Dose Of Pembrolizumab Research Articles

Cost and efficacy of low-dose pembrolizumab in the treatment of non-small cell lung cancer patients in Asia.

e19385 Background: Pembrolizumab has dramatically improved the survival of patients with non-small cell lung cancer (NSCLC) and is considered the standard of care for first line treatment of NSCLC who do not harbour oncogenic drivers. The fixed dose of 200mg was approved by the US Food and Drug Administration. The dose of 200mg was based on pharmacokinetic analysis. Studies have demonstrated equivalent efficacy with weight-based dosing 2mg/kg. An average Asian weighs 50-60kg. We aimed to look at the efficacy of pembrolizumab at a low fixed dose compared to the standard dosing. Methods: A review of all consecutive patients receiving pembrolizumab for advanced NSCLC from January 2016 to December 2019 in a large, high-volume academic medical centre, the National University Hospital, Singapore was conducted. Data fields collected include patient’s demographics, treatment doses and clinical characteristics. Time on treatment and overall survival were analysed using the Kaplan Meier method. Results: In total, 92 ECOG 0-2 patients with advanced NSCLC were treated with pembrolizumab. Median age was 69 years (Range, 29-92). Most were males (76%) and Chinese race (68%). Of the 92 patients, 46 (50%) and 46 (50%) received 100mg (Pem100) and 200mg (Pem200) of pembrolizumab respectively. Pembrolizumab was prescribed as first line in 73 (79%) and second line in 19 patients (21%). The average dose of pembrolizumab received in the low dose group was 1.87mg/kg (Range, 1.24mg/kg – 2.70mg/kg). 88 patients were included in the survival analysis. 4 were excluded due to the presence of an oncogenic driver. Patients were followed up for a median of 13.2 months. There was no difference in progression free survival between Pem100 and Pem200 for first-line single agent and when combined with chemotherapy (PFS: NR versus 5.3months, HR 2.17, 95% CI 0.76-6.16, p = 0.15 and NR vs 16.9 months, HR 2.89, 95% CI 0.35-25.16, p = 0.33 respectively). For patients who received pembrolizumab in the first line setting, the response rate was 56% vs 20% (p = 0.07), 67% vs 52% (p = 0.69) for Pem100 and Pem200 as a single agent and when combined with chemotherapy respectively. The median number of cycles received was 8.9 (Range, 1-60 cycles), translating to estimated cost savings of SGD 45 395 (~ USD 32 664) per patient who received Pem100. Conclusions: A lower fixed dose of pembrolizumab at 100mg showed no difference in progression free survival and response rate in an Asian cohort with significant cost savings. A further randomised controlled trial in an Asian population should be carried out.

Phase I Alexander study of AUTO3, the first CD19/22 dual targeting CAR T cell therapy, with pembrolizumab in patients with relapsed/refractory (r/r) DLBCL.

