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Focus Feature on Cancer Research: Combating cancer with creativity
December 2018
by Kelsey Kaustinen  |  Email the author
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The more we learn about cancer, the easier it is to see why the disease continues to stymie drug developers. From hijacking the vascular system to feed tumors and camouflaging itself from immune checkpoints, to evolving to develop resistance to previously effective drugs, cancer has dozens of ways to evade treatment.
 
But researchers are proving just as inventive in finding new ways to target the disease, not just by blocking off how it spreads, but also by researching how to get around each new shield cancer puts in place. This year has been a productive one in terms of discovering new ways to target cancer, and as 2018 winds to a close, we’ve selected some of the most recent—and most cutting-edge—ways that the industry has found to come at cancer sideways.
 
Bacteria and toxicity
Off-target effects are a stumbling block for any kind of drug, but for cancer, where drugs must be strong enough to kill off resilient cells that are designed to survive and spread, unintended toxicity is a particular issue. The industry has been working to address this issue by using more tightly targeted therapeutics or combination approaches that allow for lower (and less toxic) doses, but The Scripps Research Institute is looking back to the start, to the very origin of such drugs.
 
The question TSRI explored in recent work was the mechanism by which the compounds that are engineered into natural product-based drugs are kept safe from their own toxicity.
 
The answer they discovered is tied to a class of natural products known as enediynes, which are yielded by bacteria referred to as actinomycetes, which are found in soil. Two cancer drugs based on enediynes have been approved, but treatment resistance is a common problem for these compounds.
 
The lab of Dr. Ben Shen, professor, co-chair of the Scripps Research Department of Chemistry and senior author on this latest work, has been focused on the exploration of enediynes. Two mechanisms by which bacteria can protect themselves from enediynes have previously been discovered, and in a recent Cell Chemical Biology study, Shen and his lab shared news of a third, which hinges on three genes: tnmS1, tnmS2 and tnmS3.
 
These genes encode proteins that enable bacteria to resist a subset of enediynes known as tiancimycins, which are being explored as a base for new cancer drugs.
 
Those proteins bind to tiancimycins, isolating them from the rest of the organism, according to a TSRI press release. Shen and his team also identified the three tnmS genes in microorganisms present in the human microbiome.
 
Shen noted that this implies that microbes in the gut could then pass these proteins on to their human hosts, thereby conferring drug resistance.
 
“These findings raise the possibility that the human microbiota might impact the efficacy of enediyne-based drugs and should be taken into consideration when developing new chemotherapies,” he added. “Future efforts to survey the human microbiome for resistance elements should be an important part of natural product-based drug discovery programs.”
 
A different kind of delivery
Scripps isn’t the only organization looking into the potential of bacteria. Swiss biotech T3 Pharmaceuticals received the “2018 Science Start-Up of the Year” award from Falling Walls Venture in the fourth quarter of the year for such work.
 
T3’s approach harnesses engineered bacteria to trigger the immune system “by delivering selected human proteins directly into cells of the tumor microenvironment,” the company explains. As noted in a Journal of Cell Biology article, “Bacteria have developed sophisticated nanomachines enabling the delivery of virulence proteins into eukaryotic cells (translocation). The type III secretion (T3S) system of certain gram-negative bacteria functions like a nanosyringe that injects substrate proteins into target cells.”
 
T3 notes that their approach is much faster than the current standard of DNA transfection, which “results in a heterogeneous and unsynchronized cell population after an incubation time of 12 to 48 hours. Hence, the protein under study is often present for far longer than physiologically relevant or desirable.” By harnessing the natural mechanisms of these bacteria, the company claims that they can offer “a fast, synchronized, homogenous and efficient protein delivery into almost all available cell lines.”
 
Putting T cells to work
Pairing drugs with antibodies to better direct them to tumors is a familiar concept, as seen by the rapid growth of the antibody-drug conjugate market. And recent work out of the Massachusetts Institute of Technology (MIT) is echoing that concept of effective pairings, but with a twist—rather than attaching drug payloads to antibodies, a research team has found a way to attach drugs to T cells.
 
