NEW YORK – The European Hematology Association Virtual Congress took place from June 9 to June 17. Below are brief summaries of some of the data presented on precision oncology therapies.
Roche presented data at the EHA Virtual Congress from three pivotal Phase III studies of venetoclax (Venclexta) — CLL14, MURANO, and VIALE-A — and highlighted the use of minimal residual disease, or MRD, as a measure of response in chronic lymphocytic leukemia and acute myeloid leukemia, as well as molecularly informed tailored treatment opportunities.
In a four-year, post-hoc analysis in the CLL14 study, researchers compared a year-long, fixed duration treatment of venetoclax plus obinutuzumab (Roche's Gazyva) against obinutuzumab plus chlorambucil in 432 patients with previously untreated CLL. At a median follow-up of 52.4 months, 74 percent of patients on venetoclax-obinutuzumab were progression free compared to 35.4 percent on obinutuzumab-chlorambucil. Importantly, 30 months after the end of treatment, 26.9 percent of venetoclax-treated patients still had undetectable MRD versus 3.2 percent in the chlorambucil-treated cohort.
The previously conducted, randomized Phase III MURANO study compared the safety and efficacy of venetoclax plus rituximab (Roche’s Rituxan) against rituximab plus bendamustine in 389 previously treated CLL patients, with or without 17p deletions. After four years of follow-up, the efficacy of venetoclax-rituximab over rituximab-bendamustine were sustained, especially for those who achieved undetectable MRD.
In a substudy from 2018, researchers enrolled another 34 relapsed or refractory CLL and gave them venetoclax-retuximab therapy again after they had progressed on the regimen initially or progressed on the bendamustine arm. In this portion of the study, they used comparative genomic hybridization and fluorescence in situ hybridization to characterize the genomic complexity of patients' cancers from first treatment to retreatment. At the EHA Virtual Congress, they reported that patients whose tumors gained unfavorable genomic characteristics, like increased clonality of 17p deletions, after initial venetoclax-rituximab treatment were less likely to achieve undetectable MRD upon retreatment.
"These data indicate the potential to tailor treatment approaches for patients with previously treated CLL based on genetic risk factors," Roche said in a statement.
In the Phase III VIALE-A trial, researchers compared venetoclax plus the hypomethylating agent azacitidine against just azacitidine in 431 previously untreated AML patients ineligible for intensive chemo. Patients in this study had IDH1/2, FLT3, and other mutational AML subtypes. VIALE-A showed that venetoclax-treated patients had longer overall survival and a higher chance at remission than those who received just azacitidine.
At the EHA Virtual Congress, researchers presented data from a post hoc analysis and showed that those who achieved undetectable MRD after venetoclax-azacitidine had improved survival compared to patients who were MRD-positive. Additionally, 12-month duration of response, overall survival, and event-free survival rates were 81.2 percent, 94 percent, and 83.2 percent, respectively, for those with undetectable MRD. Comparatively, 46.6 percent, 67.9 percent, and 45.4 percent of those with detectable MRD were still responding, alive, and event-free at one year.
"Undetectable MRD is emerging as a measure of disease response that may be useful to consider in treatment decision-making," Roche said in a statement announcing the updated data from these studies.
Mustang Bio presented interim data at the EHA Virtual Congress from a Phase I/II trial of its autologous CAR T-cell therapy, MB-106, for patients with relapsed or refractory, CD20-positive, B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia.
Of 15 patients who received the treatment, the overall response rate was 93 percent, and the complete response rate was 67 percent. Among the 11 patients who had follicular lymphoma, the overall response rate was 91 percent, and the complete response rate was 82 percent. The one patient with CLL achieved a complete remission.
According to Worcester, Massachusetts-based Mustang, at the time the data were submitted to the EHA, all patients who had achieved a complete response to MB-106 remained in remission.
In terms of the treatment's safety, six patients experienced cytokine release syndrome, but no CRS events were grade 3 or higher.
"MB-106 continues to demonstrate a very favorable safety and efficacy profile, as well as sustained complete responses," said Mazyar Shadman, a blood cancer specialist at the Fred Hutchinson Cancer Research Center and Mustang's collaborator on the trial. "This compelling clinical activity, including the complete remissions in 67 percent of the patients in the trial, demonstrates the potential of MB-106 as a viable CD20-targeted CAR T-cell therapy."
Gilead subsidiary Kite Pharma presented follow-up data from the ZUMA-5 clinical trial of axicabtagene ciloleucel (Yescarta) for patients with relapsed or refractory, indolent follicular lymphoma.
After a minimum of 18 months, axi-cel — which has already received accelerated approval from the US Food and Drug Administration for this patient population — demonstrated a 94 percent response rate, and median progression-free and overall survival had not been reached.
In a safety-evaluable cohort of 146 patients in the trial, 8 percent experienced grade 3 or higher cytokine release syndrome, and 21 percent experienced grade 3 or higher neurologic toxicities.
Kite also presented the results of an analysis comparing outcomes in 86 follicular lymphoma patients treated on the ZUMA-5 trial against 85 patients treated with current therapies in the SCHOLAR-5 trial. Among the ZUMA-5 patients, 95 percent responded to axi-cel after a median follow-up of 26.2 months as compared to 50 percent of patients who received other treatments in the sample SCHOLAR-5 cohort. While in ZUMA-5, the median progression-free survival and overall survival times that had not been reached at the time of analysis, the median progression-free and overall survival times in the SCHOLAR-5 cohort were 12.7 months and 59.8 months, respectively.
