KEY TAKEAWAYS
- The COBALT-RCC Phase 1 trial investigated the efficacy of allogeneic CAR T-cell therapy targeting CD70 in patients.
- The study’s primary aim was to assess the safety and efficacy of CTX130™, an allogeneic CAR T cell therapy targeting CD70, in patients with advanced ccRCC.
- The subjects underwent conventional lymphodepleting chemotherapy comprising fludarabine and cyclophosphamide for three days.
- The study demonstrated a favorable safety profile of CTX130 with promising antitumor activity. The overall disease control rate was 76.9%.
- No dose-limiting toxicities were observed across all dose levels, but three patients encountered significant unfavorable occurrences associated with CRS.
- The study results demonstrated the feasibility of utilizing CD70-targeted CAR T cells in treating ccRCC and other malignancies exhibiting CD70 expression.
The most prevalent form of renal tumor is clear cell renal cell carcinoma (ccRCC). The prognosis of individuals with clear cell renal cell carcinoma (ccRCC) who do not respond to checkpoint inhibitors (CPIs) and tyrosine kinase inhibitors (TKIs) is unfavorable. CD70 was significantly expressed in ccRCC tumor specimens during preclinical investigations. This study presented findings from the Phase 1 dose-escalation trial of CTX130™, an allogeneic CAR T cell therapy targeting CD70, administered to patients diagnosed with ccRCC. The COBALT-RCC (NCT04438083) phase 1, open-label, a multicenter, global investigation aimed to assess the safety and efficacy of CTX130 in patients who are 18 years or older and have advanced (unresectable or metastatic), relapsed, or refractory (R/R) clear cell renal cell carcinoma (ccRCC) and have previously been exposed to both CPIs and TKIs. The subjects underwent conventional lymphodepleting chemotherapy comprising fludarabine 30mg/m2 and cyclophosphamide 500mg/m2 for three days, after which they were administered CTX130 infusion. Till May 2, 2022, CTX130 was administered to 14 patients with a median age of 64.5 years (range 54-77). All the patients presented with stage IV disease and underwent a median of 3 (range, 1-6) previous treatments.
At the time of the study initiation, six patients had a documented condition that was unresponsive to treatment. The median expression level of CD70 on the tumors was 100%, with a 1-100% range. The administered CTX130 was dosed at various levels, ranging from 3×107 to 9×108 CAR T cells, in the patients. In general, there was an expansion observed in all the DLs. A correlation between increased CAR T exposure and improved disease control has been observed. CTX130 exhibited a satisfactory safety profile, with no dose-limiting toxicities observed across all dose levels. Seven patients (50%) exhibited grade 1-2 cytokine release syndrome (CRS), while no patients experienced CRS of grade 3 or higher. Three patients have encountered significant unfavorable occurrences (SAEs) associated with CTX130, all of which were instances of cytokine release syndrome (CRS). Three patients experienced serious adverse events (SAEs) related to infections, which were not associated with CTX130. These included a Grade 5 pneumonia with Grade 4 dyspnea that led to the patient’s demise. There were no reported cases of immune effector cell-associated neurotoxicity syndrome, graft versus host disease, or hemophagocytic lymphohistiocytosis among the patients. One individual (7.7%) exhibited a persistent complete remission (CR) sustained for 18+ months. Additionally, 9 patients (69.2%) displayed stable disease (SD), with 4 of these patients (30.8%) maintaining SD at the 4-month mark.
The overall disease control rate, including complete response, partial response, and stable disease, was 76.9%. The initial clinical trial investigating the efficacy of CD70 CAR T-cell therapy in ccRCC demonstrated a favorable safety profile with no unforeseen on-target off-tumor toxicities and promising antitumor activity. Per our understanding, attaining this resilient complete response (CR) is a pioneering feat in the use of allogeneic CAR T cell therapy for patients with relapsed or refractory (R/R) solid tumors. This accomplishment demonstrates the feasibility of utilizing CD70-targeted CAR T cells in the treatment of clear cell renal cell carcinoma (ccRCC) and other malignancies that exhibit CD70 expression. Further investigation in this area is warranted.
Source:https://jitc.bmj.com/content/10/Suppl_2/A584
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04438083
Sumanta Pal, Ben Tran, John Haanen, Michael Hurwitz, Adrian Sacher, Neeraj Agarwal, Nizar Tannir, Elizabeth Budde, Simon Harrison, Sebastian Klobuch, Sagar Patel, Mary Lee Dequeant, Verena Karsten, Kaitlyn Cohen, Ellen Gurary, Henia Dar, Anna Ma, Anjali Sharma and Samer Srour/558 CTX130 allogeneic CRISPR-Cas9–engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: Results from the phase 1 COBALT-RCC study/Journal for ImmunoTherapy of Cancer, 10(Suppl 2). https://doi.org/10.1136/jitc-2022-SITC2022.0558
