AstraZeneca, BMS Celebrate Cancer Trial Wins, Zebrafish Eye Mutation Linked to Cell Death

The outlook for cancer treatment looks bright as researchers and biopharma companies seem to be making breakthroughs and developing new insights daily. Sometimes, it’s a deeper understanding of the molecular mechanisms of the disease, while other times it’s finding new drugs or drug combinations that work for specific genetic mutations found in specific cancers.

BioSpace takes a look at this week's clinical and preclinical cancer advances.

Mutated Zebrafish Eyes Reveal Cell Death Insights

Researchers at the Okinawa Institute of Science and Technology (OIST) Graduate University discovered 15 years ago that certain zebrafish had significantly smaller eyes than their fishy brethren. Now, Ichiro Masai, Ph.D., who heads the developmental neurobiology unit at OIST with his former Ph.D. student Swathy Babu, PhD., has leveraged the mutation that caused this to better understand cell death. The findings could have enormous implications for cancer therapeutics and cell cycle regulation.

“Many cells that develop tumors reportedly have an issue with this protein,” Masai said. “Furthermore, the importance of the protein for regulating the cell cycle and helping DNA repair has also previously been hypothesized, but not rigorously tested.”

Masai theorized that in the small-eyed zebrafish the eyes were not developing properly because of an increased number of cell deaths. They worked with a protein called banp, which appeared to suppress tumors and regulate the cell cycle. But earlier research had been conducted on cell cultures or by deleting the gene in mice or other model organisms – which killed the embryos.

Zebrafish embryos, however, develop outside the body of the parent fish, in fish eggs. The banp gene is on chromosome 25. The researchers found a significant mutation in the gene in the mutated fish. Introducing yet another mutation in this gene in normal zebrafish caused their eyes to develop abnormally. They further discovered that banp plays an important role in converting DNA to RNA and promoted the expression of 31 genes.

“Banp seems to be a multiple regulator, influencing many different proteins, from DNA repair to cell duplication to tumor suppression,” Babu said. The mutations in the banp gene appear to be linked to cell death.

BMS and 2seventy bio Unlock the Potential of Cell Therapy in Multiple Myeloma

Bristol Myers Squibb and 2seventy bio announced positive topline results from the Phase III KarMMa-3 trial of Abecma (idecabtagene vicleucel) in multiple myeloma. Specifically, the drug is being studied in multiple myeloma that is relapsed or refractory (r/r) after two to four previous lines of therapy and refractory to the last regimen. Abecma is a first-in-class B-cell maturation antigen (BCMA)-directed CAR T cell immunotherapy. It is approved in the United States for adults with r/r multiple myeloma after four or more previous lines of therapy, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody.

The trial hit the primary endpoint of statistically significant improvement in progression-free survival (PFS). It also demonstrated improvement in the key secondary endpoint of overall response rate (ORR) compared to standard regimens.

“Results from the KarMMa-3 study clearly demonstrate the clinical benefit of using a CAR T cell therapy earlier in the multiple myeloma treatment paradigm,” Dr. Anne Kerber, M.D., SVP and head of cell therapy development at BMS said. “These data reinforce our commitment to unlocking the full potential of cell therapy as we strive to build on the company’s heritage of innovation in blood cancers and transform patients’ lives through science.”

HUTCHMED and AstraZeneca Score Mid-Phase Lung Cancer Win

HUTCHMED and AstraZeneca announced preliminary results from the Phase II SAVANNAH trial of Tagrisso (osimertinib) plus savolitinib in patients with EDGRm non-small cell lung cancer (NSCLC) with high levels of MET overexpression and/or amplification. The combination demonstrated an objective response rate of 49%. The highest ORR was seen in patients with high levels of MET who had not received previous chemotherapy. In patients whose tumors didn’t have high MET levels, the ORR was 9%.

“The current standard of care for patients with EGFR-mutated lung cancer who progress on targeted treatment is chemotherapy,” Dr. Cristian Massacesi, M.D., chief medical officer and oncology chief development officer for AstraZeneca said. “The results from SAVANNAH suggest savolitinib added to Tagrisso at the time of the disease progression could possibly provide these biomarker-selected patients with a potentially less toxic, more effective treatment option.”

HUTCHMED also announced that the Phase III FRESCO-2 trial of fruquintinib hit the primary endpoint in advanced, refractory metastatic colorectal cancer. The primary endpoint was overall survival. Also, a key secondary endpoint, a statistically significant improvement in PFS, was met.

Fruquintinib is a highly selective and potent oral inhibitor of VEGFR-1, -2 and -3.

“We are pleased to have successfully completed our first multi-regional clinical trial, FRESCO-2, to support the global registration of fruquintinib,” HUTCHMED CEO and CSO Weiguo Su, Ph.D. said. “It has already benefited patients with advanced CRC in China since its launch in 2018. It is also being evaluated alone and in combination with other agents in various tumor types in ongoing studies around the world.”