Grail validation data show highly accurate detection of cancers, tissues of origin

Grail validation data show highly accurate detection of cancers, tissues of origin

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A test in development for early detection of cancers was able to pick up a dozen of the deadliest cancer types at stages I-IV with a high degree of accuracy while also determining where the tumor was located, according to validation data announced Monday.

Menlo Park, California-based Grail said an analysis from its Circulating Cell-Free Genome Atlas, or CCGA study, showed that its early detection test could pick up more than 20 total cancer types with a low false-positive rate. Data from the analysis will be presented at the American Society of Clinical Oncology Breakthrough conference, which takes place in Bangkok from Friday through Sunday.

“Today, cancer remains the second leading cause of death worldwide, and we believe an effective multi-cancer early detection technology has the potential to transform the cancer care landscape,” Grail CEO Hans Bishop said in a statement.

The data set included 927 participants from the CCGA, including 654 who had cancer and 273 who did not, as well as 337 participants without cancer from the STRIVE study. The data showed a high degree of specificity, 99.3 percent, meaning there was a low false-positive rate. When looking at 12 deadly cancer types – anal, bladder, colorectal, esophageal, head and neck, liver/bile duct, lung, lymphoma, ovarian, pancreatic, plasma cell neoplasm and gastric – the detection rate was 76 percent, with a 99.3 percent specificity. Detection rates between stages I and IV were 39-92 percent. For those cancers, the tissue of origin – which helps to accurately identify where in the body a cancer originates – was provided for 97 percent and correctly identified in 93 percent of cases.

Among the more than 20 cancer types, the detection rate was 55 percent, ranging from 18-93 percent depending on stage and with the tissue of origin correctly identified in 93 percent of cases.

Minimizing false positive rates is a crucial aspect of the kind of early cancer detection system Grail is developing, with even seemingly small false positive rates making a significant difference for patients. When it reported data on 2,508 participants in its study at the ASCO annual meeting in June, Grail reported a 99 percent sensitivity rate – corresponding with a 1 percent false positive rate that the company had forecast was likely to go down.

While a false positive rate of 1 percent in a 5,000-patient population is manageable, an interviewed expert at ASCO said, it could become more problematic when the population reaches hundreds of thousands or millions. The danger of a high rate is that it could create problems for the cost effectiveness of early detection, as patients who got false positive results would have to be subjected to several tests afterward.

Source: Grail validation data show highly accurate detection of cancers, tissues of origin

Celgene invests $75M in cell therapy company Immatics as part of T-cell receptor partnership

Celgene invests $75M in cell therapy company Immatics as part of T-cell receptor partnership

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A large biotech company is pouring tens of millions of dollars into a German firm under a partnership to develop cell therapies in oncology.

Immatics Biotechnologies, based near Munich, said Wednesday that it had entered the partnership with Summit, New Jersey-based Celgene to develop T-cell receptor therapies, or TCRs, a type of cell therapy that differs in terms of structure and function from the more familiar CAR-Ts.

The deal includes a $75 million investment in the company by Celgene. Immatics would develop TCRs against solid tumor cancers using its in-house technology. It would be responsible for their development and validation through the lead candidate stage, at which point Celgene would have opt-in rights and assume responsibility for their global development, manufacturing and commercialization.

Both CAR-Ts and TCRs consist of T cells engineered to target proteins in cancer cells and are known in the field as adoptive T-cell therapies. However, whereas CAR-Ts recognize proteins on the surface of cancer cells, TCRs can recognize those inside them. A disadvantage to TCRs is that they are HLA-matched, meaning they can only be used in patients who harbor specific genetic profiles.

Two CAR-Ts are currently approved, both of which attack the cell-surface antigen CD19 in blood cancers: Novartis’ Kymriah (tisagenlecleucel) and Gilead Sciences’ Yescarta (axicabtagene ciloleucel). No TCRs have regulatory approval.

Immatics’ pipeline includes a variety of product candidates with different therapeutic modalities, including bispecific antibodies.

