Iovance therapy appears safe, effective in melanoma, cervical cancer

Data from two trials evaluating the safety and efficacy of adoptive cell transfer with autologous tumor-infiltrating lymphocytes showed promising overall response rates for the treatment of advanced metastatic melanoma and cervical cancer, according to results presented at ASCO Annual Meeting.

The study data show that investigational therapy LN-144 (lifileucel; Iovance Biotherapeutics) had a 38% overall response rate in patients with advanced metastatic melanoma. Investigational therapy LN-145 (Iovance Biotherapeutics) conferred a 44% ORR in patients with advanced cervical cancer.

Both trials used an identical treatment method that involve isolating a patient’s tumor-infiltrating lymphocytes (TILs) from a resected portion of their tumor, and then multiplying them in a laboratory. The manufacturing process takes 22 days.

Patients in both trials received lymphodepletion for 1 week with cyclophosphamide or fludarabine and were given up to six doses of interleukin-2 after the infusion of LN-144/LN-145.

“Taking the tumor out of the patient allows us to grow these lymphocytes to a far greater number,” Amod Sarnaik, MD, surgical oncologist with the Melanoma Center of Excellence at Moffitt Cancer Center and lead author of the LN-144 study, told HemOnc Today.

“These patients are treatment refractory, so their disease has progressed on the best FDA-approved treatments that are available,” he said. “Our treatment has a 38% response rate. You can walk around the ASCO exhibit hall and you are not going to find very many, if any, treatments that can match that response rate.”

There are few effective treatment options for patients with advanced cervical cancer, according to Amir Anthony Jazaeri, MD, vice chair for clinical research and the director of the Gynecologic Cancer Immunotherapy Program in the department of gynecologic oncology and reproductive medicine at The University of Texas MD Anderson Cancer Center.

“It’s nice to have a process that’s only 22 days, because these are patients with metastatic disease and if they wait too long, they can experience progression,” Jazaeri told HemOnc Today.

He explained that the entire process takes about 2 weeks, from the start of lymphodepletion, followed by TIL infusion, ending with adjuvant interleukin-2 therapy.

TILs for metastatic melanoma

In the phase 2, open-label, multicenter clinical trial, 66 patients (median age, 55 years; 59% men)with stage IIIC or stage IV metastatic melanoma were infused with cryopreserved lifileucel (mean cells infused, 27.3 × 10⁹).

Patients had received a mean of 3.3 previous therapies (range, 1-9) before infusion, including PD-1 inhibitors (100%), CTLA-4 inhibitors (80%) and BRAF/MEK inhibitors (23%). Study patients also had a high baseline tumor burden (106 mm mean target lesion sum of diameters).

https://www.healio.com/hematology-oncology/melanoma-skin-cancer/news/online/%7B245df162-58bc-4225-b446-a92498423403%7D/tumor-infiltrating-lymphocyte-therapy-appears-safe-effective-in-melanoma-cervical-cancer

ASCO: Sanofi’s anti-CD38 myeloma combo ups responses, extends lives

Sanofi’s anti-CD38 antibody isatuximab added to the standard of care for relapsed multiple myeloma extended patients’ lives and nearly doubled the number of patients for whom the standard of care worked. The phase 3 data, presented Sunday at the annual meeting of the American Society of Clinical Oncology, showed that the isatuximab combination shrank tumors in 60% of patients compared to 35% of patients taking the standard of care alone.

The standard of care is a combination of Celgene’s Pomalyst (pomalidomide) and the corticosteroid dexamethasone—dubbed pom-dex—which is usually given to patients who have relapsed after undergoing multiple treatments.

“Myeloma patients go through a journey where they get treated, they go into remission, and then they relapse, get treated and go into remission,” Sanofi R&D head John Reed told FierceBiotech. “[Pom-dex] is usually the third line, when they’ve already been through this a couple times—by the time the third relapse occurs, there’s not much to offer patients.”

Frontline treatments succeed in the majority of patients, but multiple myeloma is still considered incurable—“everybody eventually relapses,” Reed said. Sanofi is working on isatuximab as an agent that can boost the efficacy of multiple myeloma treatments at various stages of the disease.

The phase 3 study enrolled 307 patients in 24 countries with relapsed or refractory multiple myeloma who had received at least two prior therapies. They received either pom-dex alone or pom-dex in tandem with isatuximab.