T cells, lymphocytes that play a major role in the immune system’s response to cancer or infections, are one of the key cell types researchers are working to harness in better targeting cancer. By re-equipping the immune system to bypass cancer’s defenses, rather than trying to overpower it with higher doses of drugs, cancer treatment is more targeted and has fewer side effects.
 
Adoptive T cell therapy has emerged as a way to harness the immune system against tumors. Tumor-specific T cells are taken from a tumor, grown and expanded, then returned to the patient, or else circulating T cells are taken from the blood, modified to target proteins expressed on the surface of tumors, and then reintroduced to the patient’s system.
 
Dr. Darrell Irvine’s lab has been working on this approach for years, having reported a method in 2010 for attaching liposomes with cytokine payloads to tumor-specific T cells. There were drawbacks, however, in the form of a hard limit on how much of a payload the cytokines could carry, and their tendency to release the drug as soon as they were injected, rather than when they reached the tumor.
 
This year, the team debuted a new approach, which was published in Nature Biotechnology. Irvine and his colleagues developed a new nanoparticle that can hold 100-fold more of a drug payload and does not release it until the T cells reach the tumor. Comprised of a gel engineered from IL-15 molecules, the nanoparticle is bound by a cross-linker that does not degrade until activated by a chemical change triggered by its T cell vehicle reaches a tumor and activates, as noted in a press release by MIT’s Anne Trafton.
 
“We found you could greatly improve the efficacy of the T cell therapy with backpacked drugs that help the donor T cells survive and function more effectively. Even more importantly, we achieved that without any of the toxicity that you see with systemic injection of the drugs,” said Irvine, a professor of biological engineering and of materials science and engineering, a member of MIT’s Koch Institute for Integrative Cancer Research, and senior author of the Nature Biotechnology study.
 
When tested in mouse models with T cells designed to express a T cell receptor targeting a protein common in melanoma tumors, the tumors disappeared in roughly 60 percent of the mice. Similar effectiveness was seen in models with engineered glioblastoma cells. In addition, with the IL-15 linked to the gel nanoparticles, they were able to administer eight times as much of the therapeutic without side effects.
 
The clinical trials for this approach are being performed by Torque Biotherapeutics, of which Irvine is a co-founder. In a recent press release detailing the presentation of preclinical data at this year’s AACR meeting, Dr. Thomas Andresen, chief scientific officer of Torque, reported that “Both Il-15 and IL-12 are potent cytokines capable of inducing strong antitumor immune responses, yet their clinical use as systemic therapies is limited by the potential for severe toxicities. Anchoring these powerful immune activators to the surface of T cells that traffic to tumors is a unique approach to direct immune power in the tumor microenvironment. These preclinical studies demonstrate superior efficacy for this approach compared to systemic administration of these same cytokines and are the foundation for the first clinical trials that will begin later this year for Deep IL-15.”
 
From HIV to breast cancer
Also in November, CytoDyn Inc. filed an Investigational New Drug application with the FDA for a Phase 1b/2 clinical trial of PRO 140 (leronlimab) in patients with metastatic triple-negative breast cancer. PRO 140 is a CCR5 antagonist being investigated by CytoDyn in HIV infection, given its connection with CCR5. By masking CCR5, HIV (R5) subtype is barred from entering and infecting healthy T cells.
 
However, CCR5 plays a part in tumor metastasis and immune signaling as well, and works to direct the flow of immune cells to inflamed sites. In terms of cancer, increased expression of CCR5 is a warning sign for several cancers, as it supports tumor invasion and metastasis, and CCR5 inhibitors have proven capable of blocking metastases in lab and animal models of breast and prostate cancer. Given that, CytoDyn is further exploring PRO 140 in cancer as well as HIV, with the intent of launching clinical trials in metastatic triple-negative breast cancer this year.
 
According to Dr. Richard Pestell, CytoDyn’s interim chief medical officer, “My previous study of 2,200 patients showed that more than 50 percent of all breast cancer overexpress CCR5, and more than 90 percent of patients with triple-negative breast cancer re-expressed CCR5 selectively on their cancer. PRO 140, which has been shown as very safe without any reported drug-related serious adverse events in more than 620 patients, binds avidly to CCR5 on human breast cancers. Together, these findings suggest PRO 140 may be both a highly selective and safe therapeutic for patients with metastatic breast cancer. The ability to demonstrate efficacy in this patient population could serve as proof of concept of PRO 140’s potential to have a positive effect in other types of metastatic cancers. We look forward to detailing the protocol for this trial following the FDA review period.”
 
