PL02.01 Durvalumab ± Tremelimumab + Chemotherapy as First-line Treatment for mNSCLC: Results from the Phase 3 POSEIDON Study
Melissa L. JohnsonByoung Chul ChoAlexander LuftJorge Alatorre-AlexanderSarayut Lucien GeaterК. К. ЛактионовAleksei VasilievDmytro TrukhinSujeong KimG. UrsolMaen HusseinF. LimChun YangLuiz H. AraujoHaruhiro SaitoNiels ReinmuthXiaoshun ShiL. PooleSolange PetersEdward B. GaronTony Mok
50
Citation
0
Reference
10
Related Paper
Citation Trend
Keywords:
Tremelimumab
Durvalumab
Nimotuzumab
Tremelimumab
Durvalumab
Nimotuzumab
Cite
Citations (50)
Tumor immunotherapy is an important clinical strategy for the treatment of various solid and hematological malignancies, and its use is on the rise. Immune checkpoint inhibitors (ICIs) are immunotherapies that boost anticancer immune responses by targeting receptors on the surface of T-lymphocytes. Two important ICIs are anti-programmed death ligand-1 (anti-PD-L1) monoclonal antibodies and anti-cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) monoclonal antibodies. Tremelimumab (anti-CTLA-4) and durvalumab (anti-PD-L1) have been shown to be effective monotherapies. However, their combination has demonstrated effective and encouraging antitumor activity with manageable safety in patients with unresectable hepatocellular carcinoma. We present the case of an 80-year-old male with hepatocellular carcinoma who had undergone drug-eluting bead transarterial chemoembolization (DEB-TACE) on three occasions and had been started on a combination of ICIs, durvalumab, and tremelimumab. He subsequently developed various immune-related adverse effects in different organ systems, including hepatic and cardiovascular complications. Appropriate treatment was administered, but ultimately, he passed away. We aim to discuss the initial evaluation for suspected immune-related adverse events, specifically those related to myocarditis and its various manifestations, prognosis, and treatment.
Tremelimumab
Durvalumab
CTLA-4
Cite
Citations (2)
Meeting abstracts As single agents, durvalumab (MEDI4736), a human IgG1 anti-PD-L1 antibody, and tremelimumab, a human IgG2 anti-CTLA-4 antibody, have shown acceptable safety profiles and antitumor activity. Similar to other anti-PD-L1/anti-PD-1 monotherapies, durvalumab has shown greater objective
Durvalumab
Tremelimumab
Cite
Citations (16)
Advances in immunotherapy have led to radical improvements in outcomes, including overall survival, such as in non-small cell lung cancer (NSCLC) patients with metastatic disease treated with immune checkpoint inhibitors. More recently, promising results have been obtained in earlier disease settings, and combinations with other therapies are being actively investigated. Durvalumab, a monoclonal antibody directed against the programmed death ligand 1, has demonstrated significant activity in NSCLC, including increased progression-free survival rates after chemoradiation for unresectable stage III disease, with a favourable safety profile. Clinical trials, including phase III studies, are ongoing as monotherapy and in combination with chemotherapy, radiotherapy and other immunotherapies, such as the anti-cytotoxic T-lymphocyte antigen 4 drug tremelimumab, in diverse stages of the disease.
Durvalumab
Tremelimumab
Avelumab
Cite
Citations (24)
On October 21, 2022, the FDA approved tremelimumab (Imjudo) in combination with durvalumab for adult patients with unresectable hepatocellular carcinoma. The approval was based on the results from the HIMALAYA study, in which patients with unresectable hepatocellular carcinoma who were naïve to previous systemic treatment were randomly assigned to receive one of three study arms: tremelimumab in combination with durvalumab (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The primary objective of improvement in overall survival (OS) for tremelimumab in combination with durvalumab compared with sorafenib met statistical significance with a stratified HR of 0.78 [95% confidence interval (CI), 0.66-0.92; P = 0.0035]. The median OS was 16.4 months (95% CI, 14.2-19.6) with tremelimumab in combination with durvalumab and 13.8 months (95% CI, 12.3-16.1) with sorafenib. Adverse reactions occurring in ≥20% of patients receiving tremelimumab in combination with durvalumab were rash, fatigue, diarrhea, pruritus, musculoskeletal pain, and abdominal pain. The recommended tremelimumab dose for patients weighing 30 kg or more is 300 mg, i.v., as a single dose in combination with durvalumab 1,500 mg at cycle 1/day 1, followed by durvalumab 1,500 mg, i.v., every 4 weeks. For those weighing less than 30 kg, the recommended tremelimumab dose is 4 mg/kg, i.v., as a single dose in combination with durvalumab 20 mg/kg, i.v., followed by durvalumab 20 mg/kg, i.v., every 4 weeks.