8001 Background: CD19 directed CAR T cells are effective in patients with r/r DLBCL, however relapses due to CD19 loss or PDL1 upregulation are common. In this study, we evaluate the safety and efficacy of AUTO3, a CAR T targeting CD19/22 with limited duration of PD-1 blockade. Methods: We constructed a bicistronic retroviral vector encoding both an anti-CD19 (OX40 co-stim) and an anti-CD22 (41BB co-stim) CAR with humanized binders. The cell product was manufactured in a semi-automated and closed process using CliniMACS Prodigy. Patients (≥ 18 years) with r/r DLBCL (NOS) or transformed (tDLBCL); ECOG <2, adequate organ function are eligible. Lymphodepletion was Flu/Cy prior to AUTO3. Bridging therapy was allowed. The three dose levels explored are 50, 150, and 450 x 10^6 CAR T cells. Patients received AUTO3 alone, or with 3 doses of pembrolizumab (pem) 200 mg q 3 wks starting on D14 (regimen A), or with a single dose of pem 200 mg on D-1 (regimen B). The primary endpoint is frequency of DLTs and grade (G) 3-5 adverse events (AE) and secondary endpoints included ORR, CRR, and biomarkers. Results: As of Jan 21, 2020, 28 patients underwent leukapheresis, 27 successfully manufactured, 1 being manufactured, and 19 patients treated with AUTO3. The median age was 57 (28 - 71) and median number of prior therapies was 3 (2 - 10). 89% had refractory disease, 74% were DLBCL NOS, and 26% were tDLBCL. Dose escalation from 50 to 450 x 106 cells with pem regimen A and B have been completed without DLTs. G > 3 treatment emergent AEs that occurred > 15% were neutropenia (89%), thrombocytopenia (58%), anemia (47%), febrile neutropenia (16%), and hypophosphataemia (16%). Across all dose levels, there were 0% sCRS with primary infusion and 5% severe neurotoxicity (sNT) (1/19), which resolved. There were no cases of sCRS and no neurotoxicity of any grade at > 50 x 106 cells. Eighteen patients were evaluable for efficacy. Among the 11 treated at dose > 50 x 106, the ORR and CRR were 64% and 55%, and all CRs are ongoing (1-12 mth). Two out of 3 patients achieved CR at 450 x 106 cells on pem regimen B. Additional patients and longer follow up, as well as biomarkers, will be presented. Conclusions: AUTO3 at > 50 x 106 CAR T cells with pembrolizumab induces CRs without severe CRS or neurotoxicities of any grade. Clinical trial information: NCT03287817 .

Initial safety run-in findings with bavituximab plus pembrolizumab in patients with advanced gastric or gastroesophageal cancer.

e16537 Background: Bavituximab, an investigational, chimeric monoclonal antibody designed to inhibit the immunosuppressive effects of phosphatidylserine (PS), is being evaluated in combination with pembrolizumab in patients with advanced gastric and gastroesophageal junction (GEJ) cancer. Bavituximab binds in a high-affinity complex with β2-glycoprotein and PS to reverse immunological non-responsiveness and activate multiple immune cell receptors. Post-hoc data from the Phase III Sunrise second-line lung cancer study indicated that patients who progressed on study treatment with bavituximab plus docetaxel and continued with a checkpoint inhibitor showed significantly improved overall survival. Cumulative data suggest that bavituximab may potentiate pembrolizumab-mediated checkpoint inhibition, potentially increasing overall clinical benefit. ONCG100 is a phase 2, multicenter, open-label, single-arm global study designed to assess the safety, tolerability and efficacy of bavituximab and pembrolizumab when administered in combination to advanced gastric or GEJ adenocarcinoma patients, regardless of PD-L1 status, who have progressed on or after at least one prior standard therapy (NCT04099641). Methods: The safety run-in phase of the trial evaluated the safety and tolerability of de-escalating doses of bavituximab when administered in combination with the approved dose and schedule of pembrolizumab (200mg, Q3W). Adverse events were evaluated by CTCAE v5.0. Results: Three patients enrolled and completed the safety-run in phase of the study where bavituximab was administered at the starting dose of 3 mg/kg QW in combination with pembrolizumab. There were no dose-limiting toxicities observed during the 21-day monitoring period. A total of 4 treatment emergent adverse events were observed; 2 of which were reported as related to treatment with bavituximab (arthralgia and fatigue, both grade 1). There was one treatment-unrelated SAE reported (chylous ascites, grade 2), which resolved allowing the patient to continue treatment. Conclusions: The 3 mg/kg dose of bavituximab was readily combined during the safety run-in phase of the study with the approved dose of pembrolizumab. The AE profiles for this combination were manageable and expected given the known profiles of each agent. Based upon these findings, the recommended dose for expansion for the combination was declared and the expansion phase of the study opened. Updated safety data from the study will be presented. Clinical trial information: NCT04099641 .

AST-008: A novel approach to TLR9 agonism with PD-1 blockade for anti-PD-1 refractory Merkel cell carcinoma (MCC) and cutaneous squamous cell carcinoma (CSCC).

