment advice. Fund holdings and allocations are subject to change at any time and should not be considered a recommendation to buy or sell any security. Eli Lilly and Company is not a holding of the Fund or affiliated with the Fund.