Cancer therapy is going through a true revolution. Thanks to different forms of immunotherapy, patients with cancers that were previously untreatable now show stunning survival rates. The efficiency and patient population treatable further increases when different immune-oncology strategies are combined. But tweaking immune cells into targeted action is a tricky occupation, and some immunotherapies have notorious side effects.
An excerpt from the BioVox White paper on Cancer Immunotherapy.
Established cancer therapies lead to a prolongation of survival, but most often there is no cure. Exceptions include surgery that is performed before the cancer has spread, but cures are rare and limited to certain cancer types. With the advent of immunotherapy, the potential exists for treatment of cancers that were previously considered untreatable, significantly prolonging life. There is hope that this could transform old-fashioned chemotherapy agents from first line treatments to a last resort, considering their efficiency and side effect profile.
Research into how the immune system can be leveraged to fight cancer has been ongoing for decades. The field began drawing mainstream attention after the discovery of checkpoint inhibitors, which are now seen as the poster children of the area. The antibodies directed against the cancer proteins putting a break on the immune system showed most impressive results, attracting more investigators towards the topic. Now that the first of these agents are on the market, the goal remains to make them a first line of treatment. A first step in reversing the order of therapy has already been taken, with the first line approval for checkpoint inhibitors in lung cancer.
The most remarkable results were obtained in melanoma, with the checkpoint inhibitors ipilimumab (a CTLA-4 inhibitor), and pembrolizumab and nivolumab (PD-1 inhibitors). For example, a treatment with ipilimumab could achieve a complete response in 15 – 20% of melanoma patients. Terminally ill patients that received this therapy were in sustained remission afterward. These patients, who would normally have had only months to live, are currently alive after 10 years. While discussing a cure for cancer was always farfetched, these results have proven that it may be well within reach.
Combination therapy is the next big thing
There is a consensus in the field that combinations of different immunotherapies will be the optimal way to treat patients, as they often show synergistic effects. For example, the combination of ipilimumab with nivolumab could increase the response rate in melanoma patients from 15 – 20% to the 40 – 50% range, a dramatic improvement. Similarly, promising results were obtained by combining mRNA-based immune activating therapies and checkpoints.
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Because of the potency of combination therapies, you’re no longer the main decider in immunotherapeutic development.
This understanding that combinations of immunotherapies work synergistically drastically impacts the way companies develop their products. Traditionally, a product was developed and approved, and combinations were tested afterward. Now, the partners have to be picked earlier on in the process, which is inherently more risky and also challenging in terms of partnering, value creation towards investors, pricing, reimbursement, and, last but not least, IP.
“In immunotherapeutic development, you’re no longer the main decider because combinations will be very powerful,” explains Gregory Driessens, Head of In Vivo Pharmacology at iTeos. “You can have a very good product, but for the optimal combination, you will be dependent on a partner. That makes the equation a bit more complicated compared to a monotherapy treatment where you can decide your entire marketing strategy by yourself.”
Taking the bad with the good
While immunotherapies have shown astounding effects, activating the immune system more strongly is not without risk; in some of the early trials, 1% of the patients died because their immune system derailed. Luckily, improved knowledge on how to use these agents has diminished the risk of severe side effects. However, the acceptable risk-benefit ratio for cancer treatments is an additional ethical factor that has to be included in the equation for new innovative therapies. Historically, established methods, such as surgery or chemotherapy, have faced these considerations as well.
“Treatment-related toxicity is an issue for all early phase clinical trials, and immuno-oncology is no exception,” clarifies David Gilham, Vice President of R&D at Celyad. “However, the risk-bene t balance is always considered — thus, while there are well-publicized toxicity issues in the CD19 CAR T cell therapy, the staggering clinical response rate in patients with advanced treatment resistance to the disease are driving the therapy forward. Clearly, more research is ongoing to identify the root causes of such toxicity and further improve safety pro les, but the clinical responses in these therapies are raising challenges in clinical trial design to support the desire of patients to bring such effective therapies into the market as soon as possible.”
This piece is an excerpt from the BioVox White paper on Immunotherapy. Get your full copy here.
