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AACR 2019 Roundup: Notes from a Weekend of Early Stage Cancer Results

Xconomy National — 

[Editor’s note: Alex Lash co-authored this report] The American Association for Cancer Research’s annual meeting is wrapping up in Atlanta today. The conference typically focuses on early research and clinical work, not the big trials that can change the way doctors practice medicine and that compete for headline space at conferences like the American Society for Clinical Oncology.

But AACR has its fair share of notable news, events, and reports. In case you missed the flow of stories that started last weekend—or you just want to refresh your memory—we’ve rounded up some of the highlights here and put them in the context you need to know if you’re not an expert.


Lung cancer is the leading cause of cancer death in the U.S. Immunotherapy is starting to make a difference, shifting from last-ditch medicines to first options and helping patients with advanced lung cancer live longer.

At AACR, a pooled analysis from four studies of Bristol-Myers Squibb’s (NYSE: BMY) immunotherapy nivolumab (Opdivo) showed that 14 percent of advanced non-small cell lung cancer patients who got the drug after failing others are alive after four years. Before the age of immunotherapy, the typical five-year life expectancy for these patients was 10 percent, or less than 1 percent for those whose cancer had spread widely, according to an American Cancer Society study of patients between 1999 and 2010.

A regimen combining Merck’s (NYSE: MRK) pembrolizumab (Keytruda) with chemotherapy has become the standard of care for many patients with newly diagnosed, advanced NCLSC, which is the most common form of lung cancer. Data at AACR showed the pembro-chemo impact on NSCLC that has spread to the liver or brain, a tough situation to treat.

For those with small cell lung cancer, a fast-moving form of the disease often linked to smoking, the standard of care for decades has been chemo. Immunotherapy is now here. Nivolumab was approved last August for patients who had failed two treatments, though some recent stumbles have put that approval in peril. And the FDA in March okayed the combination of Roche’s atezolizumab (Tecentriq) and chemotherapy for newly diagnosed advanced SCLC.

Merck wants to join the fray, and at AACR, a pooled analysis of two pembrolizumab (Keytruda) studies examined the drug’s benefit in those who haven’t responded to multiple treatments, as Fierce Pharma reports here. Merck is hoping for a mid-June approval.

Down the road, two immunotherapy-chemo combinations from Merck and AstraZeneca (NYSE: AZN) in first-line SCLC patients are both in Phase 3 testing and could threaten Roche’s lead. Both should produce data by the end of the year.

Immunotherapy isn’t an option for the minority of lung cancer patients whose tumors are driven by genetic alterations such as ALK and EGFR. These patients instead get drugs like osimertinib (Tagrisso) and crizotinib (Xalkori), which target tumors with those signatures. But tumors develop resistance to targeted drugs, creating an opening for medicines that can pick up the slack.

China’s Chi-Med (NASDAQ: HCM), with AstraZeneca, is pursuing one such drug called savolitnib. At AACR, savolitinib showed encouraging results in an early stage study in lung cancer patients who had failed osimertinib. Chi-Med isn’t alone here: similar, rival drugs capmatinib (from Novartis and Incyte) and tepotinib (Merck KGaA) are in the mix as well.


Despite the advances in other cancers, pancreatic cancer remains an intractable foe. It’s hard to detect, moves fast, and can’t be surgically removed. The disease was the third-leading cause of cancer-related death last year and will kill an estimated 45,750 Americans in 2019, according to the American Cancer Society.

There is progress on two fronts. The first is with a group of drugs which block poly ADP ribose polymerase (PARP), an enzyme cancer cells use to repair themselves. PARP blockers have been approved for breast and ovarian cancers. And one, olaparib (Lynparza), could soon break through in pancreatic cancer, although its owner AstraZeneca has yet to divulge key details from its Phase 3 study.

GlaxoSmithKline (NYSE: GSK) has a rival drug, via its buyout of Tesaro, being tested in pancreatic cancer. And at AACR, University of Pennsylvania investigators presented a Phase 2 study of another PARP inhibitor, rucaparib (Rubraca) from Clovis Oncology (NASDAQ: CLVS). As with olaparib, rucaparib was used as a maintenance therapy, to keep pancreatic cancer in remission after chemotherapy treatment. Rucaparib was tested in patients whose tumors have either a mutated BRCA or PALB2 gene, some 6 to 8 percent of those with pancreatic cancer; Olaparib was studied only in BRCA-positive patients.