A new ‘buzz’ in glioblastoma
One of the most unusual approaches in this collection of news is based on bees. Moleculin Biotech Inc. recently launched a Phase 1 clinical trial of WP1066 in glioblastoma. The small-molecule drug candidate is derived from the active ingredient in propolis, which is produced by honey bees.
 
WP1066 inhibits STAT3, a cell signaling protein that plays a role in cell growth and proliferation, tumor angiogenesis, tumor development and immune response triggering. STAT3 also helps tumors cells to evade the immune system and metastasize to secondary locations.
 
“Treating the first brain tumor patient with WP1066 is the start of a very exciting and encouraging program for doctors treating the worst types of brain cancers. There has been very little progress in recent years toward improved therapies for glioblastoma and other aggressive primary or metastatic brain tumors. WP1066 has shown extremely promising results based on animal studies where we have seen inhibition of tumor growth and improvements in survival,” said Dr. Sandra Silberman, a world-renowned oncologist and Moleculin’s chief medical officer. “This is based on the fact that although STAT3 has long been identified as an important target for treating tumors, for years most efforts have focused on attempts to indirectly inhibit STAT3 from upstream signaling, not from within the cancer cell itself. WP1066 appears to be unique in its ability in vitro and in animal models to consistently and directly inhibit the activated form of STAT3 and produce significant anticancer effects, including tumor growth inhibition and increased life span of treated animals.”
 

Interim data supports combination therapy in multiple cancer types
 
TOKYO—This year’s annual meeting for the Society for Immunotherapy of Cancer saw Eisai Co. Ltd. and Merck & Co. Inc., known as MSD outside of the United States and Canada, share data regarding a combination regimen of Eisai’s Lenvima (lenvatinib) and Merck’s Keytruda (pembrolizumab). The combination therapy was tested in three types of metastatic cancer, including non-small cell lung cancer (NSCLC), melanoma and urothelial carcinoma.
 
Though the companies presented only interim analysis data, the two therapies were generally well tolerated in all three indications. In addition, they saw “encouraging antitumor activity,” according to a company press release.
 
In a Phase 1b/2 trial of Lenvima and Keytruda in patients with metastatic NSCLC, the primary endpoint—objective response rate at week 24 per immune-related RECIST (irRECIST)—was 33.3 percent. Median progression-free survival per irRECIST was 5.9 months, with a progression-free survival rate at 12 months per irRECIST of 29 percent. The median duration of response (DOR) was 10.9 months.
 
Though the combination therapy was generally well tolerated, there were some adverse events. Ten patients (48 percent) in the NSCLC cohort saw Grade 3 treatment-related adverse events (TRAEs), with one patient (5 percent) experiencing Grade 4 TRAEs and one treatment-related death. The most common adverse events of any grade were decreased appetite, proteinuria, hypertension, fatigue, hypothyroidism, diarrhea and arthralgia. These TRAEs were common in the other two combination cohorts as well, with the melanoma cohort also seeing cases of dysphonia. In addition, the entirety of the melanoma arm experienced at least one TRAE, though there were no treatment-related deaths.
 
In the patients with metastatic melanoma, researchers saw an objective response rate (ORR) at week 24 per irRECIST of 47.6 percent, with median PFS of 5.5 months and a PFS rate at 12 months of 34.7 percent. Median DOR was recorded as 12.5 months.
 
The urothelial carcinoma arm featured 20 individuals who were either treatment-naive or who had received up to two prior lines of therapy. In terms of the primary endpoint, ORR at week 24 per irRECIST in this cohort was 25 percent. In terms of secondary endpoints, the interim results reported median PFS of 5.4 months. Like the NSCLC cohort, this arm of the trial also saw one treatment-related death.
 
