This is a randomized, double-blind, multi-center, global Phase II study to determine the efficacy and safety of Durvalumab plus Olaparib combination therapy compared with Durvalumab monotherapy as maintenance therapy in patients whose disease has not progressed following Standard of Care (SoC) platinum-based chemotherapy with Durvalumab as first-line treatment in patients with Stage IV non small-cell lung cancer (NSCLC) with tumors that lack activating epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions.

This is a Phase II, international, open-label, two-arm, non-randomised study of AZD4635 in participants with metastatic castration-resistant prostate cancer (mCRPC).

Sometimes, cancer patients receive an initial treatment, followed by additional treatment to lower the chance of cancer coming back. The standard or usual treatment for this type of disease is initially having radiation therapy at the same time as chemotherapy (with a drug called cisplatin), with no additional therapy afterwards

BACKGROUND: The combination of durvalumab and tremelimumab results in clinical benefit, with a tolerable safety profile in patients with solid tumors. OBJECTIVE: To evaluate the efficacy and safety of durvalumab in combination with tremelimumab compared with either drug alone. METHODS: The online databases (PubMed, Web of Science, EMBASE, and Cochrane Library) were searched for potential clinical studies up to Nov 26, 2019. Eligible studies were prospective and registered clinical trials. Pooled odds ratios for objective response rate and disease control rate and pooled risk ratios for treatment-related adverse events were meta-analyzed. A random-effect model was used due to the synthesis of different cancer types. RESULTS: Overall, 5 studies were eligible for systematic review, 3 of which were further meta-analyzed. Durvalumab plus tremelimumab was superior to tremelimumab monotherapy in improving disease control rate in head and neck squamous cell carcinoma. However, there were no significant differences between dual immunotherapy and mono-immunotherapy in pancreatic ductal adenocarcinoma and gastric and gastroesophageal junction adenocarcinoma. Additionally, pooled analyses illustrated that no significant differences in treatment-related adverse events were displayed between the 2 groups. CONCLUSION: Durvalumab and tremelimumab combination therapy had a good safety profile and resulted in clinical benefit in head and neck squamous cell carcinoma. Future explorations are needed to further confirm the application of durvalumab plus tremelimumab.

BACKGROUND: Recently, the combination of durvalumab and tremelimumab, two immune checkpoint inhibitors, for the treatment of different types of cancers has been considered; however, its overall effects, including its safety, are still unclear and need to be further investigated. OBJECTIVES: The aim of the present systematic review and meta-analysis was to investigate the safety and tolerability of this combination of drugs. METHODS: A systematic review of the literature, based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, was conducted by employing online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. The selection of eligible publications was made following a staged screening and selection process. The software RevMan 5.4 was used to run the quantitative analysis and forest plots, while the Cochrane tool was employed for risk of bias assessment. RESULTS: From the retrieved 157 results, 9 randomized controlled trials involving 3060 patients were included. By comparing the combination of durvalumab and tremelimumab vs. durvalumab monotherapy, it was observed that: adverse events (AEs) ≥ Grade 3 incidence was 32.6% (536/1646) vs. 23.8% (336/1414) (Z = 2.80; p = 0.005; risk ratio (RR) = 1.44), reduced appetite incidence was 10.8% (154/1427) vs. 8.3% (108/1305) (Z = 2.26; p = 0.02; RR = 1.31), diarrhea was reported in 15.6% (229/1473) vs. 8.1% (110/1352) (Z = 5.90; p < 0.00001; RR = 1.91), rash incidence was equal to 11.1% (160/1441) vs. 6.5% (86/1320) (Z = 4.35; p <0.0001; RR = 1.75), pruritis was 13.6% (201/1473) vs. 7.7% (104/1352) (Z = 5.35; p < 0.00001; RR = 1.83), fever was 10.5% (42/399) vs. 6.6% (22/330) (Z = 2.27; p = 0.02; RR = 1.77), discontinuation rate was 18% (91/504) vs. 3% (36/434) (Z = 4.78; p < 0.00001; RR = 2.41), and death rate was 2.6% (13/504) vs. 0.7% (3/434) (Z = 1.90; p = 0.06; RR = 2.77). CONCLUSIONS: It was observed that the combined (durvalumab and tremelimumab) vs. monotherapy (durvalumab) is associated with a higher risk of treatment discontinuation, mortality, fever, diarrhea, rash, pruritis, and reduced appetite. This information is relevant and should be disclosed, especially to patients that are currently enrolled in clinical trials considering this combined therapy.

