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Dostarlimab is an anti-programmed cell death protein-1 antibody being evaluated in recurrent/advanced solid tumors, including non-small cell lung cancer (NSCLC), in the ongoing Phase I, multi-center, open-label, 2-part (dose escalation and cohort expansion) GARNET study (NCT02715284).Here, we report an interim analysis of patients with recurrent/advanced NSCLC who progressed following platinum-based chemotherapy. Patients received dostarlimab (500 mg IV every 3 weeks [Q3W] for Cycles 1-4, then 1000 mg Q6W) until disease progression or unacceptable toxicity for2 years. The primary endpoints were immune-related objective response rate (irORR) per investigator-assessed irRECIST and safety.As of 8, July 2019, 67 patients with recurrent/advanced NSCLC were enrolled and treated with dostarlimab; the majority had programmed death ligand 1 (PD-L1) tumor proportion score (TPS)1% (35.8% of patients) or PD-L1 TPS 1%-49% (29.9% of patients); 7.5% had PD-L1 TPS ≥ 50%, and 26.9% had unknown PD-L1 TPS status. Median follow-up was 13.8 months (range: 0.0-22.6). irORR was 26.9%, including 2 complete and 16 partial responses. The median duration of response of 11.6 months (range: 2.8-19.4). Responses were observed in 2 of 24 (16.7%) patients with PD-L1 TPS1%, 4 of 20 (20.0%) patients with PD-L1 TPS 1%-49% and 2 of 5 (40.0%) patients with PD-L1 TPS ≥ 50%. Fatigue (4.5%) was the most common Grade ≥ 3 treatment-related treatment-emergent adverse event (TRAE). Immune-related TRAEs (any grade) were observed in 28.4% of patients.Dostarlimab demonstrated promising antitumor activity in advanced/recurrent NSCLC that progressed following platinum-based chemotherapy, including across all PD-L1 subgroups, and has an acceptable safety profile.

5509 Background: Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the U.S. as a monotherapy in patients (pts) with dMMR AR EC that has progressed on or after treatment with a platinum-containing regimen or dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options; and in the E.U. as a monotherapy in pts with dMMR/MSI-H AR EC that has progressed on or after treatment with a platinum-containing regimen. Here, we report on efficacy and safety in the 2 expansion cohorts of the GARNET trial that enrolled pts with EC. Methods: GARNET is a multicenter, open-label, single-arm phase 1 study. Pts were assigned to cohort A1 (dMMR/MSI-H EC) or cohort A2 (MMRp/MSS EC) based on local assessment. Pts received 500 mg of dostarlimab IV Q3W for 4 cycles, then 1,000 mg Q6W until disease progression, discontinuation, or withdrawal. The primary endpoints are ORR and DOR by blinded independent central review using RECIST v1.1. Results: For this third interim analysis, 153 dMMR/MSI-H and 161 MMRp/MSS pts were enrolled and dosed. Of these, 143 dMMR/MSI-H and 156 MMRp/MSS pts had measurable disease at baseline and ≥ 6 mo of follow-up and were included in the efficacy-evaluable population. ORRs were 45.5% (dMMR/MSI-H) and 15.4% (MMRp/MSS; Table). Median (m) DORs were not reached (NR; dMMR/MSI-H) and 19.4 mo (MMRp/MSS). Probability of PFS at 6, 9, and 12 mo was 49.5%, 48.0%, and 46.4% in dMMR/MSI-H EC and 35.8%, 31.3%, and 29.4% in MMRp/MSS EC, respectively. mOS was NR (dMMR/MSI-H) and 16.9 mo (MMRp/MSS). Overall, 27 pts (8.6%) discontinued treatment because of a treatment-related adverse event (TRAE; 13 dMMR/MSI-H, 14 MMRp/MSS). The majority of TRAEs were grade 1 or 2. The most common any-grade TRAEs were fatigue (56; 17.8%), diarrhea (46; 14.6%), and nausea (43; 13.7%). No deaths were attributed to dostarlimab in the EC cohorts. Hypothyroidism (12; 8%) was the most common any-grade immune-related TRAE. Conclusions: Dostarlimab demonstrated durable antitumor activity in both dMMR/MSI-H and MMRp/MSS AR EC. dMMR/MSI-H was associated with better outcomes: a higher response rate and longer PFS and OS. Safety was consistent with other PD-1 antibodies. Clinical trial information: NCT02715284. [Table: see text]