“We are increasingly confident that these interim analyses of new clinical trial data on the combination of Lenvima and Keytruda in non-small cell lung cancer, melanoma and urothelial cancer continue to verify the potential of this combination,” Dr. Takashi Owa, vice president and chief medicine creation officer, Oncology Business Group at Eisai, stated in a press release. “Through our collaboration with Merck & Co. ... we are doing our utmost to be able to provide this combination to patients in need of new treatment options as soon as possible.”
 
These studies fall under an agreement established by Eisai and Merck & Co. in March to co-develop and co-commercialize Lenvima as both a monotherapy and in combination with Keytruda. Beyond the studies that are already underway, the partners will also conduct clinical studies investigating the combination regimen of Lenvima and Keytruda in 11 potential indications covering six types of cancer—bladder cancer, endometrial cancer, head and neck cancer, hepatocellular carcinoma, melanoma and NSCLC—as well as a basket trial featuring six other subtypes of cancer.
 

A new neutropenia option for chemotherapy patients
 
NEW YORK—Despite increasing efforts to minimize the off-target damage of cancer treatments, most drugs come with side effects. One of the more common issues, particularly with chemotherapy, is neutropenia, when an individual’s counts of neutrophils (white blood cells) are drastically low. The condition makes patients vulnerable to infection, which puts a strain on patients’ already weakened immune systems. BeyondSpring Inc. has shared clinical data on Plinabulin, its asset for preventing chemotherapy-induced neutropenia (CIN), that points to it potentially standing as a better option than a current gold-standard neutropenia therapy.
 
While Neulasta, a current standard, is meant to activate the bone marrow to encourage the body to produce neutrophils, “Clinical data suggest that a large proportion of these neutrophils appear to represent immature neutrophils, which typically make their way to the tumor tissue, and tip the immune balance in the tumor into an immune-suppressive microenvironment,” BeyondSpring explains.
 
“While both Plinabulin and Neulasta monotherapy demonstrated equal effects in the prevention of CIN in terms of how often and how long patients experienced severe neutropenia in Study 105, this added demonstration of a potentially superior immune profile over Neulasta has distinct advantages. We now recognize the importance of our immune system in fighting cancer, and the avoidance of suppression of our immune system has the potential to result in better cancer outcomes and prognosis. A leading trend is to combine immunotherapy with chemotherapy, and the latter is known to induce CIN. With immune/chemotherapy combination, Plinabulin has the potential to offer advantages over Neulasta and G-CSFs in general for the prevention of CIN, to enable the best possible immune therapeutic efficacy,” said Dr. Ramon Mohanlal, executive vice president and chief medical officer at BeyondSpring.
 
In a study of patients with non-small cell lung cancer, Plinabulin proved comparable to Neulasta. When examining NLR (Neutrophil-to-Lymphocyte Ratio) and LMR (Lymphocyte-to-Monocyte Ratio), “Plinabulin did not show NLR>5 or LMR <3.2 values. Promyelocytes or myelocytes were observed in 77 percent of patients given Neulasta, compared to 14 percent of patients given Plinabulin (p<0.001), and neutrophil bands were observed in more than 25 percent of patients given Neulasta, compared to 0% of patients given Plinabulin (p<0.03),” according to a company press release. BeyondSpring added that “NLR values of >5 and LMR values of <3.2, as well as immature neutrophils, are associated with immune suppression and poor cancer prognosis.”
 
“Not only does Plinabulin appear to have immune-enhancing anticancer potential, but there is growing evidence supporting a superior product profile for the prevention of CIN. We previously reported a bone pain benefit with Plinabulin over Neulasta. Plinabulin prevents not only chemotherapy-induced neutropenia, but also chemotherapy-induced thrombocytopenia. This new observation of avoidance of an immune suppressive potential as was observed with Neulasta adds to the list of differentiating features observed in clinical trials to-date for Plinabulin and sets the stage for Plinabulin as a novel CIN treatment with potential for a superior product profile,” commented Dr. Lan Huang, CEO and co-founder of BeyondSpring.
 

Altering cancer metabolism helps treatments attack tumors
 
LONDON—In news from Cancer Research UK, it seems that restricting the ability of cancer cells to metabolize sugar could make oncolytic viruses more effective at attacking them, at least according to results described in a study published recently by the journal Cancer Research.
 
