Clinical Catch-up from Last Week: June 1-June 7

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Here’s a look at some of last week’s clinical trial announcements, including some from the American Society of Clinical Oncology (ASCO) Annual Meeting you might have missed.

Bellicum Pharmaceuticals announced updated safety and activity data at ASCO for its BPX-601 from a Phase I/II trial in metastatic pancreatic cancer expressing prostate stem cell antigen (PSCA). “These updated results in patients with advanced pancreatic cancer showed that more intense lymphodepletion with Flu/Cy resulted in increased BPX-601 CAR-T cell expansion and prolonged persistence in patients treated with single-dose rimiducid,” stated Carlos R. Becerra, lead study investigator, oncologist and medical director of the Innovative Clinical Trials Center at Baylor University Medical Center. “Evidence of biological activity and stable disease was observed in this ongoing trial in these heavily pretreated patients who desperately need additional treatment options.”

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Provectus Biopharmaceuticals presented preliminary data on its ongoing Phase I trial at ASCO of single agent PV-10 for symptomatic neuroendocrine tumors (NET) metastatic to the liver. The trial is being conducted at The Queen Elizabeth Hospital in Adelaide, Australia. “Patients with neuroendocrine tumors remain a cancer population with high unmet medical need,” stated Dominic Rodrigues, vice chair of the company’s board of directors. “This poster describes Provectus’ continued progress towards demonstrating the widespread use of small molecule oncolytic immunotherapy PV-10 for the treatment of immunologically ‘cold’ or non-T-cell inflamed tumor types. Patients in this study experienced no safety concerns from single or repeated injections of PV-10 into the liver. Furthermore, we believe PV-10 treatment provided in this trial yielded encouraging, preliminary evidence of single-agent drug activity, including both local and systemic disease control.”

SELLAS Life Sciences Group presented Phase IIb data at ASCO of Nelipepimut-S (NPS) plus trastuzumab (Herceptin) in triple-negative breast cancer. “These ex vivo and in vivo results in TNBC patients, particularly the newly discovered correlation between mounting an immune response and remaining clinically relapse-free over time, provided a solid mechanistic rationale for the previously observed clinically meaningful and statistically significant prolongation in disease-free survival (DFS), and the significant decrease in the frequency of relapses identified by standard clinical follow-up, in favor of NPS plus trastuzumab,” stated Angelos M. Stergiou, president and chief executive officer of Sellas.

Also at ASCO, Progenics Pharmaceuticals presented long-term follow-up data from its Phase II trial of Azedra (iobenguane I 131) in patients with unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma (PPGL). As of Jan. 25, 2019, median overall survival time (OS) for all patients was 41.1 months; median OS was 17.5 months and 48.7 months in patients receiving one or two doses, respectively; the 12-month OS rate was 91%; and a tail of survival was noted, with OS of 73.1% at two years and 44.2% at four years.

Rakuten Medical presented at ASCO positive data from its Phase IIa clinical trial of its Photoimmunotherapy (PIT) platform. It looked at the safety and anti-tumor activity of RM-1929, an EGFR-targeted antibody conjugate PIT in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC). The company also presented trial design for its global Phase III trial. The overall response rate was 43%, including 13% complete responses and 30% partial responses. The median, progression-free survival was 5.2 months.

Genentech, a Roche company, announced the results from its Phase III BLOCKSTONE trial, conducted by Shionogi & Co. The trial evaluated Xofluza (baloxavir marboxil) in preventing influenza. The BLOCKSTONE trial evaluated a single dose of Xofluza compared with placebo in household members, both adults and children, in Japan who were sharing a household with someone with the flu. The infection was confirmed using a rapid influenza diagnostic assay. It was conducted by Shionogi during the 2018-2019 flu season in Japan.

Xofluza showed a significant preventive effect after a single oral dose. Only about 1.9% of patients who received Xofluza showed signs of the flu, compared to 13.6% of the placebo group. In terms of side effects, 22.2% of the Xofluza cohort showed side effects compared to 20.5% of the placebo group. No serious adverse events were reported.

Genentech also announced positive topline data from two Phase III trials evaluating Xolair (omalizumab) for adults with chronic rhinosinusitis with nasal polyps. The POLYP 1 and 2 Phase III trials both met co-primary endpoints and key secondary endpoints.

“The results from these pivotal studies provided further support that IgE plays a role in inflammatory and respiratory conditions, and showed that Xolair reduced the size of nasal polyps and associated symptoms that impact these patients’ quality of life,” Horning stated. “We plan to discuss these results with the FDA with the goal of bringing this new treatment option as soon as possible to people who do not experience relief with the current standard of care.”

The Institute of Cancer Research (ICR), London, and The Royal Marsden NHS Foundation Trust, presented clinical trial analysis at ASCO. The gist of the trial was that immunotherapy with chemotherapy, either by itself or in combination, is a more effective first-line treatment for head and neck cancer than standard aggressive chemotherapy.

