DURVALUMAB TREATMENT FOUND SAFE IN PATIENTS WITH HIV
Abstract 2501: Phase II study of durvalumab (MEDI4736) in cancer patients HIV-1-infected
Solid-tumor patients with HIV were treated with durvalumab in a study presented by Dr. María González-Cao (Instituto Oncológico Dr. Rosell, Barcelona, Spain). Patients with HIV have traditionally been excluded from immunotherapy clinical trials; thus, this presentation assessed an under-evaluated population. Patients were treated with durvalumab 1500 mg Q4W to determine the safety and feasibility of ICB in this subpopulation, as well as to determine response rates, and evaluate the impact of viral infection on immunotherapy treatment response or resistance.
Twenty patients were enrolled, all of whom maintained their antiretroviral therapy throughout the course of immune checkpoint blockade. Global AEs were presented, with 75% of patients experiencing a grade 1 AE, 50% grade 2, 5% grade 3-4, and 2 instances of grade 5 AEs, which the investigators do not believe were related to the study drug. Overall, the best responses achieved included partial response in 20% of patients, stable disease in 25%, and disease progression in 55%. In those patients achieving a response, the median duration was 6.5 months. At cut-off, eight patients were still on-treatment. A trend toward higher responses was noted in PD-L1+ patients, although the sample size was small. Notably, no viral reactivation was observed during PD-L1 blockade. This study indicated a favorable toxicity profile of durvalumab in solid tumor patients with HIV, with encouraging efficacy.
CONFIRMATION OF PEMBROLIZUMAB AS 2ND-LINE THERAPY FOR ADVANCED HCC
Abstract 4004: Results of KEYNOTE-240: phase 3 study of pembrolizumab (Pembro) vs best supportive care (BSC) for second line therapy in advanced hepatocellular carcinoma (HCC)
Dr. Richard S. Finn (University of California – Los Angeles, Los Angeles, CA) presented the results of a phase III study of pembrolizumab + best supportive care (BSC) compared to placebo + BSC in 2nd-line treatment of HCC. Pembrolizumab was administered at 200 mg Q3W, and the primary endpoints of this randomized study were OS and PFS.
Pembrolizumab treatment improved OS and PFS relative to placebo (HR [one-sided p]: 0.78 [0.0238] and 0.78 [0.0186] respectively), but these increases did not meet the pre-specified statistical criteria. An improvement in ORR was also noted with pembrolizumab treatment, at 18.3% vs 4.4%, with 6 CRs noted in the pembro-treated population. The safety profile of pembrolizumab was similar to that reported in previous HCC studies. The authors hypothesized that the OS results were likely impacted by subsequent anti-cancer therapy in the placebo arm, as many of these off-study patients received new therapy. However, even though the pre-specified boundaries were not reached, these results reinforce those found in the previous KEYNOTE-224 study and lend support to pembrolizumab in 2nd-line treatment of HCC.
MODEST GAINS WITH PEMBROLIZUMAB IN G/GEJ ADENOCARCINOMA
Abstract LBA4007: Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study
In this late-breaking presentation, Dr. Josep Tabernero (Vall d'Hebron University Hospital and Institute of Oncology) presented the results of the phase III KEYNOTE-062 study in gastric and gastroesophageal junction adenocarcinoma. Patients were randomized to either pembrolizumab (P, 200 mg Q3W), P + chemotherapy (P+C, cisplatin 80 mg/m2 + 5-FU 800 mg/m2/d on d1-d5 Q3W, or capeitabine 1000 mg/m2 BID on d1-d14 Q3W per local guidelines), or chemotherapy + placebo Q3W (C). The primary endpoints were OS in the CPS >=1 and >=10 groups receiving P+C vs C and P vs C, and PFS in the same PD-L1 subgroups in P+C vs C. Secondary endpoints included ORR in the CPS >=1 subgroup for P+C vs C.
With a median follow-up of 11.3 months, no significant difference was found when comparing patients treated with P vs C in terms of overall survival in the CPS >=1 group (mOS with P: 10.6 mo; with C: 11.1 mo), while a clinically-meaningful improvement in OS was noted in those patients with CPS >=10 (mOS with P: 17.4 mo; with C: 10.8 mo). Additionally, those responses that were observed with P treatment lasted much longer than those obtained with C. In CPS >=1 patients treated with P+C compared to C alone, once again no statistical difference was found in the OS: 12.5 mo with P and 11.1 mo with C. Modest gains were noted in PFS and ORR for patients with highly-PD-L1-expressing tumors when treated with P+C as well. In all cases, the AE profiles were as expected. This study indicated that pembrolizumab had similar benefit to chemotherapy in first-line treatment of gastric/GEJ cancers in overall population with lower adverse events, any grade (54% vs 92%) and grade 3-4 (16% vs 68%). Pembrolizumab + chemotherapy displayed only a small additional benefit versus chemotherapy with manageable safety profile.
ANTI-BCMA BITE SHOWS PROMISE IN FIRST-IN-HUMAN R/R MULTIPLE MYELOMA STUDY
Abstract 8007: Evaluation of AMG 420, an anti-BCMA bispecific T-cell engager (BiTE) immunotherapy, in R/R multiple myeloma (MM) patients: Updated results of a first-in-human (FIH) phase I dose escalation study
The safety and activity of AMG 420/BI 836909, a BCMA/CD3 bispecific, were evaluated in a first-in-human study presented by Dr. Max S. Topp (University Hospital Würzburg, Würzburg, Germany). R/R multiple myeloma patients were administered AMG 420 at 0.2-800 µg/d for a mean of 2.7 cycles.
Serious AEs occurred in 45% of patients, with infections and polyneuropathy being the most common, while grade 2-3 CRS was noted in 3 patients. The highest administered dose (800 µg/d) resulted in 2/3 patients with DLTs, indicating this dose was not tolerable. At 400 µg/d, 5/10 patients demonstrated minimal residual disease-negative sCRs, 1 patient had a VGPR, and 1 had a PR, adding up to a 70% response rate. These responses were durable, lasting a median of 9.0 months at data cut-off. Pooling all dose groups, the response rate was 31%. As a result of this study, 400 µg/d was recommended for further study in R/R MM patients.