First-in-human phase 1 study of budigalimab, an anti-PD-1 inhibitor, in patients with non-small cell lung cancer and head and neck squamous cell carcinoma

Publisher Copyright: © 2021, The Author(s).Background: Budigalimab is a humanized, recombinant immunoglobulin G1 monoclonal antibody targeting programmed cell death protein 1 (PD-1). We present the safety, efficacy, pharmacokinetic (PK), and pharmacodynamic data from patients enrolled in the head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) expansion cohorts of the phase 1 first-in-human study of budigalimab monotherapy (NCT03000257; registered 15 December 2016). Patients and methods: Patients with recurrent/metastatic HNSCC or locally advanced/metastatic NSCLC naive to PD-1/PD-1-ligand inhibitors were enrolled; patients were not selected on the basis of oncogene driver mutations or PD-L1 status. Budigalimab was administered at 250 mg intravenously Q2W or 500 mg intravenously Q4W until disease progression/unacceptable toxicity. The primary endpoints were safety and PK; the secondary endpoint was efficacy. Exploratory endpoints included biomarker assessments. Results: In total, 81 patients were enrolled (HNSCC: N = 41 [PD-L1 positive: n = 19]; NSCLC: N = 40 [PD-L1 positive: n = 16]); median treatment duration was 72 days (range, 1–617) and 71 days (range, 1–490) for the HNSCC and NSCLC cohorts, respectively. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (HNSCC: n = 9, 22%; NSCLC: n = 5, 13%). Both dosing regimens had comparable drug exposure and increased interferon gamma-induced chemokines, monokine induced by gamma interferon, and interferon-gamma-inducible protein 10. Objective response rates were 13% (90% CI, 5.1–24.5) in the HNSCC cohort and 19% (90% CI, 9.2–32.6) in the NSCLC cohort. Median progression-free survival was 3.6 months (95% CI, 1.7–4.7) and 1.9 months (95% CI, 1.7–3.7) in the HNSCC and NSCLC cohorts. Conclusions: The safety, efficacy and biomarker profiles of budigalimab are similar to other PD-1 inhibitors. Development of budigalimab in combination with novel anticancer agents is ongoing.Peer reviewe

Local treatment of a pleural mesothelioma tumor with ONCOS-102 induces a systemic antitumor CD8(+) T-cell response, prominent infiltration of CD8(+) lymphocytes and Th1 type polarization

Peer reviewe

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study

PURPOSE: Pembrolizumab has previously shown antitumor activity against programmed death ligand 1 (PD-L1)-positive metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed the antitumor activity and safety of pembrolizumab in three parallel cohorts of a larger mCRPC population. METHODS: The phase II KEYNOTE-199 study included three cohorts of patients with mCRPC treated with docetaxel and one or more targeted endocrine therapies. Cohorts 1 and 2 enrolled patients with RECIST-measurable PD-L1-positive and PD-L1-negative disease, respectively. Cohort 3 enrolled patients with bone-predominant disease, regardless of PD-L1 expression. All patients received pembrolizumab 200 mg every 3 weeks for up to 35 cycles. The primary end point was objective response rate per RECIST v1.1 assessed by central review in cohorts 1 and 2. Secondary end points included disease control rate, duration of response, overall survival (OS), and safety. RESULTS: Two hundred fifty-eight patients were enrolled: 133 in cohort 1, 66 in cohort 2, and 59 in cohort 3. Objective response rate was 5% (95% CI, 2% to 11%) in cohort 1 and 3% (95% CI, = 21.8 months) and 10.6 months (range, 4.4 to 16.8 months), respectively. Disease control rate was 10% in cohort 1, 9% in cohort 2, and 22% in cohort 3. Median OS was 9.5 months in cohort 1, 7.9 months in cohort 2, and 14.1 months in cohort 3. Treatment-related adverse events occurred in 60% of patients, were of grade 3 to 5 severity in 15%, and led to discontinuation of treatment in 5%. CONCLUSION: Pembrolizumab monotherapy shows antitumor activity with an acceptable safety profile in a subset of patients with RECIST-measurable and bone-predominant mCRPC previously treated with docetaxel and targeted endocrine therapy. Observed responses seem to be durable, and OS estimates are encouraging

Gene expression analysis of tumors demonstrates an induction of Th1 type immune response following intratumoral administration of ONCOS-102 in refractory solid tumor patients

2014-11-0

Phase I study with ONCOS-102 for the treatment of solid tumors - an evaluation of clinical response and exploratory analyses of immune markers

Peer reviewe

Diagnostinen ongelmatapaus : ihomuutokset ja etenevät keskushermosto-oireet lymfooman ilmentyminä

Non peer reviewe

Follow-up of cancer patients receiving anti-PD-(L)1 therapy using an electronic patient-reported outcomes tool (KISS):prospective feasibility cohort study

Abstract Background: Immune checkpoint inhibitors (ICIs) have become a standard of care for various tumor types. Their unique spectrum of side effects demands continuous and long-lasting assessment of symptoms. Electronic patient-reported outcome (ePRO) follow-up has been shown to improve survival and quality of life of cancer patients treated with chemotherapy. Objective: This study aimed to investigate whether ePRO follow-up of cancer patients treated with ICIs is feasible. The study analyzed (1) the variety of patient reported symptoms, (2) etiology of alerts, (3) symptom correlations, and (4) patient compliance. Methods: In this prospective, one-arm, multi-institutional study, we recruited adult cancer patients whose advanced cancer was treated with anti-programmed cell death protein 1 (PD)- ligand (L)1 agents in outpatient settings. The ePRO tool consisted of a weekly questionnaire evaluating the presence of typical side effects, with an algorithm assessing the severity of the symptom according to National Cancer Institute Common Terminology Criteria for Adverse Events and an urgency algorithm sending alerts to the care team. A patient experience survey was conducted monthly. The patients were followed up to 6 months or until disease progression. Results: A total of 889 symptom questionnaires was completed by 37 patients (lung cancer, n=15; melanoma, n=9; genitourinary cancer, n=9; head and neck cancer, n=4). Patients showed good adherence to ePRO follow-up. The most common grade 1 symptoms were fatigue (28%) and itching (13%), grade 2 symptoms were loss of appetite (12%) and nausea (12%), and grade 3-4 symptoms were cough (6%) and loss of appetite (4%). The most common reasons for alerts were loss of appetite and shortness of breath. In the treatment benefit analysis, positive correlations were seen between clinical benefit and itching as well as progressive disease and chest pain. Conclusions: According to the results, ePRO follow-up of cancer patients receiving ICIs is feasible. ePROs capture a wide range of symptoms. Some symptoms correlate to treatment benefit, suggesting that individual prediction models could be generated. Trial Registration: Clinical Trials Register, NCT3928938; https://clinicaltrials.gov/ct2/show/NCT0392893