The isatuximab combo kept cancer at bay for a median of 11.5 months, a five-month improvement over the 6.5 months for pom-dex alone. It also increased the number of patients for whom pom-dex worked—the combo shrank tumors in 60% of patients, compared to 35% for the standard of care alone. What’s more, of the patients who responded to treatment, the isatuximab combo worked faster, taking a median of 35 days to get a response versus 58 days for pom-dex alone.

“Isatuximab in combination with pomalidomide and dexamethasone resulted in an impressive 40% reduction in the risk of progression or death compared to pomalidomide and dexamethasone alone,” said the study’s principal investigator, Paul Richardson, M.D., in a statement. “This outcome is noteworthy because this trial included a particularly difficult-to-treat, relapsed and refractory patient population that was, in my view, highly reflective of real-world practice.”

An analysis showed that the isatuximab combo performed similarly in different subgroups, including the elderly and people with poor kidney function.

“It gives you real confidence in the robustness of the data that every subgroup we looked at, you saw that adding isatuximab provided additional benefit,” Reed said. “When you see data sets where some groups benefit and others don’t, you wonder how strong are these data?”

Isatuximab showed early promise as a single agent, but Sanofi felt it would be best used to improve existing cancer treatments. It is testing it alongside earlier-line treatments such as Takeda’s Velcade and Amgen’s Kyprolis and is thinking about combining it with experimental treatments like the bispecific antibody it’s working on with Regeneron, Reed said.

Sanofi has filed isatuximab for approval in the U.S. and Europe and doesn’t expect any hiccups with the regulators, Reed said.

“We should be a player in myeloma pretty soon—that gives us an anchor point around which to build. Certainly, building vertically within myeloma—going to first-, second- and third-line therapy—[will involve] bringing in novel combination partners, so there will be a quite robust effort there.”

Isatuximab, like Johnson & Johnson’s blockbuster Darzalex (daratumumab) targets the CD38 receptor found on multiple myeloma cells to attack the cancer. Sanofi thinks it could one-up its rival thanks to a different different mechanism.

“Isatuximab binds to a different epitope on the CD38 target than daratumumab and in the laboratory, you can show mechanistic differences and how that affects the attack on the tumor,” Reed said.

“Isatuximab … induces a direct cell suicide signal in the myeloma cell, which is something daratumumab doesn’t do,” he said. “Also, CD38 is an enzyme and has what is called ecto-enzyme activity, where the enzyme activity is on the surface of the cell, not the interior of the cell.” Isatuximab blocks this activity strongly while Darzalex does so weakly, Reed said. Sanofi believes this combats the production of metabolites by the cell that tamp down the immune system in the tumor microenvironment.

Of course, Reed said, it isn’t an apples-to-apples comparison and Sanofi will need to replicate the success of isatuximab in the lab into patients in the clinic. But if it works, it will be a success story for Sanofi’s efforts to build more of its pipeline from internal research rather than through partnerships.

https://www.fiercebiotech.com/biotech/asco-sanofi-s-anti-cd38-combo-boosts-responses-extends-lives-advanced-multiple-myeloma

Gates, Bezos-backed Alzheimer’s accelerator issues first awards

The Alzheimer’s Drug Discovery Foundation (ADDF) has selected the first four research ideas to be funded through its Diagnostics Accelerator program aimed at developing new tools and biomarkers for the disease and its related dementias.

Backed by some of the richest people in the world—including Bill Gates, Jeff and MacKenzie Bezos and ADDF co-founder Leonard Lauder—the accelerator program plans to award up to $50 million over the next three years. It expects to spend up to $10 million this year on at least 10 projects, with the first four totaling up to about $3.5 million.

The accelerator sent out an additional request for proposals for digital tests and biomarkers this April and plans to issue those awards before the end of the year. The first set of awardees focuses on cheaper, scalable diagnostics such as blood tests and eye scans.

“Unlike heart disease and cancer, we lack simple and cost-effective diagnostic tools and biomarkers that are critical to finding ways to prevent and treat Alzheimer’s disease,” Howard Fillit, the foundation’s executive director and chief science officer, said in a statement.

“Once we have them, we will better understand how Alzheimer’s progresses and make clinical drug trials more efficient and rigorous,” Fillit said.

The projects include a grant of up to $2 million to Amoneta Diagnostics and its chief scientific officer, Saliha Moussaoui. Amoneta based in France, just north of Basel, Switzerland, is developing a liquid biopsy to predict mild cognitive impairment and early Alzheimer’s, by measuring two types of RNAs that are stable in the bloodstream.

