High-dose ipilimumab augments nivolumab benefit for TCC

In the phase II TITAN-TCC* trial presented at ASCO GU 2022, the addition of ipilimumab to nivolumab led to improved responses in patients with pretreated (second/third line) advanced/metastatic or surgically unresectable transitional cell carcinoma (TCC).

In this study, 83 patients (median age 68 years, 69 percent male) received induction treatment with IV nivolumab 240 mg Q2W for 8 weeks. The maintenance phase ensued thereafter, wherein nonresponders (ie, those who had stable/progressive disease [SD/PD]; n=50) received at least one “boost” cycle comprising IV nivolumab 1 mg/kg and ipilimumab 3 mg/kg Q3W. Of these, 44 received two cycles after week 8, while the rest who continued to have SD/PD after the initial boost doses received two more cycles. Those who achieved complete/partial response (CR/PR) after induction continued with their induction regimen during the maintenance phase. [ASCO GU 2022, abstract 441]

A majority of participants (87 percent) had TCC in the bladder, and gemcitabine-cisplatin was the most commonly used first-line systemic therapy regimen (84 percent). Thirty-four percent had PD-L1 expression ≥1 percent.

After a median follow-up of 5.6 months, a third of participants achieved best objective response (BOR) following receipt of the nivolumab-ipilimumab boost (p<0.01), an improvement from the 20-percent BOR observed at week 8 following nivolumab monotherapy.

When results were stratified according to PD-L1 status, the boosts led to improvements in objective response rates (ORRs) observed at week 8, rising from 32 percent to 46 percent among patients with PD-L1 expression, and doubling (from 12 percent to 24 percent) among those who were PD-L1-negative.

Following the first boost cycle, 13 achieved SD, four of whom achieving CR (n=1) and PR (n=3). Of those who had PD (n=31), four had PR while two had SD.

Among participants who received additional boosts, two went on to have PR while one had SD.

“Boost” boosts responses

Taken together, these findings suggest that boosting improved the best response, said Professor Marc-Oliver Grimm from Jena University Hospital, Jena, Germany, in his presentation. “[Our findings show that] after prior platinum-based chemotherapy [in patients with advanced TCC], treatment with nivolumab and nivolumab-ipilimumab boosts in nonresponders significantly improved ORR compared [with] nivolumab second-line monotherapy. Patients with PD-L1 positive tumours appeared to benefit the most.”

The results thus reinforce studies reflecting improved outcomes for dual checkpoint inhibition with nivolumab and ipilimumab in metastatic urothelial carcinoma (UC), particularly with higher ipilimumab doses (ie, 3 mg/kg), Grimm added. “Our study provides further evidence for the added value of high-dose ipilimumab in metastatic UC.”

Follow up is underway to validate the long-term survival outcomes with this tailored immunotherapy approach, noted Grimm. At the time of this analysis, median progression-free survival was 1.9 months, while median overall survival was 7.6 months.