Pembrolizumab is used routinely in advanced NSCLC. Combination strategies, such as with RT are of great interest. We report on safety and tolerability of an open-label phase 1 trial for cohort 1 of pembrolizumab with 2 schedules of palliative RT.
All cohort 1 patients started with a pembrolizumab dose of 100mg given 2 weeks prior to RT, and then received pembrolizumab 100mg 2-weekly concurrently with RT, followed by maintenance dose 200mg pembrolizumab 3-weekly. The RT was either 20 Gy/5# (low dose RT - LD) or 36 Gy/12# (high dose RT - HD). Cohort 2 pembrolizumab dose will be 200mg, for all doses, with the same RT schedules. Dose limiting toxicity (DLT) period, 2 months from completing RT, is defined as grade (G) 2 pneumonitis, G4 oesophagitis or G2 myelitis.
3/6 pts in the LD and 6/8 pts in the HD were evaluable for DLTs. Mean age was 61 years, 64% were female, 71% were smokers, ECOG performance status was 1 in 100%. 57% were of non-squamous histology with no driver mutations, and 64% were PD-L1 positive (TPS ≥1%). All pts had adverse events (AEs); G3–4 AEs were seen in 66.7% in the LD and 37.5% in the HD. There were no DLTs. In the LD, G3 AEs included: anaemia (n = 1), back pain (n = 1), bronchitis (n = 1), dyspnoea (n = 1), fatigue (n = 1), hypokalaemia (n = 1), hypophosphataemia (n = 1), and syncope (n = 2). In the HD, 1 pt had drug induced liver injury (G1 ALT, G3 ALP, G2 AST, G1 bilirubin, G4 GGT), and so the cohort was expanded by a further 3 pts. No DLTs were seen. G3 AEs included: pneumonia (n = 1), back pain (n = 1), dehydration (n = 1), radiation dermatitis (n = 1), diarrhoea (n = 1), hyperglycaemia (n = 1), and hypokalaemia (n = 2). 1 pt had G4 urosepsis. In the LD and HD, pts also had RT dermatitis (G1 n = 11, G2 n = 2), RT esophagitis (G1 n = 10, G2 n = 4), and RT pneumonitis (G1 n = 6). With a median follow-up of 7.9 months, median PFS was 1.3 months in the LD and 3.7 months in the HD (HR 0.28, P = 0.056). Median OS was 5.2 months in the LD and 8.3 months in the HD (HR 0.59, P = 0.441). Disease control rate (DCR) was 37.5% in the LD (3 SD) and 62.5% in the HD (3 PR, 2 SD; P = 0.592). DCR did not correlate with PD-L1 status (P = 1.00).
Combining pembrolizumab and palliative thoracic RT appears to be safe and tolerable with both RT doses. This trial continues to recruit to cohort 2.
Clinical trial identification
Legal entity responsible for the study
Royal Marsden Clinical Trials Unit, Royal Marsden NHS Foundation Trust, Downs Road, Sutton, United Kingdom.
Merck Sharp Dohme.
There was no editorial assistance sort.
R. Kumar, A. Tree, S. Lalondrelle: Research grants: MSD. D.P. Walder: Research grants: BMS. J. Bhosle: Honoraria: BMS; Travel grants: BMS. S. Popat: Honoraria: MSD and BMS. F. McDonald, K. Harrington, R. Huddart: Research grants and Honoraria: MSD. M.E.R. O’Brien: Research grants: MSD; Honoraria: MSD and BMS. M. Ahmed: Research grants: MSD and BMS. All other authors have declared no conflicts of interest.