Researchers at the University of Gothenburg in Sweden working under Professor Kaj Blennow will receive $500,000 for their work on a blood test aimed at detecting brain-derived tau protein fragments similar to the ones found in the cerebrospinal fluid.

University of Edinburgh research fellow Tom MacGillivray and his lab, meanwhile, will get nearly $490,000 to develop their retinal biomarkers to help track neurodegeneration and changes in the eye’s vasculature, using a cloud-based system for analyzing images.

Associate Professor Peter van Wijngaarden of the Centre for Eye Research Australia, through the University of Melbourne, will get just over $420,000 to examine a simplified eye scan to detect amyloid in the retina ahead of cognitive decline. His team is also developing a more portable and inexpensive camera that aims to replace PET imaging or invasive fluid tests and biopsies.

https://www.fiercebiotech.com/medtech/gates-and-bezos-backed-alzheimer-s-accelerator-issues-first-diagnostic-development-awards

ASCO: AZ, Merck’s Lynparza in pancreatic cancer halves progression risk

AstraZeneca and Merck’s Lynparza is on a roll when it comes to making headlines at the American Society of Clinical Oncology (ASCO) annual meeting—and doing it in some of the toughest-to-treat cancers out there. And it wasn’t going to stop this year.

Sunday, the drugmakers trumpeted phase 3 data showing the PARP inhibitor slashed the risk of disease worsening or death by 47% in patients with germline BRCA-mutated pancreatic cancer that hadn’t progressed after an initial round of chemo. Lynparza patients in the study, dubbed Polo, went a median 7.4 months without their cancer advancing compared with just 3.8 months for placebo patients.

At the one-year mark, Lynparza had kept cancer at bay for 34% of patients versus placebo’s 15%. And at the two-year mark, Lynparza continued the trend, staving off progression in more than twice as many patients as placebo did—at 22% and 10%, respectively.

The results are “very exciting” considering “we are now able to offer a chemo-free option in maintenance to patients who for over a decade haven’t had any meaningful improvement,” Dave Fredrickson, executive vice president and global head of AstraZeneca’s oncology business unit, said.

Pancreatic cancer has been a tough nut for drugmakers to crack, in part because companies haven’t had a target to go after in development—until now.

“In the absence of those, chemotherapy becomes your only option, which is not a great option for patients relative to … other tools we have at our disposal in other tumor types,” Fredrickson said, adding “this will absolutely redefine the standard of care for gBRCA pancreatic cancer.”

And the results will change something else, too, he predicts. “What this will do, assuming it’s approved, is create the imperative to make sure we’re testing for BRCA outside of just women’s cancers,” he said. The company has plenty of experience at driving new testing habits, he noted, including with Lynparza in BRCA-mutated ovarian cancer.

“I have every confidence that … in a disease that is as difficult to treat as pancreatic cancer, we will be able to work together with the community” to increase testing, and “I believe that once we know that patients are gBRCA, it should be very clear that they should be treated with Lynparza,” Fredrickson said.

In the last three years, Lynparza has ranked among ASCO’s biggest newsmakers with data from three separate disease areas. Last year, it made waves with a Zytiga combo in prostate cancer, and the year before, it posted big survival numbers in breast cancer.

https://www.fiercepharma.com/pharma/embargoed-til-sunday-6-2-at-730-am-et-az-merck-s-lynparza-nearly-halves-pancreatic-cancer

Imfinzi only immunomed getting 3 year survival in non-small cell lung cancer

Data presented at ASCO 2019 showed 57% of patients
alive at three years vs. 43.5% on placebo

AstraZeneca has presented three-year overall survival (OS) results from the Phase III PACIFIC trial of Imfinzi (durvalumab) in unresectable, Stage III non-small cell lung cancer (NSCLC) during the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

These latest results show a durable and sustained OS benefit in patients with unresectable, Stage III NSCLC who had not progressed following concurrent chemoradiation therapy (CRT), a previous standard-of-care (SoC) treatment. The OS rate was 57% at three years for patients receiving Imfinzi vs. 43.5% for placebo following concurrent CRT. Median OS was not yet reached with the Imfinzi arm vs. 29.1 months for placebo.

Dave Fredrickson, Executive Vice President, Oncology Business Unit said: “These findings for Imfinzi are another example of our focus on bringing long-term survival benefits to patients who still have a chance of being cured. These three-year survival results further establish the PACIFIC regimen as the standard of care for these patients, and we are optimistic this survival trend will continue as we move towards the five-year landmark in this curative-intent setting.”

