T-cell therapy trial fails to meet primary efficacy endpoint for refractory NSCLC
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A gamma-delta T-cell therapy failed to significantly prolong PFS for patients with treatment-refractory non-small cell lung cancer, according to study results presented at American Association for Cancer Research Virtual Annual Meeting II.
Despite its limited clinical efficacy, the autologous cell therapy showed antitumor activity with an acceptable safety profile. Consequently, it may be a candidate for use as part of combination therapy for refractory NSCLC, according to the researchers.
“Not all patients with non-small cell lung cancer possess drug-targetable driver mutations, and response rates to immune checkpoint blockade therapies remain unsatisfactory,” Kazuhiro Kakimi, MD, PhD, professor in the department of immunotherapeutics at University of Tokyo Hospital, said during a presentation. “More effective treatments are needed.”
Kakimi and colleagues conducted a phase 2, multicenter, open-label, single-arm trial of an adoptive cell therapy that used zoledronate-expanded autologous gamma-delta T cells for adults with treatment-refractory NSCLC.
The circulating gamma-delta T cells target tumor cells via metabolic or other abnormalities, Kakimi said. A phase 1 study showed the investigational autologous therapy is safe.
The phase 2 study included 25 patients with NSCLC (median age 66 years; range, 33-86; 56% men; 100% Asian) who had received at least two standard chemotherapy regimens for unresectable disease or at least one treatment regimen or radiation for recurrent disease after surgery. Twenty patients had adenocarcinoma, four had squamous cell carcinoma and one had large cell carcinoma.
Patients underwent leukapheresis to collect their mononuclear cells. These cells then were cultured with zoledronic acid and interleukin-2 and expanded to greater than 1 × 109 autologous gamma-delta T cells. Patients received an IV infusion of the expanded gamma-delta cells every 2 weeks for a total of six infusions. Those who perceived clinical benefit could receive additional infusions until disease progression.
PFS served as the study’s primary endpoint; researchers considered the treatment to have clinical efficacy if median PFS significantly exceeded 3 months.
Secondary endpoints included OS, best objective response rate, disease control rate and safety.
Sixteen patients completed all six infusions.
Efficacy results showed median PFS of 95 days (95% CI, 73-132), with a 3-month PFS rate of 50.2% (95% CI, 32.6-65.4).
“This did achieve the predefined threshold PFS of 3 months but failed to achieve the expected PFS of 4 months,” Kakimi said. “Therefore, we must conclude that we failed to demonstrate the efficacy of adoptive autologous gamma-delta T-cell immunotherapy for treatment-refractory NSCLC, at least according to this criterion.”
Median OS was 418 days (95% CI, 179-479), with a 3-month OS rate of 96% (95% CI, 80.9-99.2). Best overall responses included one partial response and 16 patients with stable disease, four of whom remained progression-free for longer than 6 months. Eight patients (32%) had progressive disease.
The ORR was 4% (95% CI, 0.1-20.4), with a disease control rate of 68% (95% CI, 46.5-85.1%).
Safety results showed 19 patients (76%) experienced adverse events, including 12 patients (48%) with grade 3 or greater events. The most frequent adverse events included cough (28% any grade, 16% grade 3), dyspnea (24% any grade, 4% grade 3) and anorexia (28% any grade, 12% grade 3). Nearly a quarter of patients (24%) developed an infection.
Investigators attributed most adverse events to disease progression, except for one case of pneumonitis that was considered related to the gamma-delta T-cell therapy.
“Although autologous gamma-delta T-cell therapy was well-tolerated and may have an acceptable disease control rate, this trial did not meet its primary efficacy endpoint,” Kakimi said. “However, considering their unique mechanism of action against tumor cells, gamma-delta T cells may be valuable candidates as components of combination therapies for treatment-refractory non-small cell lung cancer.”
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Kakimi K, et al. Abstract 1069. Presented at: American Association for Cancer Research Virtual Annual Meeting II; June 22-24, 2020.
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