Immuno-Oncology News brought you daily coverage of important discoveries, treatment developments, clinical trials, and other events related to cancer immunology throughout 2018.
We look forward to providing more news during 2019. As a reminder of what mattered most to you in 2018, here are the 10 most-read articles of last year.
The immunotherapy candidate pegilodecakin (AM0010), in combination with FOLFOXchemotherapy, was found safe for the treatment of advanced pancreatic cancer in the ongoing SEQUOIA Phase 3 trial (NCT02923921). The study is recruiting up to 566 participants whose tumors have progressed after first-line chemotherapy. It hopes to demonstrate that ARMO Biosciences‘s pegilodecakin plus chemo is better than chemo alone at extending patients’ lives. Updated results are expected by 2020, and if positive, may support the treatment’s approval in the U.S.
Another promising immunotherapy, called “switchable” CAR T-cell immunotherapy, was able to eliminate cancer in mice whose tumors came from cells of people with advanced pancreatic cancer, including cancer cells that had moved to distant organs. Unlike traditional CAR T-cell approaches, where immune cells target a specific region of a particular cancer protein, “switchable” CAR T-cells use adapter molecules (also known as antibody switches) that help them target multiple regions of a single protein, or even another cancer protein, if patients develop resistance. This also makes the treatment extremely safe, as researchers are able to stop the treatment if required.
A setback in the search for more effective therapies against melanoma was reported with the cessation of a Phase 3 clinical trial evaluating Keytruda (pembrolizumab) and epacadostat in metastatic melanoma patients. The KEYNOTE-252 (NCT02752074) trial failed to demonstrate that a combination of these two immunotherapies is better than Keytruda alone at stopping cancer progression, and a benefit in overall survival was not expected.
While the therapeutic potential of immune checkpoint inhibitors — a type of immunotherapy that restores the immune system’s ability to attack and destroy cancer cells — is increasingly recognized, the therapy comes with associated risks, such as the increased likelihood of the immune system attacking a patient’s own tissues. In an effort to help clinicians recognize the side effects early and deliver prompt treatment, the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) developed a set of guidelines regarding how to assess and manage the side effects associated with immune checkpoint inhibitors.
M7824, a treatment developed by EMD Serono for patients with advanced non-small cell lung cancer (NSCLC) who failed first-line chemotherapy, shrank tumors in 25% of patients in a Phase 1 trial (NCT02517398). The treatment has a dual mechanism, blocking the immune checkpoint molecule PD-L1 and trapping the immunosuppressive molecule TGF-beta. Aiming to enroll about 587 patients, the trial is recruiting at sites in the U.S., U.K, Canada, Australia, Europe, Korea, Taiwan, and Japan.
While the Keytruda-ecapadostat combination failed to improve the outcomes of metastatic melanoma patients, the immune checkpoint inhibitor alone showed promising clinical benefit among those with advanced hepatocellular carcinoma — the most common form of liver cancer. The ongoing KEYNOTE-224 Phase 2 trial (NCT02702414) tested Keytruda as a second-line treatment and showed that 16.3% of patients responded to treatment, and 61.5% had their disease stabilized. But only 1% of patients had their cancer eradicated.
Earlier last year, a new dosing scheduled of the immune checkpoint inhibitor Opdivo(nivolumab) was approved in the U.S. for several cancers, allowing it to be offered every four weeks. Opdivo was already approved as a 240 mg dose given every two weeks, but a 480 mg dose, given in a four-week schedule, was found comparable in terms of safety and efficacy. The approval also allows both regimens to be given in 30-minute infusions, cutting previous infusion time by half.
In addition to suppressing local immune responses by producing the PD-L1 immune checkpoint protein, cancer cells can also dampen systemic anti-tumor immunity through the release into the bloodstream of small vesicles armed with this molecule. While PD-1 inhibition with Keytruda reversed this effect in most patients, those with high blood levels of such vesicles had worse responses, possibly because of overly exhausted T-cells. The findings suggest that vesicle-associated PD-L1 in the blood could be used as a biomarker to identify patients most likely to respond to anti-PD-1/PD-L1 therapies.
2018 marked the first approval of an immunotherapy for metastatic small cell lung cancer (SCLC) patients who failed platinum-based chemotherapy and at least one other line of treatment. Bristol-Myers Squibb’s Opdivo became the first new medication for these patients in nearly 20 years after 12% of patients in a Phase 1/2 clinical trial responded to the treatment, regardless of their PD-L1 levels — a biomarker of response to Opdivo. Responses in CheckMate-032 (NCT01928394) lasted a median of 17.9 months, with some reaching up to 42 months. The accelerated approval is now contingent upon verification of clinical benefit in additional trials.
In a year where immunotherapy revealed such promise in lung cancer patients, our most-read story reported that Keytruda beats chemotherapy when given as a first-line treatment to NSCLC patients whose tumors are positive for the PD-L1 factor. The KEYNOTE-042 Phase 3 trial (NCT02220894) included patients with locally advanced or metastatic NSCLC and found that Keytruda significantly extended their lives compared to standard platinum-based chemotherapy. The treatment is being reviewed by the U.S. Food and Drug Administration and a decision is expected this month.
Immuno-Oncology News hopes that this news, along with our continuing reporting throughout 2019, will help educate, inform, and improve the lives of patients living with MS and their loved ones.
We wish all our readers a happy and inspiring 2019.