medwireNews: Vibostolimab given alone or in combination with pembrolizumab is well tolerated and demonstrates antitumor activity in patients with advanced solid tumors, including non-small-cell lung cancer (NSCLC), show results of a first-in-human study of the antibody targeting the T cell immunoglobulin and immunoreceptor tyrosine-based inhibition (TIGIT) domain.
“[O]ur data provide promising antitumor activity in patients with advanced solid tumors and PD-1/PD-L1-inhibitor-naïve patients with advanced solid tumors treated with vibostolimab plus pembrolizumab, and they support further investigation of the treatment combination,” say Jiaxin Niu (Banner MD Anderson Cancer Center, Gilbert, Arizona, USA) and colleagues.
The phase 1 study was spilt into two parts. For the first part, 76 patients with metastatic solid tumors were randomly assigned to receive vibostolimab, at escalating doses ranging from 2.1–700.0 mg, alone (n=34) or in combination with pembrolizumab 200 mg (n=42), every 3 weeks.
During a median follow-up of 34 months, over half of the patients in the monotherapy and combination arms had a treatment-related adverse event (TRAE; 56% and 62%, respectively).
Among the vibostolimab monotherapy group, three patients had grade 3–4 TRAEs, with macropapular rash, anemia, and diarrhea each reported in one patient. In addition, TRAEs of grade 3–4 occurred in seven patients in the combination treatment group, including single incidences of macropapular rash, adrenal insufficiency, and increased alanine aminotransferase. There were no treatment-related deaths in either group.
The confirmed objective response rate (ORR) in this solid tumor group was 0% with vibostolimab monotherapy and 7% with the combination.
The second (expansion) part of the study included 67 patients with anti-PD-1/PD-L1-refractory NSCLC who received vibostolimab 200 mg alone (n=34) or with pembrolizumab 200 mg (n=33) and an additional 39 patients with anti-PD-1/PD-L1-naïve NSCLC who received the combination. Median follow-up was 24 months.
Grade 3 to 5 TRAEs were seen in five patients each in the anti-PD-1/PD-L1-refractory patients given monotherapy and combination treatment. In the monotherapy arm, there was one grade 3–5 TRAE each of increased lipase, rash, colitis, hyperlipasemia, and macular rash, while in the combination group there were two cases of hypertension and one case each of increased lipase, dyspnea, back pain, depression, fatigue, musculoskeletal pain, and pneumonitis.
In the anti-PD-1/PD-L1-naïve group, six had a grade 3–5 TRAE, specifically three patients had decreased lymphocyte count, and one patient each had hypotension, rash, erosive duodenitis, gastrointestinal reflux disease, and hyponatremia.
The study authors say the antitumor activity of the vibostolimab combination was “promising” in the anti-PD-1/PD-L1-naïve group, with a confirmed ORR of 26%, but “modest” in the anti-PD-1/PD-L1-refractory patient group, with ORRs of 3% in both the monotherapy and combination arms.
Acknowledging the study has a small study population and is underpowered for statistical validation, the team says the results should be “interpreted with caution.”
The authors observe that “the evaluation of a small population of patients with PD-1/PD-L1-inhiibtor-refractory disease was exploratory and did not provide insight into whether resistance was primary or acquired.”
Nevertheless, they conclude in the Annals of Oncology that their findings “support further investigation of the treatment combination” in the ongoing studies of NSCLC and other advanced solid tumors.
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