Durvalumab
Tremelimumab
Cite
Citations (25)
8558 Background: The anti-CTLA-4 tremelimumab at two different dose-schedules of administration showed promising activity in second-line malignant mesothelioma (MM) patients (Calabrò et al., Lancet Oncol, 2013; Calabrò et al., Lancet Respir Med, 2015). These initial results and the efficacy of targeting the PD-1/PD-L1 axis in different tumor types, prompted the NIBIT-MESO-1 study aimed at investigating the efficacy and safety of tremelimumab combined with the anti-PD-L1 durvalumab in mm patients. We report the safety analysis from the fully-enrolled NIBIT-MESO-1 study. Methods: The NIBIT-MESO-1 is a phase II, open-label, single Center study. Forty mm patients received tremelimumab at 1 mg/Kg i.v. every 4 weeks (Q4W) for 4 doses, and durvalumab at 20 mg/Kg i.v. Q4W for 13 doses. Primary objective is immune-related (ir)-objective response rate; secondary are safey, ir-disease control rate, ir-progression free survival, and overall survival. Tumor assessment per ir-modified RECIST or ir-RECIST 1.1 for pleural or peritoneal MM, respectively, was performed at baseline and q12 weeks. Adverse events (AEs) were recorded according to CTC v4.0. (ClinicalTrials.gov Id: NCT02588131). Results: From October 2015 to October 2016, 40 mm patients (38 pleural and 2 peritoneal), median age 64 years (range 41-80), ECOG performance status 0 (n = 19) or 1 (n = 21) were enrolled in the study. mm histology was epithelioid (n = 32), biphasic (n = 5), sarcomatoid (n = 2) or undefined (n = 1). As of January 2017, 12 first or 28 second-line mm patients received a median of 5.5 doses of therapy (range = 1-13). Twenty-four patients (60%) experienced any grade irAEs: 5 patients (12.5%) had grade 3-4 AEs, the most frequent being hepatotoxicity (7.5%). AEs were generally manageable and reversible per protocol guidelines. Three patients (7.5%) were discontinued due to treatment-related AEs (1 trombocytopenia, 1 limbic encephalitis, 1 liver toxicity). Conclusions: The combination of tremelimumab and durvalumab is safe and manageable in mm patients. Clinical trial information: NCT02588131.
Durvalumab
Tremelimumab
Clinical endpoint
Cite
Citations (8)
Tremelimumab
Durvalumab
Cite
Citations (0)
Tremelimumab
Durvalumab
Regimen
Tolerability
Cite
Citations (11)
4031 Background: The combination of durvalumab (D; anti–PD-L1) and tremelimumab (T; anti–CTLA-4) has the potential to amplify T-cell responses against tumors through immune checkpoint blockade, resulting in antitumor activity. Methods: This is an ongoing Phase Ib/II study in patients (pts) with metastatic or recurrent gastric or gastroesophageal junction carcinoma. An initial safety run-in was conducted in 6 pts who received D 20 mg/kg and T 1 mg/kg IV Q4W for 4 cycles followed by D 10 mg/kg Q2W for ≤12 mo. For Phase II expansion, all pts were immunotherapy naive and had progressed after systemic platinum- or fluoropyrimidine-based chemotherapy. Second-line (2L) pts were randomized 2:2:1 to D+T, D 10 mg/kg Q2W up to 12 mo, or T 10 mg/kg Q4W for 7 doses then Q12W for 2 doses. Third-line (3L) pts received D+T. Tumor cell PD-L1 expression was assessed by IHC (Ventana SP263). Results: As of Sept 13, 2017, 58 pts received D+T (35% PD-L1 > 1%), 24 pts received D (38% PD-L1 > 1%), and 12 pts received T (50% PD-L1 > 1%); median duration of follow-up was 9.2, 3.5, and 9.2 mo, respectively. Drug-related grade 3/4 adverse events (AEs) occurred in 17 pts (29%) who received D+T; most frequent was colitis (5%). Six (50%) and 4 (17%) pts had grade 3/4 AEs related to T or D alone, respectively. Ten pts (17%) who received D+T discontinued due to drug-related AEs; most frequent was colitis (5%). One pt (4%) with D and 4 pts (33%) with T discontinued due to drug-related AEs. There were no drug-related deaths. In the T cohort, 1 pt (8%) had a confirmed PR; progression-free survival (PFS) and overall survival (OS) rates are not presented due to small sample size. Clinical activity in the other cohorts is shown below. Conclusions: D+T has a manageable safety profile in 2L and 3L advanced gastric cancer, with encouraging OS versus D monotherapy. Clinical trial information: NCT02340975. 2L D+T n = 27 3L D+T n = 25 2L D n = 24 Confirmed + unconfirmed ORR, n (%) 95% CI 3 (11.1) 2.4‒30.2 3 (12.0) 3.0‒36.3 2 (8.3) 1.5‒36.4 DCR—8 wk, n (%) 95% CI 12 (44.4) 25.5–64.7 11 (44.0) 24.4–65.1 3 (12.5) 2.7–32.4 Median PFS (95% CI), mo 1.8 (1.6–3.3) 1.8 (1.6–3.5) 1.6 (1.0–1.8) Median OS (95% CI), mo 9.2 (4.2–12.8) 10.6 (4.8–17.0) 3.2 (1.7–4.4)
Durvalumab
Tremelimumab
Cite
Citations (13)
Cancer immunotherapy represents one of the most important innovations in modern medicine. Durvalumab is an anti-programmed cell death ligand 1 (PDL-1) agent which is currently under investigation in several studies in combination with the anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) drug tremelimumab. The aim of this review was to systematically identify and revise the current scientific literature investigating the combination of these two drugs in solid tumors. A digital search on the Medline (PubMed interface) and Scopus databases for articles published from inception to 26 February 2021 was performed. The terms used for the search were durvalumab AND tremelimumab. Trials reported in English involving adult patients with solid cancers treated with the combination durvalumab plus tremelimumab were retrieved; the references of the articles were cross-checked to identify missing papers. The electronic search produced 267 results; after exclusion of duplicates, irrelevant articles, reviews, and papers not in English or missing data, 19 articles were included for revision. The total number of patients treated with the combination of durvalumab and tremelimumab in the studies retrieved was 2052. The combination of durvalumab plus tremelimumab showed some oncological advantages in comparison with traditional chemotherapies in some subsets of tumors, but generally has not shown consistent advantages in comparison with the employment of durvalumab monotherapy. A number of the studies examined had intrinsic methodological limitations; therefore, future well-designed studies involving larger cohorts are warranted.
Tremelimumab
Durvalumab
Cite
Citations (17)