As Cancer Research UK notes, viruses that are trained to attack cancer cells—known as oncolytic viruses—can kill tumors without affecting healthy cells nearby. They normally work by invading the cells, multiplying and destroying the tumor from inside, and variations of them are being tested in clinical trials now.
 
In this new study, a team of scientists exposed lung, ovarian and colon cancer cells—as well as mouse models—to conditions similar to those in the human body, and investigated how manipulating cell metabolism can make cancer more vulnerable to oncolytic viruses.
 
In the lab, scientists usually keep cells at the perfect temperature and provide them with lots of glucose, as it’s easier to grow and store them this way. In this study, the researchers changed the lab conditions to make them reflect what actually happens in the human body, where sugar levels are much lower.
 
They found that oncolytic viruses worked better when less glucose was available. To investigate whether they could make the virus work even harder, the researchers then used a drug to restrict the cancer cells’ ability to metabolize sugar (its energy source) to see if this optimized the virus’ cancer killing capability. They found that reducing sugar levels allowed the virus to multiply much faster, making treatment more effective and destroying cancer quicker.
 
“Our research in the lab showed that restricting the amount of sugar available to cancer cells makes these cancer-attacking oncolytic viruses work even better,” said Arthur Dyer, lead author and Cancer Research UK-funded Ph.D. student from the University of Oxford. “We already know that this virus is effective against cancer—and this sugar-starving technique is a way to make it even better.”
 
This approach may also improve how potential cancer drugs are investigated in the lab.
 
Added Dyer: “When studying any kind of drug in the lab, we keep the cells in very high sugar conditions; it’s a bit like soaking them in Lucozade. But this doesn’t reflect the conditions that these cells would be exposed to in the body, which are normally much poorer—in cancer, they’re even worse because tumors typically have poor circulation. Our approach is more realistic in mimicking the conditions in the human body, which ultimately may help us to better predict how patients will respond to drugs well before any trials are planned.”
 
However, the researchers caution that their early findings should not be misinterpreted by patients who are looking to optimize treatments.
 
“It’s important to remember that changing your diet is not enough to starve cancer cells of sugar,” stressed Prof. Len Seymour, Cancer Research UK-funded study author from the University of Oxford. “A lot of people think that carbohydrates are bad, but that’s not the case—we need them, and cutting out sugar won’t cure cancer. Because cancer gobbles up glucose so quickly, the cells are very vulnerable to attack from a drug that targets the sugar pathway. The same effect cannot be achieved by eliminating sugar from your diet.”
 
The team is aiming to test its glucose-limiting approach to improving oncolytic virus treatment in clinical trials to assess whether it could be successfully implemented in cancer patients.
 
“By making treatments work more effectively, we hope that patients will be able to see positive results faster than before,” concluded Dr. David Scott, Cancer Research UK’s director of discovery research. “The next step is to test whether this approach works in clinical trials, and to find out which cancers respond best.”
 

Forward momentum for Nkarta
 
SOUTH SAN FRANCISCO, Calif.—Early November saw Nkarta Therapeutics share preclinical data at this year’s SITC meeting regarding its natural killer (NK) cell therapies.
 
NK cells can differentiate between healthy and cancerous cells, and are also capable of triggering the adaptive immune system into an immune response against threats. In cancer patients, however, this response isn’t potent enough to eradicate the cancer. The company’s approach genetically engineers and expands populations of NK cells to boost their expression of NKG2D, a tumor-targeting receptor, and the cytokine IL-15, which can extend their potency and lifespan. Nkarta tested its NK cells in a xenograft osteosarcoma model, and saw the tumors shrink significantly, with complete tumor suppression for more than two months.
 
“Natural killer cells have a distinct role in our bodies to help us fight pathogens and cancer,” commented James Trager, senior vice president of research and development at Nkarta. “However, when cancer progresses it can overwhelm the natural defense mechanism of these cells. Our technology can reinvigorate NK cells, significantly enhancing their native tumor recognition and killing. We look forward to generating additional preclinical data to support advancement into the clinic in the future.”
 
Nkarta is aiming to produce off-the-shelf, allogeneic therapies based on its NK cells, ones that can deal with the associated immune response.
 