Upon an interim look at the rucaparib study, 19 evaluable patients had their cancers held in check for a median of 9.1 months after starting treatment. One of those patients had no trace of cancer, while six others saw their tumors partially shrink. The most common side effects—like nausea, vomiting, diarrhea, fatigue—weren’t considered serious. Clovis is “evaluating a potential clinical and regulatory path forward” for rucaparib in pancreatic cancer and should have an update later this year, CEO Patrick Mahaffy said in a statement.

Elsewhere, an immunotherapy combination showed positive, albeit early promise. The Parker Institute for Cancer Immunotherapy—which Napster founder Sean Parker formed with a $250 million investment in 2016—posted results from a Phase 1 study testing a combination of chemotherapy, nivolumab, and the antibody APX005M, from privately held Apexigen, which is meant to boost responses to immunotherapy.).  The early results—54 percent of the 24 evaluable patients responded—have greenlighted a Phase 2 study. Here’s more from STAT.


The first U.S. approval of an immunotherapy for breast cancer came last month. The nod went to a combination of Roche’s immunotherapy atezolizumab and the chemotherapy nab-paclitaxel (Abraxane), owned by Celgene (NASDAQ: CELG), to treat triple-negative breast cancer (TNBC), an aggressive form of the disease that makes up 15 percent of all breast cancer cases.

More immunotherapy combinations for TNBC are in the pipeline. Roche presented early results at AACR from a Phase 1b study of a three-drug cocktail that includes atezolizumab, Abraxane, and Roche’s ipatasertib. The interim data showed 19 of 26 patients (73 percent) responding to the treatment. But more than half suffered serious adverse events, the most common being diarrhea and rash.

A different type of immunotherapy also showed promising signs, albeit extremely early. In a sample of nine patients, five saw their TNBC tumors disappear after treatment with the cancer-killing virus product talimogene laherparepvec (T-Vec), from Amgen (NASDAQ: AMGN), and chemotherapy. The other four saw tumors shrink but not disappear. Two patients suffered serious side effects.

A long-term study from the American Cancer Society showed that prostate cancer is on the wane in a few countries around the world—most notably the U.S.—and not growing in frequency in many others. Prostate cancer incidence was examined for 44 countries. The study also looked at the mortality rate for 71 countries. Fourteen countries showed a decrease, three an increase, and in 54 countries the rate remained stable.


—CAR-T cell therapy, which uses a modified form of a patient’s own live immune cells, has come to market for certain types of leukemia and lymphoma. But making CAR-T work in the more common solid tumors—breast, lung, colon, and the like—requires a lot more work because of those tumors’ ability to fight back against the immune system and bounce back if they’re not totally eradicated. Any promising signals for CAR-T in solid tumors are notable. At AACR, a Phase 1 study from Baylor College of Medicine looked at 10 patients with sarcomas—rare cancers that grow in the connective tissue. Two had complete responses to an experimental CAR-T treatment that targets cells expressing the HER2 protein. Three saw their cancers kept in check, and five did not see any benefit.

Another study at Memorial Sloan Kettering Cancer Center gathered 21 patients with mesothelioma, a cancer of the lung lining, and gave them a CAR-T treatment designed to seek out cells expressing the protein mesothelin. Two had a complete response, five had a partial response, and four saw their cancers kept in check.


Guardant Health (NASDAQ: GH) is one of several companies with a blood test to help doctors prescribe drugs based on the genetic profile of a patient’s diagnosed tumor. Data at AACR showed that the test, called Guardant360, could be an alternative to tissue-based biopsy for newly diagnosed lung cancer.

Also at AACR, a smaller firm called Resolution Bio presented data that its test uncovered more “actionable” information about patient’s lung tumors than Guardant360.

So-called liquid biopsies, which genetically profile a patient’s cancer or flag its return after remission, are becoming more established by the day.  While access to the tests and understanding their results has caused concern, Medicare has begun covering their costs.

Developers like Guardant are also aiming for a bigger target: Screening tests that find cancer before a person develops symptoms. As does its well-funded rival Grail, Guardant wants eventually to deliver a screening product that only requires a blood draw. It is following a cautious roadmap, as Xconomy described when Guardant’s effort, dubbed Lunar, was unveiled three years ago.

Only recently, Guardant made Lunar available to drug companies and researchers. It’s not close to being an on-the-ground diagnostic tool. Guardant first wants to show that Lunar can characterize previously diagnosed tumors. It took a first step in that direction with a small study in colon cancer unveiled at AACR. It’s extremely early days, as Vantage pointed out. Of the 105 patients in the study, only 25 had early-stage cancer. It is those patients, ultimately, that Guardant and its rivals want to detect. The earlier a tumor is treated, the more successful the treatment could be. The trick will be to make cancer screening as accurate as possible, because screens that give false results can do far more harm than good.