AstraZeneca PLC announced positive high-level results from the NIAGARA Phase III trial showed AstraZeneca?s IMFINZI® (durvalumab) in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival (EFS) and the key secondary endpoint of overall survival (OS) versus neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer (MIBC). Patients were treated with IMFINZIin combination with neoadjuvant chemotherapy before cystectomy (surgery to remove the bladder) followed by IMFINZI as adjuvant monotherapy. Approximately one in four patients with bladder cancer has evidence of the tumor invading the muscle wall of the bladder (without distant metastases), known as MIBC.

In the MIBC setting, approximately 117,000 patients are treated with current standard of care. Standard treatment includes neoadjuvant chemotherapy and radical cystectomy. However, even after cystectomy, patients experience high rates of recurrence and a poor prognosis.

IMFINZI was generally well-tolerated and no new safety concerns were observed in either the neoadjuvant or adjuvant setting. The safety profile ofIMFINZI and neoadjuvant chemotherapy was consistent with the known profile of the individual medicines. The addition of IMFINZI did not increase the discontinuation rate due to adverse events and did not compromise patients' ability to complete surgery compared to neoadjuvant chemotherapy alone.

These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. Immune-Mediated Pneumonitis: IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation.

IMFINZI as a Single Agent: In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions.

The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC or BTC when given in combination with chemotherapy. IMFINZI with IMJUDO: Immune-mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions. IMFINZI with IMJUDO and Platinum-Based Chemotherapy: Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.5%), and Grade 3 (1%) adverse reactions.

Immune-Mediated Colitis: IMFINZI with IMJUDO and platinum-based chemotherapy can cause immune-mediated colitis, which may be fatal. IMFINZI and IMJUDO can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis.

In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. IMFINZI as a Single Agent: Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions. IMFINZI with IMJUDO: Immune-mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%) adverse reactions.

Intestinal perforation has been observed in other studies of IMFINZI and IMJUDO. IMFINZI with IMJUDO and Platinum-Based Chemotherapy: Immune-mediated colitis occurred in 6.5% (39/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including fatal (0.2%) and Grade 3 (2.5%) adverse reactions. Intestinal perforation and large intestine perforation were reported in 0.1% of patients.

Immune-Mediated Hepatitis: IMFINZI and IMJUDO can cause immune-mediated hepatitis, which may be fatal. IMFINZI as a Single Agent: Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions. IMFINZI with IMJUDO: Immune-mediated hepatitis occurred in 7.5% (29/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4 (0.3%) and Grade 3 (4.1%) adverse reactions.

IMFINZI with IMJUDO and Platinum-Based Chemotherapy: Immune-mediated hepatitis occurred in 3.9% (23/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.3%), Grade 4 (0.5%), and Grade 3 (2%) adverse reactions.