TPS3164 Background: AST-008 is a potent spherical nucleic acid configuration of a toll-like receptor (TLR) 9 agonist oligonucleotide being developed for the treatment of MCC and CSCC in patients (pts) progressing on immune checkpoint inhibitor (CPI) monotherapy. Previously presented data suggests AST-008 elicits a Th1-type cytokine response and immune cell activation. This parallel-arm phase II design will permit assessment of efficacy in two advanced skin cancers with high unmet medical need. Methods: The study has an open label, multicenter phase Ib/II dose escalation/expansion design. The phase 1b dose escalation used a 3+3 design with increasing doses of intratumoral (IT) AST-008 plus standard flat dose pembrolizumab. The phase II dose expansion is using the recommended regimen (RP2D) of IT AST-008 plus flat dose pembrolizumab or cemiplimab to treat two cohorts of pts with advanced/metastatic MCC or CSCC, respectively. The key objective of the phase II expansion is to provide an estimate of preliminary efficacy of IT AST-008 with pembrolizumab or cemiplimab in pts whose disease progressed on a single-agent CPI therapy. Endpoints also include safety, pharmacokinetic and pharmacodynamic assessments. Pts must have at least two evaluable lesions by RECIST v1.1. One or more lesions may be injected with AST-008, but one lesion (the “witness” lesion) must remain un-injected throughout the study to differentially assess effects of AST-008 on the injected and witness lesions. The RP2D of AST-008 was derived from the dose escalation phase together with pembrolizumab. That RP2D is being used not only in the MCC cohort where AST-008 is combined with pembrolizumab, but also in the CSCC cohort where AST-008 is combined with cemiplimab. To ensure safety of the AST-008/cemiplimab combination, the first 6 pts in the CSCC cohort will be monitored for dose limiting toxicities through the first 5 weeks of dosing, and then the data review committee will assess safety before approving additional patient enrollment to that cohort. Each expansion cohort will enroll up to 29 pts with a Simon two-stage optimal design. In the first stage, 10 pts will be accrued. If there are 0 responses in these 10 pts, enrollment in that arm will be stopped. Otherwise, 19 additional pts will be accrued for a total of 29. The null hypothesis will be rejected if 4 or more responses are observed in 29 pts. This design yields a type I error rate of 0.05 and power of 80% when the true response rate is 20%. The planned phase II enrollment is 58 pts across about 15 US-based sites. Clinical trial information: NCT03684785 .

Retrospective analysis of clinical outcomes of patients with advanced non-small cell lung cancer (NSCLC) exposed to immunotherapy: The experience of the Oncology Center of Hospital Moinhos de Vento.

e21720 Background: Lung cancer has the highest mortality rate among malignant neoplasms worldwide. Most cases present an advanced stages. From the last few years, the target drugs and immunotherapy (IO) have emerged as important therapeutic options in this scenario. In Brazil, in 2018, this disease was responsible for 8.7% of cases of malignant neoplasms in men and 6.2% of cases in women. When looking at data from our state, Rio Grande do Sul, the highest rates in the country are noted, with an estimated rate of 40.22 cases for every 100 thousand men and 20.49 cases for every 100 thousand women. Although the available trials point to significant improvements in the clinical outcomes, the real impact of using such treatments on patients in our community practice, real-world scenario, is unknown. Methods: Through the detailed analysis of the institutional electronic medical record, we included patients with metastatic NSCLC, followed up on an outpatient basis at the Oncology Center of Hospital Moinhos de Vento, who had received at least one dose of nivolumab, pembrolizumab or atezolizumab, either as monotherapy or in combination therapy with chemotherapy, in any line of cancer treatment, in the period from January 2015 to June 2019. Primary endpoint was overall survival (OS) and secondary endpoints were time-to-treatment discontinuation (TTD) and treatment-related toxicity (TRT). Results: 41 patients met criteria. The sample consisted of patients with a mean age at diagnosis of 67.7 years, the majority being male (53.7%), stage IVB disease (53.7%), previously smokers (61%) and with non-squamous NSCLC (75.6%). Central nervous system (CNS) metastases were present in 26.8% of patients. About 51.3% (n = 21) received IO as second line or later treatment. At this group, nivolumab was the main IO (81%). The median OS in the first line (1L) of treatment was not reached while in second line and beyond was 10.0 months (3.4 - 16.5), with no statistical difference (p = 0.071). The median TTD was higher in patients whose received IO at 1L (17.0 months vs 7.0 months, p = 0.045). Pneumonitis was the main toxicity being present in 7.1% of patients. Colitis, thyroiditis and hepatitis were seen in one patient each. Conclusions: in general, we were able to observe that in our real-world scenario, IO is well tolerated, regardless of the treatment line. In addition, OS met the findings of the landmark clinical trials.