The more, the merrier
 
LA JOLLA, Calif.—In one of the latest efforts toward developing a cancer vaccine, Scripps researchers have engineered a vaccine capable of working synergistically with additional therapeutics.
 
By adding the adjuvant Diprovocim, a toll-like receptor TLR1/TLR2 agonist, to a cancer vaccine, the research team saw a significant difference in survival rates.
 
In mice with aggressive melanoma who had been treated with anti-PD-L1, the mice that received the cancer vaccine and Diprovocim saw a 100-percent survival rate over 54 days. By comparison, 0 percent of mice who received only the vaccine survived, while 25 percent survived in the cohort that received the vaccine and an adjuvant known as alum.
 
According to their research, the addition of Diprovocim supported the vaccine by stimulating the production of tumor-infiltrating leukocytes. In the mice who had received Diprovocim and the vaccine, attempts to re-challenge their systems with the melanoma tumors failed.
 
As noted in the study’s abstract, “Diprovocim-adjuvanted ovalbumin immunization promoted antigen-specific humoral and CTL responses and synergized with anti–PD-L1 treatment to inhibit tumor growth, generating long-term antitumor memory, curing or prolonging survival of mice engrafted with the murine melanoma B16-OVA. Diprovocim induced greater frequencies of tumor-infiltrating leukocytes than alum, of which CD8 T cells were necessary for the antitumor effect of immunization plus anti–PD-L1 treatment.”
 
“This co-therapy produced a complete response—a curative response—in the treatment of melanoma,” summarized Scripps Research's Dr. Dale Boger, who co-led the study with Nobel laureate Dr. Bruce Beutler of UT Southwestern.
 
Moving forward, the team intends to explore the vaccine design further and test it with cancer therapeutics besides anti-PD-L1.
 

Telix and Nihon to collaborate on actinium renal cancer therapeutics
 
MELBOURNE, Australia & TOKYO—Telix Pharmaceuticals Ltd., a clinical-stage biopharmaceutical company focused on the development of diagnostic and therapeutic products based on targeted radiopharmaceuticals or “molecularly-targeted radiation,” and Nihon Medi-Physics Co., Ltd. (NMP), a manufacturer and supplier of radiopharmaceuticals and related products in Japan, have announced the signing of a collaboration agreement to jointly evaluate the feasibility of 225Ac-labeled (actinium) antibodies for the treatment of clear-cell renal cell cancer (ccRCC).
 
In order to materialize theranostics (a concept of integrating therapeutics and diagnostics), NMP is actively developing alpha-emitting radionuclide (such as 225Ac)-based therapeutic pipeline, following the decision to build a new R&D site to produce radionuclides including 225Ac. In comparison to other types of radionuclides, alpha-emitters have relatively higher energy to damage cancer cells and shorter energy deposit range to minimize damages to the peripheral normal cells. Therefore, 225Ac, an alpha-emitting nuclide, is expected to have significant clinical potential for the treatment of cancer via nuclear medicine techniques. The parties will collaborate to apply NMP’s novel linker chemistry to Telix’s anti-CAIX antibodies and jointly conduct proof-of-concept studies.
 
“Part of the attractiveness of this collaboration with NMP is that Telix’s 89Zr-girentuximab (TLX250) PET imaging tracer also targets CAIX, and can therefore select patients for therapy,” said Dr. Shintaro Nishimura, Telix Pharmaceuticals’ Japan president. “Through this important collaboration with NMP, we hope make theranostics a reality in Japan.”
 
Added NMP President Hisashi Shimoda: “NMP views theranostic radiopharmaceuticals as a growth driver for our business. This collaboration with Telix, who is extensively developing products in the oncology field, is expected to impact positively on our business strategy. NMP has long-standing experience and skills in the manufacture and supply of radiopharmaceuticals, and Telix’s product portfolio, combined with our expertise, will together contribute greatly to moving closer toward the real theranostics.”
 

