First Clinical Trials Plenary features practice-changing data from phase III trials

Matthew J. Matasar, MD
Matthew J. Matasar, MD

Results of a randomized phase III trial suggest a new treatment option for patients with relapsed indolent non-Hodgkin Lymphoma (iNHL). Copanlisib plus rituximab improved overall survival compared to rituximab alone.

“Copanlisib is the first PI3K inhibitor to be safely combined with rituximab and the first to demonstrate broad superior efficacy in combination with rituximab in all indolent NHL histologies,” said Matthew J. Matasar, MD, Sloan Kettering Cancer Center Bergen. “Copanlisib plus rituximab represents a new treatment option for patients with relapsed disease across all subtypes of indolent NHL.”

Matasar presented the results from the CHRONOS-3 trial during Phase III Clinical Trials: Dedicated to the Memory of José Baselga on Saturday, April 10. Registrants can watch a replay of this clinical trial plenary anytime until June 21, 2021.

Results were published simultaneously in The Lancet Oncology. The trial included 203 participants who received copanlisib plus rituximab and 149 who received rituximab plus placebo. After a median of 19.2 months of follow-up, median progression free survival for those on combination treatment was 21.5 months vs. 13.8 months for rituximab alone, (HR 0.52, p <0.0001), Matasar reported. Results were similar across all patient subgroups and iNHL histologies. The safety profile for the combination therapy was similar to the agents as monotherapy.


Tebentafusp as first-line treatment for metastatic uveal melanoma

Jessica Hassel, MD
Jessica Hassel, MD

The first phase III data on tebentafusp versus investigator’s choice of treatment, which includes immune checkpoint inhibitors, as a first-line treatment in metastatic uveal melanoma are in. A trial of tebentafusp versus pembrolizumab, ipilimumab, or dacarbazine in 378 patients showed a clear benefit for tebentafusp. Median survival on tebentafusp was 21.7 months versus 16 months on investigator’s choice of treatment (HR 0.51, p <0.0001).

“There is a clear and early separation of benefit for patients receiving tebentafusp,” said Jessica Hassel, MD, University Hospital Heidelberg. “Tebentafusp has the potential to be practice-changing in the treatment of uveal melanoma.”

Hassell presented the results of IMCgp100-122, the first trial to improve overall survival in metastatic uveal melanoma. She noted that tebentafusp is the first T-cell receptor therapy to demonstrate overall survival benefit. Adverse events were generally manageable, and related discontinuation rates were low, 2 percent for tebentafusp versus 4.5 percent for immunotherapy.


Nivolumab + chemotherapy superior to chemotherapy alone as neoadjuvant treatment for resectable NSCLC

Patrick M. Forde, MBBCh
Patrick M. Forde, MBBCh

Neoadjuvant or adjuvant chemotherapy is recommended for patients with resesctable non-small cell lung cancer (NSCLC) at high risk of recurrence. Early data from the open label CheckMate 816 trial suggest that combining nivolumab (NIVO) and chemotherapy is superior to chemotherapy alone in the neoadjuvant setting.

Combination neoadjuvant treatment had an odds ratio of 13.94 for pathological complete response (pCR), with 24 percent pCR rate for combination treatment versus 2.2 percent for chemotherapy alone (p <0.0001). In this trial, pCR was defined as no residual viable tumor cells in the primary tumor or in sampled lymph nodes.

“CheckMate 816 is the first phase III study to show the benefit of neoadjuvant immunotherapy + chemotherapy for resectable NSCLC,” said Patrick M. Forde, MBBCh, Thoracic Cancer Clinical Research Program and Johns Hopkins Kimmel Cancer Center. “NIVO, in combination with chemotherapy, could represent a potential new neoadjuvant option for these patients.”

The study randomized 358 newly diagnosed NSCLC patients eligible for surgery to neoadjuvant therapy using NIVO + chemotherapy or chemotherapy alone. The median age was about 65. Roughly half the patients are in Asia, with the balance in Europe or North America.

Patients were followed for a median of 7.6 months for a preplanned analysis of pCR. The trial is ongoing to assess event-free survival and overall survival, Forde said.

Safety profiles were similar across both arms of the trial. The most frequent adverse events were nausea, anemia, constipation, decreased appetite, neutropenia, and decreased neutrophil count.


Adding ipilimumab to adjuvant nivolumab does not improve resected melanoma outcome

Georgina V. Long, PhD, MBBS
Georgina V. Long, PhD, MBBS

The combination of ipilimumab (IPI) plus nivolumab (NIVO) as adjuvant therapy was not superior to NIVO alone in patients with resected stage III-B-D/IV melanoma in the Checkmate 915 trial. The trial compared the two regimens in 1,844 patients from 122 sites across 19 countries.

recurrence-free survival was similar in both groups, 64.6 percent for NIVO + IPI and 63.2 percent for NIVO alone. Recurrence-free survival was also similar in a subgroup of patients with PD-L1 ˂1 percent, 53.6 percent, and 52.4 percent, respectively, for those in the NIVO + IPI arm and NIVO alone arm. Earlier trials had suggested a potential benefit for patients with low PD-L1 levels.

“We saw no benefit in any subgroups in the trial,” said Georgina V. Long, PhD, MBBS, Melanoma Institute Australia and Royal North Short Hospital, The University of Sydney. “These results reaffirm NIVO as the adjuvant standard of care in this population.”

There were no surprises in the safety profiles, Long said. Adverse events were as expected in both groups and there were no clinically significant differences in quality of life.