2587 Background: Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the US as a monotherapy in pts with dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options; or dMMR advanced/recurrent (AR) endometrial cancer (EC) that has progressed on or after treatment with a platinum-based chemo; and in the EU as a monotherapy in pts with dMMR/ microsatellite instability–high (MSI-H) AR EC that has progressed on or after treatment with a platinum-based chemo. Here we report on efficacy and safety in 2 expansion cohorts that enrolled pts with dMMR solid tumors. Methods: GARNET is a multicenter, open-label, single-arm phase 1 study. Cohort A1 enrolled pts with dMMR/MSI-H AR EC; cohort F enrolled pts with dMMR/MSI-H/POLε-mut non-EC solid tumors. Pts received 500 mg of IV dostarlimab Q3W for 4 cycles, then 1000 mg Q6W until PD, discontinuation, or withdrawal. Primary endpoints were ORR and DOR by BICR per RECIST v1.1. Biomarker status was based on local assessment. Results: For this third interim analysis, 153 pts with dMMR/MSI-H EC and 210 pts with dMMR/MSI-H/POLε-mut non-EC solid tumors (56% colorectal cancer, 11% gastric) were enrolled and treated. Efficacy analysis was performed for 143 dMMR/MSI-H EC and 204 dMMR/MSI-H/POLε-mut non-EC pts who had measurable disease at baseline and ≥6 mo of follow-up. ORRs were 45.5% (dMMR/MSI-H EC) and 43.1% (dMMR/POLε-mut non-EC solid tumors; Table). Probability of PFS at 6, 9, and 12 mo was 49.5%, 48.0%, and 46.4% in dMMR/MSI-H EC and 51.8%, 48.1%, and 46.4% in dMMR/MSI-H/POLε-mut non-EC. Median (m) DOR and mOS were not reached for either cohort. A total of 13 pts (8.5%) with dMMR/MSI-H EC and 12 pts (5.7%) with dMMR/MSI-H/POLε-mut non-EC solid tumors discontinued owing to a treatment-related adverse event (TRAE). TRAEs occurring in ≥12% of pts were diarrhea, asthenia, fatigue, nausea, and pruritis (dMMR/MSI-H EC) and diarrhea, asthenia, and pruritus (dMMR/MSI-H/POLε-mut non-EC solid tumors). 2 deaths (1 hepatic ischemia, 1 suicide) were attributed by investigators to dostarlimab in pts with non-EC solid tumors. Conclusions: Dostarlimab demonstrated durable antitumor activity across 16 tumor types in pts with dMMR solid tumors, confirming efficacy in a larger sample size with extended follow-up. The safety profile was acceptable, with manageable toxicities. Clinical trial information: NCT02715284. [Table: see text]

201 Background: Dostarlimab is a programmed death receptor-1 (PD-1) blocking antibody that is approved in the US as a monotherapy in adult patients (pts) with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen or dMMR recurrent or advanced solid tumors that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. Here, we report on the antitumor activity and safety of dostarlimab monotherapy in pts with dMMR colorectal cancer (CRC), a post-hoc subgroup analysis of cohort F of the GARNET trial. Methods: GARNET is a phase 1, multicenter, open-label, single-arm study of dostarlimab monotherapy in pts with advanced or recurrent solid tumors. Cohort F of the GARNET expansion cohorts enrolled pts with dMMR/MSI-H or POLε mutated non-endometrial solid tumors, including pts with CRC. Pts must have progressed per blinded independent central review (BICR) following prior systemic therapy for advanced disease. Pts with CRC were required to have progressive disease after or been intolerant to fluoropyrimidine, oxaliplatin, and irinotecan. Pts received 500 mg intravenous dostarlimab every 3 weeks for 4 cycles, followed by 1000 mg every 6 weeks until discontinuation. Primary endpoints were objective response rate (ORR) and duration of response by BICR per RECIST v1.1. Pts were included in the efficacy analysis if they received ≥1 dose of dostarlimab, had measurable disease at baseline, and had ≥24 weeks of follow-up. All pts who received ≥1 dose of dostarlimab were included in the safety analysis. Results: As of the March 01, 2020 interim analysis data cut, 141 pts with dMMR non-endometrial solid tumors were included in the safety analysis, with 106 in the efficacy analysis. Of the pts in the efficacy analysis, 69 (65.1%) had CRC. Confirmed ORR by BICR per RECIST v1.1 in pts with dMMR CRC was 36.2% (95% CI, 25.0%–48.7%). There were 3 complete responses and 22 partial responses. At the data cut, 23 pts (92%) were still on treatment. Median duration of response had not been reached for pts with CRC. In the overall dMMR non-endometrial solid tumor population, treatment-related adverse events (TRAEs) were reported in 68.1% of pts, with 8.5% of pts experiencing at least 1 grade ≥3 TRAE. The most common grade ≥3 TRAE was lipase increased in 2 (1.4%) of pts. Only 5 pts (3.5%) discontinued dostarlimab due to at TRAE. Treatment-related serious AEs were reported in 9 (6.4%) pts. Conclusions: Dostarlimab demonstrated durable clinically meaningful antitumor activity in pts with dMMR CRC, which was consistent with that seen in patients with dMMR non-CRC solid tumors. No new safety signals were detected in patients with dMMR non-endometrial solid tumors. Clinical trial information: NCT02715284.