The clinical trial involved 206 research centers worldwide. Patients were given Merck’s Keytruda in combination with platinum chemotherapy, Keytruda by itself, or chemotherapy by itself. The trial results found that the combination extended survival, and immunotherapy alone also worked well for some patients.

Atara Biotherapeutics, along with Memorial Sloan Kettering Cancer Center, presented an update at ASCO on the ongoing Phase I trial of mesothelin-targeted CAR-T for patients with mesothelin-associated malignant pleural solid tumors, primarily mesothelioma, who progressed after platinum-based chemotherapy. The treatment was well-tolerated and showed encouraging anti-tumor activity in combination with Keytruda.

“The updates to this study presented by our (Memorial Sloan Kettering) collaborators reaffirm mesothelin as a promising target for patients with advanced mesothelioma and establishes an important proof-of-concept advancement for CAR-T immunotherapy in solid tumors,” stated Christopher Haqq, executive vice president and chief scientific officer of Atara.”

VBI Vaccines at ASCO presented clinical data from Part A of the Phase I/IIa trial of VBI-1901 in recurrent glioblastoma (GBM). Part A of the trial is a dose-escalation phase and enrolled 18 patients across three dose cohorts. Part B is an extension of the optimal dose level. The vaccine was well-tolerated at all doses, with no safety signals seen, and although grade 2, 3 or 4 adverse events occurred in 66%, 22%, and 11% of participants, respectively, none were related to the vaccine’s immunoresponse. Six patients responded to VBI-1901, with evidence of robust boosting of cytomegalovirus (CMV)-specific immune responses against by glycoprotein B (gB) and pp65 antigens. Median progression-free survival (PFS) was longer among responders (14.5 weeks) compared to non-responders (6 weeks).

Dynavax presented at ASCO “increasingly favorable” results from its Phase Ib/II (SYNERGY-001) clinical trial of SD-101 and Keytruda in advanced melanoma patients who have not received checkpoint inhibitors before. SD-101 is a second-generation, Toll-like receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide. It is being evaluated in combination with Keytruda in advanced melanoma, metastatic or recurrent head and neck squamous cell cancer, and in high-risk breast cancer in collaboration.

Novartis released early-stage histology data in kidney transplants at the American Transplant Congress (ATC). The histology data suggests that the company’s iscalimab (CFZ533) might prolong the lifespan of kidney transplants, with the result of improving long-term outcomes for the transplant patients.

The data presented suggested that the iscalimab treatment preserved the quality of transplanted kidney grafts. It showed lower chronic allograft damage index (CADI) scores compared to tacrolimus. In addition, normal renal histology was observed in three of five patients, or 60%, on iscalimab compared to zero out of seven on tacrolimus. Low CADI scores are associated with better long-term outcomes. The company expects to confirm the data in an ongoing Phase IIb clinical trial.

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AstraZeneca’s Phase III ELEVATE-TN trial of Calquence (acalabrutinib) met its primary endpoint during an interim analysis in previously untreated chronic lymphocytic leukemia (CLL). Calquence in combination with obinutuzumab showed a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) compared to the chemotherapy-based chlorambucil and obinutuzumab. The study also met a key secondary endpoint of the drug as a monotherapy achieving improved PFS.

Takeda Pharmaceutical terminated its Phase III TOURMALINE-AL1 trial after it missed the first of two primary endpoints. The trial was evaluating Ninlaro (ixazomib) combed with dexamethasone, in patients with relapsed/refractory systemic light-chain amyloidosis. The drug was approved in 2015 by the FDA for multiple myeloma. In the trial, the drug failed to show an improvement in overall hematologic response compared to standard-of-care treatment.

University of California, Los Angeles (UCLA) researchers published the results of a Phase I and Phase II clinical trial of a three-drug combination in melanoma with a BRAF V600E mutations. The studies involved treating treatment-naïve patients with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib together with checkpoint inhibitor Keytruda.

“Earlier attempts to combine a targeted agent with an immune checkpoint inhibitor as a double-combination therapy had debilitating side effects for patients, and it was just too toxic to continue testing, so we went back to the drawing board,” stated Antoni Ribas, the paper’s senior author and professor of medicine at the David Geffen School of Medicine at UCLA. “We found that by using two targeted inhibitors, instead of just one, in combination with a checkpoint inhibitor, we could safely and effectively treat the cancer.”

Astex Pharmaceuticals, which is a member of the Otsuka group, and Otsuka Pharmaceutical Co. announced that their ASCERTAIN Phase III clinical trial of cedazuridine and decitabine (ASTX727) compared to decitabine IV alone hit its primary endpoints. The fixed-dose combination was being evaluated in adults with intermediate and high-risk myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML).

The primary endpoint was decitabine exposure equivalence of five-day dosing between oral doses of the combination and the IV dose of decitabine. The company plans to submit a New Drug Application (NDA) for the combination therapy with the FDA by the end of the year.

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