The proposal is a phase II clinical study designed to assess the feasibility of durvalumab (MEDI4736) in HIV-1-infected individuals with solid tumors. Additionally, to obtain data that lets understand the possible benefit of this treatment in cancer patients and HIV infection, exploring if activity of durvalumab (MEDI4736) could be higher in cancer that has been produced at least in part due to the chronic immunosupression. Simultaneously, it will allow us to investigate the effect of disrupting this immunoregulatory pathway might have in reversing cancer pathways and HIV-specific T-cell function during persistent chronic HIV infection in humans.

A Global Study to Determine the Efficacy and Safety of Durvalumab in Combination with Gemcitabine+Cisplatin for Neoadjuvant Treatment and Durvalumab Alone for Adjuvant Treatment in Patients with Muscle-Invasive Bladder Cancer

This is a randomized multi-arm trial evaluating the safety and efficacy of thoracic radiation therapy followed by either durvalumab as monotherapy or in combination with tremelimumab or olaparib in participants with Extensive-Stage Disease Small Cell Lung Cancer (ES-SCLC) who have completed a first-line platinum-based chemotherapy regimen and achieved ongoing complete response (CR), partial response (PR) or stable disease (SD).

BACKGROUND: PD-1/PD-L1 inhibitors (PDx) improve survival in 2L NSCLC, primarily in PD-L1 high pts. Combining PDx with CTLA-4 agents may address unmet medical needs by providing synergistic antitumor activity even in PD-L1 low/neg pts in this setting. This Phase 3 trial (NCT02352948) evaluated durvalumab (D) vs SoC and D plus anti-CTLA-4 tremelimumab (T) vs SoC in Stage IIIB/IV NSCLC. METHODS: Eligible pts had 2 prior systemic treatments (1 platinum-based CT), WHO PS 0/1, no prior PDx and were EGFR/ALK WT. From Q2 2015, in sub study A (SSA), PD-L1 TC 25% (Ventana SP263 assay) pts were randomized 1:1 to D 10 mg/kg IV q2w for up to 12 mo or SoC (erlotinib 150 mg QD PO, gemcitabine 1000 mg/m2 IV [day 1, 8, and 15 of a 28-day cycle] or vinorelbine 30 mg/m2 IV [day 1, 8, 15, and 22 of a 28-day cycle]). In sub study B (SSB), PD-L1 TC <25% pts were randomized 3:2:2:1 to DþT (D 20 mg/kg IV þ T 1 mg/kg IV q4w for up to 12 wks then D 10 mg/kg IV q2w for 34 wks); SoC (as SSA); D (as SSA); or T 10 mg/kg IV q4w for 24 wks then q12w for 24 wks. Co-primary endpoints were OS and PFS for DþT vs SoC in SSB and D vs SoC in SSA. Secondary endpoints included 12-mo OS and PFS, ORR, safety and QoL. All 5% alpha was given to SSB (4% OS; 1% PFS); SSA was descriptive with no statistical testing. RESULTS: Due to recruitment challenges 126/250 (SSA) and 469/600 (SSB) planned pts were randomized (DCO Feb 09 2018). Baseline characteristics were well balanced. In SSB, median OS was 11.5 vs 8.7 mo with DþT vs SoC (HR 0.80 [95% CI 0.61, 1.05]; p ¼ 0.109). 12-mo OS rates were 49.5% and 38.8%. Median PFS was 3.5 vs 3.5 mo (HR 0.77 [0.59, 1.01]; p ¼ 0.056) with 12-mo PFS rates of 20.6% and 8.0%. ORR was 14.9% DþT and 6.8% SoC. In SSA, median OS was 11.7 vs 6.8 mo with D vs SoC (HR 0.63 [0.42, 0.93]). 12-mo OS rates were 49.3% and 31.3%. Median PFS was 3.8 vs 2.2 mo (HR 0.71 [0.49, 1.04]) with 12-mo PFS rates of 19.4% and 9.9%. ORR was 35.5% D and 12.5% SoC. Grade 3 treatment-emergent AEs were 46.8% DþT and 54.5% SoC in SSB; 45.2% D and 66.7% SoC in SSA. CONCLUSIONS: In the 3L setting, D monotherapy provided a clinically meaningful improvement in OS vs SoC in PD-L1 TC 25% pts. DþT did not significantly improve OS or PFS vs SoC in PD-L1 TC <25% pts. DþT, D and T exhibited manageable safety profiles. Further biomarker analyses may help identify pts who may benefit most from DþT, D or T in advanced NSCLC.

This is a multicenter, open-label, stratified, randomized study to evaluate the safety, tolerability, antitumor activity, pharmacokinetics, pharmacodynamics, and immunogenicity of durvalumab or tremelimumab monotherapy, or durvalumab in combination with tremelimumab or bevacizumab in advanced hepatocellular carcinoma.