Celgene is already among the companies developing TCR therapies in solid tumors, through subsidiary Juno Therapeutics, which it acquired in January 2018 for $9 billion; Celgene itself is currently pending acquisition by Bristol-Myers Squibb, under a $74 billion deal announced in January of this year. Gilead is also developing TCRs, through the Kite Pharma subsidiary that originally developed Yescarta. A TCR Kite has in development is KITE-718, which targets the MAGE-A3/A6 pathway and is currently in a 75-patient Phase I clinical trial for tumors that carry the antigen. Adaptimmune is another company specializing in TCR therapies and currently has candidates in development that target MAGE-A4, MAGE-A10 and A2AFP in solid tumors.

Source: Celgene invests $75M in cell therapy company Immatics as part of T-cell receptor partnership

Roche drug is third to win biomarker-driven cancer approval from FDA

Roche drug is third to win biomarker-driven cancer approval from FDA

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Another drug designed to treat cancer patients based on a genetic driver rather than where tumors occur in the body has received approval from the Food and Drug Administration.

The FDA on Thursday granted Swiss drugmaker Roche’s Rozlytrek (entrectinib) approval for ROS1-positive non-small cell lung cancer and accelerated approval for solid tumors with NTRK gene fusions. The FDA approval follows an approval by Japanese regulators in June, based on results from the Phase II STARTRK-2 trial.

The drug is the second to receive a tumor-agnostic label for NTRK fusion-positive cancers since the November 2018 accelerated approval of Loxo Oncology – now part of Eli Lilly & Co. – and Bayer’s Vitrakvi (larotrectinib). And it is the third cancer drug to win a biomarker-based label overall, the first being Merck & Co.’s Keytruda (pembrolizumab), for microsatellite instability-high/mismatch repair-deficient cancers, in 2017.

The approval points to a growing view among the oncology community of cancers as genomic, rather than tissue-specific diseases. Meanwhile, the FDA has found that resistance is futile as the number of such biomarker-based drugs undergoing its review grows.

“Rozlytrek’s FDA approval for two rare types of cancer is an important advance for patients, combining a targeted medicine and genomic testing to bring this new treatment option to patients who are waiting,” said Sandra Horning, chief medical officer at Roche’s Genentech division, in a statement. “Rozlytrek is the first FDA-approved treatment that selectively targets both ROS1 and NTRK fusions and, importantly, has also shown responses in these rare cancer types that have spread to the brain.”

In addition to Rozlytrek having the additional approval for ROS1-positive NSCLC, another difference with Vitrakvi is that its accelerated approval for NTRK fusion cancers is narrower in terms of the age range for which it’s approved. Whereas Vitrakvi was approved for pediatric and adult patients, Rozlytrek’s NTRK fusion label is for adolescents and adults, aged 12 and older.

NTRK fusions are rare generally, but their prevalence can vary considerably between cancers, from 1 percent or less in some solid tumors among adults to more than 90 percent in infantile fibrosarcoma, which affects infants and young children.

While not commenting specifically on Rozlytrek, Seattle Children’s Hospital oncologist Dr. Douglas Hawkins said in an interview at the American Society of Clinical Oncology in June that whereas one can often guess whether a pediatric tumor carries an NTRK fusion based on what kind of tumor it is, the reverse is true among adults. Among children, NTRK fusions may even occur where they would not be expected, such as in pediatric leukemias.

“You can identify the bulk of tumors having NTRK fusions based on what the tumor looks like,” Hawkins said. “In adults, it’s the complete opposite.”

Indeed, when Vitrakvi was approved, a medical oncologist commented that finding NTRK fusions in adults was like finding a needle in a haystack.

NTRK’s role as a genetic driver of tumors in which it occurs nevertheless means that a specific inhibitor of it – such as Vitrakvi or Rozlytrek – has a high probability of inducing a response. In the four clinical trials of 54 patients with NTRK fusion-positive cancers that led to the accelerated approval, 57 percent of patients experienced a partial or complete response, with complete responses occurring among 7.4 percent.

