A phase IB clinical trial of<unk>  and tremelimumab showed some activity in non-small cell lung cancer (NSCLC). Phase 1 data in advanced metastatic urothelial bladder (Study 1108) has led to FDA breakthrough therapy designation. Early results of a phase I trial combining<unk>  and gefitinib in lung cancer patients "showed promise". A phase I clinical trial is currently underway using<unk>  with a TLR 7/8 agonist (MEDI 9197) for solid tumors. A Phase 1b/2a trial is underway combining<unk>  with an HPV DNA vaccine (MEDI 0457) in patients with HPV-associated recurrent/metastatic head and neck cancer. MYSTIC In July 2017, AstraZeneca announced that a phase III trial of<unk>  with tremelimumab as a first-line treatment of non-small cell lung cancer failed to meet its primary endpoint of progression-free survival. PACIFIC In November 2017, the double-blinded phase III AstraZeneca PACIFIC clinical trial demonstrated the efficacy of<unk>  in the treatment of stage III non-small cell lung cancer. 709 patients with stage III NSCLC who did not have disease progression after two or more cycles of a platinum-based chemotherapy were randomly assigned to receive<unk>  or a placebo as consolidation therapy for their lung cancer.<unk>  increased the median progression-free survival from 5.6 months (placebo) to 16.8 months<unk> ; the 12 month progression-free survival rate was increased from 35.3% (placebo) to 55.9%<unk> , and the 18 month progression-free survival rate was increased from 27.0% (placebo) to 44.2%<unk> . The median time to death or distant metastases was also increased from 14.6 months (placebo) to 23.2 months<unk> . Extreme side effects were also increased from 26.1% of patients (placebo) to 29.9% of patients<unk> . CASPIAN In March 2021, the open-label, sponsor-blind (AstraZeneca), randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide (CASPIAN) demonstrated the efficacy of<unk>  in combination with platinum-based chemotherapy in the treatment of small cell lung cancer. Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to<unk>  plus tremelimumab plus platinum–etoposide, 268 to<unk>  plus platinum–etoposide, and 269 to platinum–etoposide). As of Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3–27·9).<unk>  plus tremelimumab plus platinum–etoposide was not associated with a significant improvement in overall survival versus platinum–etoposide (hazard ratio HR 0·82 95% CI 0·68–1·00; p=0·045); median overall survival was 10·4 months (95% CI 9·6–12·0) versus 10·5 months (9·3–11·2).<unk>  plus platinum–etoposide showed sustained improvement in overall survival versus platinum–etoposide (HR 0·75 95% CI 0·62–0·91; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3–14·7) versus 10·5 months (9·3–11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 32% of 266 patients in the<unk>  plus tremelimumab plus platinum–etoposide group, 64 24% of 265 patients in the<unk>  plus platinum–etoposide group, and 88 33% of 266 patients in the platinum–etoposide group) and anaemia (34 13%, 24 9%, and 48 18%). Any-cause serious adverse events were reported in 121 (45%) patients in the<unk>  plus tremelimumab plus platinum–etoposide group, 85 (32%) in the<unk>  plus platinum–etoposide group, and 97 (36%) in the platinum–etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the<unk>  plus tremelimumab plus platinum–etoposide group (death, febrile neutropenia, and pulmonary embolism n=2 each; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death n=1 each), six (2%) patients in the<unk>  plus platinum–etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis n=1 each), and two (1%) in the platinum–etoposide group (pancytopenia and thrombocytopenia n=1 each).
Durvalumab
Evolocumab
Olaratumab
Ustekinumab
Emapalumab
Alirocumab
Tralokinumab
Dupilumab