"The continued durable benefit demonstrated by axi-cel at nearly two years is exciting, and the substantial survival benefit over current therapies that we're seeing in the SCHOLAR-5 analysis is encouraging," Caron Jacobson, medical director of the Immune Effector Cell Therapy Program at the Dana-Farber Cancer Institute and lead investigator in ZUMA-5, said in a statement.
Innovent Biologics/IASO Biotherapeutics
Innovent Biologics and IASO Biotherapeutics presented data from a Phase I study of its BCMA-directed CAR T-cell therapy, IBI326, in relapsed or refractory multiple myeloma at the EHA Virtual Congress this week. The study showed a 97 percent overall response rate among 35 multiple myeloma patients, with 20 patients, or 57 percent, achieving complete response or stringent complete response. Thirty-four patients reached MRD negativity, and the median time to MRD negativity was 1.3 months.
Researchers also evaluated IBI326's activity in certain patient subsets including those previously treated with other BCMA-targeted therapies and patients with extramedullary multiple myeloma. Among eight patients with extramedullary multiple myeloma, all patients achieved a partial response or better on treatment with IBI326. Of the 10 patients previously treated with murine BCMA CAR T-cell therapy, nine achieved partial response or better and one had stable disease.
The trial also identified the recommended Phase II dose for IBI326 — 1.0 × 106/kg — and the company is currently studying the drug in a Phase II clinical trial.
"In particular, [IBI326] still shows good clinical benefits to the patients who received prior murine BCMA CAR-T treatment and provides better treatment options for patients with relapsed/refractory multiple myeloma," Hui Zhou, senior VP of medical development at Innovent, said in a statement.
Autolus Therapeutics released updated data for its CAR T-cell therapy obecabtagene autoleucel in relapsed or refractory, indolent B-cell lymphomas, or IBCL, and relapsed or refractory, adult acute lymphoblastic leukemia, or ALL.
Among 20 evaluable ALL patients, 17 achieved MRD-negative complete remission at one month. Event-free survival at 12 and 24 months was 50.2 percent. Among nine IBCL patents who had received an infusion, all achieved complete metabolic remission and had robust CAR T-cell engraftment, expansion, and persistence. Researchers also noted that obe-cel was well-tolerated in both IBCL and ALL patients.
"The stabilization of event-free survival at 50 percent between 12 months and 24 months of follow-up supports the curative potential of obe-cel as a standalone therapy for some adult ALL patients," Autolus CEO Christian Itin said in a statement. "The early data we presented in indolent B-cell non-Hodgkin lymphoma indicate a high level of clinical activity combined with a manageable safety profile and could represent a significant opportunity to expand the benefits of obe-cel treatment to a broader population of patients with B-cell malignancies."
Lexington, Massachusetts-based Curis presented data at the EHA Virtual Congress from a single-arm, Phase I/II dose-escalation study of CA-4948, a TLR pathway suppressor, in adults with acute myeloid leukemia or high-risk myelodysplastic syndrome. The aim of the study was to determine the Phase II dose of CA-4948, which researchers identified as 300 mg twice a day. As of an April 30 cutoff date, 10 out of 12 patients had bone marrow blast reductions at all tested doses of the drug, including five patients who had objective responses to the treatment. Three patients with SF3B1 and U2AF1 spliceosome mutations achieved complete remission and had no detectable leukemia cells in the bone marrow.
Researchers further highlighted that an AML patient with an SGF3B1 spliceosome mutation experienced a durable objective response for more than eight months and as of December 2020 had a complete remission in the bone marrow and subsequently achieved negative minimal residual disease. An AML patient with a FLT3 mutation who had relapsed on decitabine and venetoclax (Roche/AbbVie's Venclexta) and was refractory to gilteritinib (Astellas' Xospata), experienced a partial response on CA-4948 and had no detectable FLT3 mutations. A third AML patients who had four lines of chemotherapy had reduced IRAK4-L expression after CA-4948, and a full recovery of hematologic parameters.
"We are especially pleased with the outcomes seen to date for patients with spliceosome or FLT3 mutations," Curis CEO James Dentzer said in a statement. "While these are early days, and we have a limited set of patient data, we are very encouraged about the potential CA-4948 may have to become a disease-modifying alternative for these late-line patients, where no approved therapies currently exist."
Global drugmaker Gracell Biotechnologies released updated results from a Phase I, first-in-human study of its BCMA/CD19 dual-targeting CAR T-cell therapy, called GC012F, in relapsed or refractory multiple myeloma. Gracell developed the CAR T-cell therapy using its FastCAR next-day manufacturing platform. As of a Jan. 12 cutoff, the researchers have enrolled and treated 19 patients at three doses of GC012F. Eighteen patients, or 94.7 percent, had a very good partial response across dose levels, and all nine patients who got the highest dose of the drug (3x10^5 cells per kg) achieved MRD-negative, stringent complete response. Patients mostly had a low grade of cytokine release syndrome, though two patients had grade 3 CRS. None had grade 4 or 5 CRS or immune effector cell-associated neurotoxicity.
"These are very encouraging data, and they hold a promise for multiple myeloma patients with high-risk features and beyond, including those who have failed or are no longer responding to standard treatment options," Martina Sersch, Gracell's chief medical officer, said in a statement, adding that the company will expand the development program for GC012F globally and in earlier treatment settings.
This is a special selection of news items from the EHA Virtual Congress 2021 that may be of interest to our readers but has not previously appeared in Precision Oncology News.