IMV moves to develop DPX-Survivac as monotherapy for recurrent ovarian cancer
 
DARTMOUTH, Nova Scotia—IMV Inc., a clinical-stage immuno-oncology company, announced in mid-November an amendment to its Phase 1b/2 clinical trial evaluating the safety and efficacy of IMV’s lead candidate, DPX-Survivac, in combination with either 100 mg or 300 mg of epacadostat in patients with recurrent ovarian cancer.
 
A review of new data from the Phase 1b portion of the clinical trial demonstrates a high response rate and a durable clinical benefit in a subpopulation of patients with a clinical marker predictive of a response to DPX-Survivac and correlated to its novel mechanism of action. New data include:
  • Efficacy signals in the subpopulation of patients who received 100 mg dose epacadostat included 100-percent tumor regressions and 100-percent disease control rate; and 60 percent of these patients reached a best response of a partial response
  • Long duration of clinical benefit observed in responders with a median duration of 590 days, including one patient that has passed the two-year mark without disease progression
  • Clinical benefit correlated to DPX-Survivac’s MOA and clinical study primary endpoints: survivin-specific T cells in the blood and T cell infiltration into tumors
  • The safety profile of DPX-Survivac is consistent with the profile observed in the company’s previously reported studies.            
Based on 300 mg cohort results, IMV and Incyte have agreed to stop dosing patients with epacadostat. IMV will continue the Phase 1b/2 trial as a monotherapy study evaluating DPX-Survivac in the recurrent ovarian cancer subpopulation. IMV will inform and work with investigators to appropriately modify the study in a manner consistent with the best interests of each patient.
 
IMV and Incyte will continue to explore the potential of additional combination studies.
 
“The goal of the trial was to evaluate combination therapies. However, the new data indicate that DPX-Survivac shows activity as a monotherapy in late-stage patients, which can potentially translate into  clinical benefit,” said Frederic Ors, CEO of IMV. “In parallel to the amended monotherapy trial, we will continue to investigate other combinations with our lead product candidate as we continue our work to deliver new immunotherapy options that may benefit more patients in multiple cancers.”
 
“We are very pleased that the Phase 1b trial results to date validate the mechanism of action of DPX-Survivac, helping us to identify patients more likely to benefit from our drug candidate,” added Dr. Gabriela Nicola Rosu, chief medical officer at IMV. “Identifying which patients have the greatest potential for responding to a drug candidate is key for the success of immunotherapy clinical trials, and we look forward to continued work with investigators and trial sites to advance the study of DPX-Survivac to help address the significant unmet medical needs of these patients.”
 

Establishing immunotherapy for pediatric liver cancer
 
HOUSTON—As part of a $6-million effort to establish new therapies for high-risk pediatric liver cancer, Navin Varadarajan, associate professor of chemical and biomolecular engineering at the University of Houston, will modify T cells to recognize and kill glypican-3, a molecule found in liver cancer cells.
 
With two previous awards from the Cancer Prevention & Research Institute of Texas (CPRIT), Varadarajan is working to improve effectiveness of T cell immunotherapy. On this CPRIT multi-investigator research award, he joins Andras Heczey, a physician researcher at Baylor College of Medicine, in examining one of the most common forms of liver cancer in adolescents: hepatocellular (HCC) carcinoma. HCC patient survival rates are under 30 percent.
 
No effective cure is available for most metastatic hepatocellular tumors. Current treatment includes surgical resection or liver transplantation in combination with dose-intensive chemotherapy regimens. T cell-based immunotherapy has worked in other types of cancers, like leukemia and lymphoma. The team at Baylor will isolate the T cells and modify them with synthetic receptors, and then Varadarajan will get to work.
 
“We have a platform for documenting how well T cells work, and we will use it to determine which T cell properties are essential in fighting the cancer cells,” said Varadarajan, whose team built the microscopy-based methods for monitoring cellular function.
 
Once determined, certain functions can be added or subtracted through genetic editing to make the T cell the best cancer fighter possible. The modified cells will deliver targeted and tailored therapy in clinical trials at Baylor.
 
“The hope is to get consistent and durable patient responses in pediatric HCC by using the power of immunotherapy,” said Varadarajan, who credits CPRIT with the steps forward in immunotherapy. “Texas taxpayers are amazing for funding CPRIT. Much of this research would not be possible without it.”
 
 
Code: E121835

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