Among 51 NSCLC patients with ROS1 mutations, the response rate was 78 percent, with 5.9 percent of patients’ tumors disappearing entirely. Among the NTRK fusion patients, 61 percent showed durations of response lasting nine months or longer, while 55 percent of responders with ROS1 mutations maintained their responses for 12 months or longer.

Source: Roche drug is third to win biomarker-driven cancer approval from FDA

Kite Pharma founder’s venture capital firm closes new $600M fund

Kite Pharma founder’s venture capital firm closes new $600M fund

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A venture capital firm formed by a founder of one of the first companies to win Food and Drug Administration approval for a cell therapy for cancer closed a new fund worth more than half of $1 billion.

Boston-based Vida Ventures said Thursday that it had closed its Vida Ventures II, or Vida II fund, raising $600 million. The close brings the total amount the firm has raised to about $1 billion since the firm’s founding in late 2017 by Arie Belldegrun, founder of Kite Pharma. Kite won FDA approval for Yescarta (axicabtagene ciloleucel) in diffuse large B-cell lymphoma in October 2017. In August of that year, Gilead Sciences announced it would acquire Kite for $11.9 billion.

A Form D filed with the Securities and Exchange Commission on July 15 states that the firm had sought to raise $600 million. Another Form D, filed Dec. 6, 2017, states that Vida had raised $254.8 million.

“Vida maintains a unique advantage by combining a best-in-class investment team with firsthand business and scientific expertise that directly applies to our portfolio investments,” Belldegrun said in a statement. “With the added expertise from our newest team members, we are positioned better than ever before to add value by identifying and investing in meaningful science that ultimately has the potential to help patients in need.”

In its most recent publicly announced investment, Vida co-led a $105 million Series A funding round for Kronos Bio, along with Omega Funds. The San Mateo, California-headquartered company is developing small-molecule drugs to target historically undruggable targets.

Last year, Belldegrun and fellow Kite alumnus David Chang founded Allogene, a South San Francisco, California-based company developing “off-the-shelf” allogeneic CAR-T therapies, which use T cells from donors rather than requiring the harvesting of patients’ own T cells. The company raised a $120 million private financing in September of last year before filing to go public the same month.

Source: Kite Pharma founder’s venture capital firm closes new $600M fund

Exact Sciences buys fellow oncology diagnostics company Genomic Health for $2.8B

Exact Sciences buys fellow oncology diagnostics company Genomic Health for $2.8B

Madison, Wisconsin-based diagnostics company Exact Sciences has agreed to purchase Genomic Health in a $2.8 billion cash-and-stock deal to create a powerhouse in the oncology diagnostics industry.

Exact Sciences, known for their Cologuard colorectal cancer screening test, has continued to branch out into different cancer indications through internal pipeline development and now through M&A.

Colorguard is an at-home stool-based DNA test that was developed in conjunction with the Mayo Clinic and initially launched in 2014. In the five years since, the diagnostic has been used on more than 2.6 million people and has helped uncover 12,000 cases of early-stage cancer and 84,000 pre-cancerous polyps.

Exact’s combination with Redwood City, California-based Genomic Health adds the company’s Oncotype DX Breast flagship genomic test for early-stage breast cancer to its product portfolio.

Oncotype DX Breast is a genomics-based diagnostic that is used to help clinicians understand the risk of cancer recurrence and the effectiveness of certain therapies on their disease. Outside of the company’s primary breast cancer product, Genomic Health also has diagnostics targeting prostate and colon cancer in its portfolio.

The companies tout the deal as expanding Exact’s commercial footprint to 90 countries and creating a leader in the cancer diagnostic space with projected 2020 revenues of $1.6 billion.

Alongside the news of the merger, both Exact Sciences and Genomic Health announced their second quarter financial results.

In the second quarter, Exact Sciences earned revenues of $2oo million, equivalent to roughly 94 percent growth year-over-year. Genomic Health’s revenue in Q2 2019 was $114.1 million, an increase of 19.4 percent from 2018.