Objectives: Patients with head and neck squamous cell carcinoma (HNSCC) can experience severe symptom burden and/or difficulty swallowing, leading to problems with treatment adherence/administration. In LUXHead and Neck 1 (LH & N1; NCT01345682), second-line afatinib improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic HNSCC. We report adherence and safety across pre-specified and additional subgroups potentially linked to afatinib PFS benefit in LH&N1 (p16 status, smoking history), and afatinib adherence, safety and efficacy by administration (oral versus feeding tube; post-hoc analysis). Methods: Patients were randomized (2:1) to afatinib (40 mg/day) or intravenous methotrexate (40 mg/m(2)/ week). Results: Among 320 afatinib-treated and 160 methotrexate-treated patients, 83-92% and 76-92% (of patients with data available) across all subgroups took >= 80% of treatment. Across p16 status and smoking history subgroups, the most common treatment-related adverse events (AEs) were diarrhea (70-91%), rash/acne (72-84%), stomatitis (34-73%) with afatinib; and included stomatitis (39-100%), fatigue (22-50%), nausea (19-36%) with methotrexate. Dose reduction decreased AE incidence/severity. Baseline characteristics were generally similar between oral/feeding tube (n = 276/n = 46) groups. 89%/89% (of patients with data available) took >= 80% of assigned afatinib. Median PFS was 2.6 versus 2.7 months (hazard ratio: 0.997; 95% confidence interval: 0.72-1.38). The most common afatinib-related AEs were: rash/acne (74% versus 74%), diarrhea (73% versus 65%), stomatitis (40% versus 30%). Conclusion: Subgroup analyses of LH&N1 demonstrate that afatinib has predictable and manageable safety across patient subgroups, with high treatment adherence, and is effective via oral and feeding tube administration.

Autoimmune hemolytic anemia and thrombocytopenia (AIHA/AITP) frequently complicate the course of non-Hodgkin lymphomas, especially low-grade, but they are very rarely observed in Hodgkin lymphoma (HL). Consequently the frequency and the profile of patients with HL-associated AIHA/AITP have not been well defined. Among 1029 patients with HL diagnosed between 1990 and 2010, two cases of AIHA (0.19%) and three of AITP (0.29%) were identified at the presentation of disease. These patients were significantly older, and more frequently had features of advanced disease and non-nodular sclerosing histology, compared to the majority of patients, who did not have autoimmune cytopenias at diagnosis. ABVD combination chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) provided effective control of HL and the autoimmune condition as well. During approximately 6600 person-years of follow-up for the remaining 1024 patients, seven (0.7%) patients developed autoimmune cytopenias (three AITP, three AIHA, one autoimmune pancytopenia) for a 10- and 15-year actuarial incidence of 0.95% and 1.40%, respectively. Their features did not differ compared to the general population of adult HL. In this large series of consecutive, unselected patients, those who presented with autoimmune cytopenias had a particular demographic and disease-related profile. In contrast, patients developing autoimmune cytopenias during follow-up did not appear to differ significantly from those who did not.