Table 4.

FDA benefit: risk analysis.

Dimension	Evidence and uncertainties	Conclusions and reasons
Analysis of Condition	HCC and intrahepatic bile duct cancer accounts for 2.2% of all new cancers in the United States and the 5-year relative survival is 12.8% for locoregional disease and 3.1% for metastatic disease.	Unresectable HCC is a serious and life-threatening condition with a poor prognosis.
Current treatment options	FDA approved therapies for the first line treatment of unresectable HCC include: atezolizumab plus bevacizumab, sorafenib, and lenvatinib. However, not all patients are eligible to receive bevacizumab and there are significant toxicities associated with tyrosine kinase inhibitors.	There is an unmet medical need for new effective treatments for patients with unresectable HCC
Benefit	In the HIMALAYA trial, tremelimumab in combination with durvalumab demonstrated a statistically significant and clinically meaningful improvement in OS compared to sorafenib (stratified HR of 0.78 [95% CI: 0.66, 0.92], stratified log-rank 2-sided p-value =0.0035).	The study met its primary objective with T300+D demonstrating superiority in OS over sorafenib and the statistically significant effect on OS is clinically meaningful.
Risk and risk management	The most common adverse reactions (≥20%) were rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain.	The observed safety profile is acceptable when assessed in the context of the treatment of a life-threatening disease. Most of the adverse reactions were manageable with dosage modifications. The risks of severe and serious adverse reactions, such as immune mediated reactions, are adequately addressed in the Warnings and Precautions and Dosage Modifications sections of the product labeling.

Source: U.S. Food and Drug Administration. BLA Multidisciplinary Review and Evaluation and Approval Package: IMJUDO (tremelimumab) (9).