“When we think about the complementary strengths of our organization, doing it with a record quarter coming from Genomic Health and the optimism we have going forward this is the right time for a deal,” Genomic Health CEO Kim Popovits said on an investor call. “We really believe we have a one plus one equals three scenario.”

Exact Sciences executives say that bringing in Genomic Health’s expertise and financial resources will allow the company to invest in products to identify and test for property biomarkers in other common cancer types.

“Long term bringing together Exact Sciences and Genomic Health will create an organization with a breadth of capabilities that doesn’t exist today,” Exact Sciences CEO Kevin Conroy said on the call, estimating a $200 million R&D budget for the combined company.

“At its core this combination is about bringing together two complementary capabilities to create a leading cancer diagnostics company with unique abilities to impact more people’s lives.”

One specific program that executives said would benefit from the Genomic Health combination is Exact’s early-stage screening for hepatocellular carcinoma, the most common type of liver cancer. Conroy said Genomic Health’s existing commercial infrastructure for international sales gives the company a ready-made avenue to expand sales outside of the U.S.

Another recent area of development for Exact Sciences has been the development of liquid biopsy products, particularly for the early-stage screening of lung cancers to avoid unnecessary biopsy. Adding Genomic Health’s laboratory presence in California bolsters the company’s the reimbursement strategy for the emerging technology.

Genomic Health has also been working on its own liquid biopsy-based products and said merger could accelerate that development, particularly with the company’s predictive test for late-stage breast cancer recurrence.

Exact Sciences purchase price represents around a 19 percent premium on Genomic Health’s weighted average stock price over the last month.

The deal is expected to be closed by the end of the year pending regulatory and shareholder approval of the deal. The board of directors of the companies have both unanimously approved the deal.

Photo: Kritchanut, Getty Images

Source: Exact Sciences buys fellow oncology diagnostics company Genomic Health for $2.8B

Nanotech injection nabs cancer cells on the run

Nanotech injection nabs cancer cells on the run

Cellular soldiers created using the body’s own defenses can track down and kill cancer cells that escape during surgeries, researchers report.

This could prevent metastasis and save lives, particularly in cases of triple-negative breast cancer.

Researchers attached two proteins to the surface of lipid nanoparticles: TNF-related apoptosis-inducing ligand—or TRAIL—and the adhesion receptor E-selectin. The injected nanoparticles then adhere to white blood cells, and the introduction of these TRAIL-coated leukocytes into the bloodstream before, during, and after tumor removal kills all cancer cells loosed as a result.

“Collisions between the TRAIL-coated leukocytes and cancer cells in the bloodstream are happening constantly,” says Michael King, a professor of engineering and chair of the biomedical engineering department at Vanderbilt University.

“We’ve tested this both in the bloodstream and in hundreds of blood samples from cancer patients being treated in clinics across the country. In all cases, within two hours, the viable cancer cells are cleared out. This has worked with breast, prostate, ovarian, colorectal, and lung cancer cells.”

Not only can the method work during surgeries, King says, but also potentially with patients who already suffer metastatic cancer in multiple sites and who have no worthwhile treatment options. Because all the components of the TRAIL-coated leukocytes occur naturally in the body, it increases the potential for a quicker path from the bloodstreams of mouse models to human trials.

Surgical intervention in breast cancer is a known cause of metastatic growth and accelerated tumor relapse, either because of cancer cells shed during the process, inflammation at the wound site, or a combination of the two factors. Chemotherapy is the most widely used treatment for the resulting metastasis, but still, the five-year survival rate for triple negative breast cancer sits well below 30%.

The group’s past experiments with TRAIL-coated leukocytes were effective in blocking metastasis, but required multiple repeated injections to sustain their beneficial effect. King says this new breakthrough overcomes those issues by designing three simple doses to coincide with the surgical procedure.

The paper appears in Science Advances. Support for the work came from the National Institute of Health and the NCI/NIH Cancer Center.

Source: Vanderbilt University

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Source: Nanotech injection nabs cancer cells on the run