In a flurry of weekend activity, oncology companies presented the latest clinical and preclinical data for cancer therapies during the American Association for Cancer Research’s virtual meeting. BioSpace provides an overview of some of the presentations.
Bristol Myers Squibb
Three Cycles Bristol Myers Squibb Checkpoint Inhibitor Opdivo (nivolumab) plus chemotherapy significantly improved pathological complete response (pCR) in patients with resectable non-small cell lung cancer stages Ib to IIIa (NSCLC). The Opdivo combination was compared to chemotherapy alone.
BMS is investigating the use of its immunotherapy treatments in earlier stages of cancer in the neoadjuvant, adjuvant and perioperative settings, as well as in chemoradiotherapy. The strategy offers an earlier way to target cancer cells that may have spread throughout the body without detection, BMS said. The company also said that the presence of a tumor during immunotherapy could trigger a stronger immune response, which could make treatment more effective.
Data from the CheckMate 816 study showed that 24% of patients treated with Opdivo and chemotherapy achieved pCR, compared with 2.2% of patients treated with chemotherapy alone, BMS said. For the study, pCR was defined so that there was no evidence of cancer cells in the resected tissue of the patients, as determined by a blinded independent pathology review. BMS found that patients treated with the combination showed consistent improvements in pCR regardless of PD-L1 expression levels, histologies, or stages of the disease. The combination of Opdivo and chemotherapy was well tolerated.
The combination of Opdivo and chemotherapy also met several secondary endpoints, including Major Pathological Response (MPR). According to BMS, four times as many study patients treated with Opdivo achieved an MPR of 36.9% versus 8.9%. According to the company, this means that only up to 10% of a patient’s tumor cells were left after neoadjuvant therapy.
The CheckMate 816 study is the first phase III randomized study to show a significant improvement in pathological response with a neoadjuvant immunotherapy combination in patients with resectable NSCLC, BMS said.
The results of the Bayer Phase III CHRONOS 3 study evaluating the intravenous combination of aliqopa (copanlisib) and rituximab in patients with relapsed indolent non-Hodgkin lymphoma (iNHL) showed a significant improvement in progression-free survival (PFS). With a median follow-up of 19.2 months, patients treated with this combination had a median PFS of 21.5 months compared to 13.8 months for patients treated with rituximab and placebo.
The highest overall response rate for the combination of aliqopa and rituximab was 80.8%. The placebo ORR was 47.7%. Of these, the complete response rates were 33.9% and 14.6% of the patients, respectively.
Aliqopa was approved in 2017 for the treatment of adult patients with relapsed follicular lymphoma (FL) who had previously received at least two systemic therapies.
According to Bayer, 60% of the relapsed iNHL patients included in the study had FL, 20.7% marginal zone lymphoma (MZL), 10.9% small lymphocytic lymphoma (SLL) and 8.3% lymphoplasmacytoidal lymphoma / Waldenström macroglobulinemia (LPL / WM ). The analysis of the subtypes will be presented at the AACR and published in The Lancet Oncology.
Kymera Therapeutics of Watertown, Massachusetts presented data highlighting the superiority of the dual targeting activity of its IRAKIMiD degrader, KT-413. The pre-clinical data presented showed that dual targeting of IRAK4 and IMiD substrates by KT-413 affects signaling and cell killing in diffuse large B-cell lymphoma (DLBCL) with MYD88 mutants in a mutant manner differs from IMiDs or selective IRAK4 targeting alone, according to the company. The data presented at the meeting indicated that KT-413 “uniquely inhibited both IRAK4-dependent MYD88-NFkB signaling and IMiD-substrate-dependent IRF4 upregulation and suppression of the type 1 interferon response, while CC -220 and KTX-545 only IRF4 type 1 interferon or MYD88-NFkB signaling. “
According to Kymera, IRAKIMiDs are novel heterobifunctional degraders designed to degrade both IRAK4 and IMiD substrates, including Ikaros and Aiolos, with a single small molecule.
KT-413 is initially being investigated for the treatment of relapsed / refractory MYD88 mutant DLBCL. Kymera said there is potential to expand the studies to other MYD88 mutant indications and IL-1R / NFkB-related malignancies. Kymera plans to bring KT-413 to the clinic in the second half of 2021.
Guardant Health of California and its partner Amgen presented data highlighting the effectiveness of a blood test that can advance precision oncology. The results presented at AACR show that Guardant’s Guardant360, Guardant360 CDx, and GuardantOMNI liquid biopsy tests were able to “detect clinically actionable mutations, inform treatment of patients as their cancer progresses, and respond to tumor development and resistance uncover interventional therapies, including immunotherapies. ”
In particular, the two companies attempted to use the biopsies to identify patients with advanced non-small cell lung cancer who could benefit from Amgen’s KRAS G12C test inhibitor sotorasib. Data from the Phase II CodeBreaK 100 study evaluating sotorasib in the study in patients with advanced non-small cell lung cancer showed that the objective response rate was comparable in patients selected with Guardant360 CDx liquid biopsy or tissue biopsy, where a high level of agreement between the two tests was demonstrated. The companies hope that Guardant360 CDx could provide clinicians with a less invasive way to test patients for this lung cancer mutation compared to a more invasive tissue sample.
France-based ImCheck presented data from an ongoing Phase I / IIa trial evaluating its anti-butyrophilin 3A (BTN3A) monoclonal antibody ICT01 in patients with relapsed / refractory solid and hematological cancer with no remaining standard of care. The ongoing results are promising. The company said the study shows that ICT01 activates γ9δ2 T cells, a subset of tumor-infiltrating lymphocytes that have potent cytotoxic effects on solid and hematological cancer cells and can trigger other immune cells to fight cancer. These data indicate that ICT01 induces a broad anti-tumor response within the tumor microenvironment.
ImChecks ICT01 is a premium humanized anti-butyrophilin 3A monoclonal antibody that selectively activates γ9δ2 T cells, which are responsible for immune surveillance for malignancy and infection.
The company said to its knowledge the data from the EVICTION study are the first demonstration of an activating antibody that safely and dose-dependently attacks γ9δ2 T cells, which also coordinate an anti-tumor immune response of the innate and adaptive immune system.