- First results of two multi-center international Phase 1 dose-escalation and -expansion clinical trials of novel T-cell bispecific antibody cibisatamab as a single agent with or without chemotherapy, and in combination with immunotherapy atezolizumab demonstrate a safety profile consistent with each individual agent and indicate that these treatments resulted in preliminary clinical efficacy.
- First authored by Neil H. Segal, Research Director of Gastrointestinal Oncology at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, last-authored by Guillem Argilés, a Clinical Investigator at the Vall d’Hebron Institute of Oncology (VHIO) during the time of these studies, now a Senior Investigator at MSKCC, and co-authored by Josep Tabernero, Head of the Medical Oncology Department at the Vall d’Hebron University Hospital and VHIO’s Director, these data recently published as an open access article in the journal Nature Communications.
Preliminary results of two open-label Phase 1 studies of a novel T-cell bispecific antibody (TCB) cibisatamab as a single agent with or without obinutuzumab, and in combination with immunotherapy atezolizumab in patients with advanced carcinoembryonic antigen (CEA)-positive colorectal cancer have demonstrated a safety profile consistent with that of each individual agent and preliminary anti-tumor activity.
These early data, recently published open access in Nature Communications*, suggest that this treatment approach may warrant further clinical investigation toward the development of more effective immunotherapy combination strategies, particularly for patients with microsatellite stable colorectal cancer (MSS-CRC), being an ‘immune cold tumor’.
“The cancer immunotherapy revolution has led to the approval of immune checkpoint inhibitors in a diverse range of solid tumors, but these therapies lack efficacy in the majority of patients, particularly with tumor types that are characterized as nonimmunogenic, so-called ‘non-inflamed’ or ‘cold’ tumors, such as MSS-CRC,” explains co-author Josep Tabernero, Head of the Medical Oncology Department at Vall d’Hebron and VHIO’s Director.
“Optimizing immune-based strategies therefore remains a significant unmet clinical need, particularly in cancers lacking T cells infiltrating the tumor. Over recent years, T-cell bispecific antibodies have emerged as a promising antibody-based delivery system for inducing anti-tumor immunity,” adds Tabernero.
Cibisatamab is the first TCB with a 2-to-1 molecular format, optimized for safety and efficacy, directly binding CEA on tumor cells and CD3 on T cells, regardless of antigen specificity, resulting in increased T-cell infiltration, T-cell activation and tumor-cell killing. The authors of this present article*, have now described the results of two Phase 1 studies that were designed to evaluate the safety, optimal dose and schedule, and preliminary efficacy of cibisatamab as a single agent with or without obinutuzumab in the first (S1), and in combination with atezolizumab in the second (S2).
Safety and preliminary anti-tumor activity
149 and 228 patients with advanced CEA-positive solid tumors were enrolled and treated in S1 and S2, respectively. Cibisatamab-related grade ≥3 adverse events occurred in 36% of patients in S1 and in 49% of S2 patients. The overall response rate (ORR) was 4% in S1 and 7% in S2. In both studies, stable disease was observed in 27% and 35% of colorectal cancer patients, respectively.
Preliminary data of anti-tumor activity with cibisatamab monotherapy and in combination with atezolizumab indicate that these treatments resulted in clinical efficacy, with a few confirmed responses in patients with CEA-positive tumors across cohorts. In S2, patients with MSS-CRC who were given fixed doses of cibisatamab every week, every three weeks or every week in combination with atezolizumab, demonstrated a higher ORR of 14%.
“Preliminary efficacy results observed with cibisatamab in combination with atezolizumab in patients warrant further studies to extend the potential benefits of cancer immunotherapy to patients whose tumors are characterized as non-inflamed or cold,” concludes Josep Tabernero.
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