Results build on the primary two-year OS analysis that was published in The New England Journal of Medicine in September 2018 and demonstrated a significant OS benefit for treatment with Imfinzi vs. placebo after CRT, regardless of PD-L1 expression. The primary analysis showed Imfinzi reduced the risk of death by 32% (HR 0.68, [99.73% CI, 0.47-0.997], p=0.0025).

With the additional year of follow up, the latest results for Imfinzi showed consistent and durable efficacy, maintaining a 31% reduction in the risk of death vs. placebo after CRT (HR 0.69, [95% CI 0.55-0.86]).

https://www.astrazeneca.com/media-centre/press-releases/2019/imfinzi-is-the-only-immunotherapy-to-demonstrate-overall-survival-at-three-years-in-unresectable-stage-iii-non-small-cell-lung-cancer02062019.html

Spectrum Has Results from 2 Phase 3 Neutropenia Med Trials at ASCO

Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with a primary focus in hematology and oncology, today announced integrated analysis results from two Phase 3 clinical trials of ROLONTIS. ROLONTIS is a long-acting granulocyte colony-stimulating factor (G-CSF) being studied as a treatment for neutropenia in patients undergoing myelosuppressive cytotoxic chemotherapy.

The analysis found that integrated efficacy and safety data from the two identically designed Phase 3 trials – ADVANCE and RECOVER – were consistent with results from the individual trials, demonstrating that ROLONTIS was non-inferior to pegfilgrastim in the reduction of duration of severe neutropenia (DSN) in all four cycles of treatment. The summary was presented today during a poster session at the American Society of Clinical Oncology 2019 Annual Meeting in Chicago.

https://apnews.com/Business%20Wire/cb5cb9beafd340968f80b8d94afa2ccf

Celgene: 4 Things To Watch for at ASCO 2019

More than 32,000 oncologists, researchers, nurses and patient advocates from around the world are expected this week for the 55^th American Society of Clinical Oncology (ASCO) Annual Meeting to learn about the latest advances in cancer research and innovations in cancer care.

With more than 2,400 abstracts accepted for presentation at the conference and more than 3,200 additional abstracts accepted for online publication, we’re highlighting four areas of research being discussed at ASCO that shouldn’t be missed.

1. Exploring CAR T Cell Therapies for Chronic Lymphocytic Leukemia and Certain Lymphomas

Some anticipated studies are focused on the development of chimeric antigen receptor (CAR) T cell therapies as oncologists are excited to learn as much as possible about this innovative therapeutic class.

Researchers will be presenting new data from Celgene-sponsored studies on the potential durability of patients’ responses to an investigational CAR T-cell therapy in patients with relapsed/refractory mantle cell lymphoma and the impact of this investigational therapy on health-related quality of life in patients with diffuse large B-cell lymphoma (DLBCL). As well, researchers will address the adverse events (AEs) of these investigational treatments observed in patients with various cancers.

Some of the cancers for which CAR T-cell therapies are being explored as potential treatments include chronic lymphocytic leukemia and relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL).

2. Targeting Janus Kinase 2 (JAK2) in Myelofibrosis

The only potential curative treatment option for myelofibrosis is a stem cell transplantation, but many patients are ineligible for the procedure. This year at ASCO researchers will present results from a study focusing on a therapy of a wholly owned subsidiary of Celgene that targets a protein called Janus Kinase 2 (JAK2).

More options are needed for these patients, and data at ASCO will reveal what is on the horizon.

3. Targeting Cereblon in Relapsed/Refractory Multiple Myeloma

Over the past decade, researchers have been working to uncover the role of cereblon in the biology and treatment of multiple myeloma. Cereblon is a protein that functions as part of the cellular machinery that disposes proteins no longer needed by the cell.

At ASCO 2019, researchers will present data from a Celgene-sponsored study on an investigational compound capable of co-opting cereblon as a mediator of the targeted protein degradation mechanism of certain target proteins. Physicians are keen to identify new treatment options since multiple myeloma is incurable and patients with the disease often cycle through multiple therapies over the course of their treatment.

4. Immunotherapy Combinations for Relapsed/Refractory Indolent Non-Hodgkin’s Lymphoma

Many patients with indolent (slow growing) NHL, such as follicular lymphoma, may experience multiple relapses that require several rounds of therapy. Their durability of response can also diminish with each line of therapy.

At this year’s ASCO, oncologists will present new analyses from ongoing Celgene-sponsored studies of a new combination regimen to treat certain types of indolent NHL.

https://www.celgene.com/asco-4-things/