Investigators Release Results of 4 Trials of Immunotherapy Drugs

Investigators released results from 4 different trials of immunotherapy drug combinations at the American Association for Cancer Research Annual Meeting 2022 in New Orleans, Louisiana.

In the first trial, presented by Ari VanderWalde, MD, MPH, from the West Cancer Center, SWOG1616, investigators tested strategies that combined ipilimumab (Yervoy, Bristol Myers Squibb), an anti-CTLA-4 agent, and nivolumab (Opdivo, Bristol Myers Squibb), an anti- programmed cell death protein 1 (PD)-1 agent compared with just ipilimumab alone.

The trial included 91 individuals with advanced melanoma refractory to anti-PD-1 or programmed death-ligand 1 (PD-L1). Individuals were randomized 1 to 3 to either the monotherapy or the combination therapy. Additionally, they also had periodic biopsies, blood samples, and imaging and remained on treatment until progression. The follow up continued until death or 2 years after the treatment was stopped.

The combination therapy showed improvement in progression-free survival (PFS) with an objective response rate (ORR) of 28% combined with 9% in the monotherapy arm. Investigators also found that a 6-month PFS was approximately 34% in the combination arm compared with 13% in the monotherapy arm.

Additionally, the combination therapy increased CD8+ cells in the tumor and boundary, particularly among responders.

Approximately 87% of individuals in the monotherapy arm and 93% in the combination therapy arm reported treatment-emergent adverse events (AEs), with the most common being diarrhea. The combination arm had more grade 3 to 5 toxicities, and all toxicities were consistent with prior reports.

In the second trial, investigators found that BO-112, a nanoplexed double-stranded RNA that activates TLR3, RIG-1, and MDA5, can reverse anti-PD-1 resistance when directly injected into tumors.

In combination with pembrolizumab (Keytruda, Merck), BO112 had a disease control rate of 68% and an ORR of 30% in individuals with advanced melanoma resistant to anti-PD-1 alone.

The median duration of response has not been reached. The median PFS was 3.8 months but has not been reached with individuals with non-acral disease.

The SPOTLIGHT-203 trial had 42 individuals with unresectable cutaneous, acral, or mucosal melanoma resistant to anti-PD-1 therapy with injectable disease. They received intratumoral BO-112 injections up to 2 mg in up to 8 lesions per cycle with intravenous pembrolizumab every 3 weeks.

In a third study presented by Zev A. Wainberg, MD, from the University of California in Los Angeles, investigators combined TTX-030, a novel CD39 antibody, with budigalimab (AbbVie) and Folfox chemotherapy in 44 individuals with gastric or gastroesophageal junction.

They found that the combination showed promising results with an ORR of approximately 52.5% and a disease control rate of 92.5% as a first-line treatment. More than half the individuals were still in the study after 60 weeks.

Most individuals reported AEs, and 61.4% had a grade 3 or 4, with most related to the chemotherapy component.

In the fourth trial, investigators combined CTLA-4 blockade, MEDI5752, with PD-1 inhibition and found that it is an effective antitumor strategy that improved survival at higher rates than anti-CTLA doses, but higher doses caused more serious AEs.

Investigators included 61 individuals in a dose-escalation arm and 25 individuals in a dose-expansion arm. They found that there were durable responses in individuals with a variety of advanced solid tumors who were naïve to immunotherapy across doses.

The ORR was 19.8%, with a disease control rate of 53.3% and a median duration of response of 17.5 months.

Approximately 85% of individuals reported AEs, with 38.4% reporting grade 3 or 4, mostly in the 1500-mg and higher groups. Two individuals discontinued the drug because of AEs, with 1 taking 2000 mg and 1 taking 2500 mg.

Reference

Researchers report results from four trials of immunotherapy drug combinations. AACR Meeting News. News release. April 13, 2022. Accessed April 13, 2022. https://www.aacrmeetingnews.org/news/researchers-report-results-from-four-trials-of-immunotherapy-drug-combinations/