ARC-4 study: Efficacy and safety of AB928 plus carboplatin, pemetrexed and a PD-1 antibody in participants with metastatic non-small cell lung cancer (mNSCLC).

e21659 Background: Adenosine, derived from ATP released by dying cancer cells in response to chemotherapy, binds to and activates the A2a and A2b receptors on immune cells, resulting in an ineffective anti-tumor immune response. Adenosine receptor blockade may therefore enhance the efficacy of chemotherapy when co-administered with a checkpoint inhibitor. AB928, the first clinical-stage small molecule dual A2aR/ A2bR antagonist, is highly potent and was well tolerated in dose escalation studies as a single agent or in combination with chemo/immunotherapy. Methods: ARC-4 (NCT03846310) is a Phase 1/1b, open-label study in participants (pts) with metastatic, locally advanced, or recurrent non-squamous NSCLC with no alternative or curative therapy option. Pts whose tumor has a genetic alteration for which targeted therapy exists must be chemo/immunotherapy naïve. Pts must have ECOG PS 0-1 and at least one measurable lesion. Two escalating doses of AB928 (75 or 150 mg) administered orally daily were given with standard doses of carboplatin, pemetrexed and pembrolizumab. Results: As of 27Dec19, 7 pts have received AB928 in Ph 1: 75 mg (n = 3), 150 mg (n = 4). Number of prior therapies range from 0 to 6 (median = 3). Most treatment emergent AEs (TEAEs) were Grade 1 or 2, with no Grade 5 events. The most common AEs were anemia, nausea and AST elevation. One pt experienced an SAE (Gr4 thrombocytopenia) that was at least possibly related to AB928. One pt discontinued before assessment due to adverse event (muscle weakness). Of the 6 patients with post-baseline disease assessments, all demonstrated decrease size of target lesion. Three patients (43%) achieved a confirmed partial response: one treatment naïve patient, one patient with EGFRmut disease that had previously progressed on treatment with erlotinib and osimertinib, and one patient who had progressed on therapy with ipilimumab and nivolumab. One additional pt had a > 30% decrease in target lesions and findings consistent with new lesions but opted to continue study treatment. Conclusions: Addition of AB928 to carboplatin, pemetrexed and pembrolizumab did not significantly add to the established safety profile of the standard agents. Combination treatment was associated with disease control in all evaluable pts, including responses in those with PD after TKI and immunotherapy. Expansion is on-going in pts with EGFRmut NSCLC that has failed treatment with TKI. Additional updates on the safety, clinical activity, and correlative biomarker results will be presented. Clinical trial information: 03846310.

First-in-human phase I/II clinical trial of ONC-392: Preserving CTLA-4 immune tolerance checkpoint for safer and more effective cancer immunotherapy.

TPS3159 Background: A major paradigm in cancer immunotherapy is to use checkpoint inhibitors to break regulatory mechanisms that guard the host against autoimmune diseases. CTLA-4-targeting immunotherapy was the first example to establish this paradigm. However, the clinically tested anti-CTLA-4 antibodies exhibit suboptimal efficacy but high toxicity. Our recent studies have demonstrated that immunotherapy-related adverse events (irAE) and the cancer immunotherapeutic effect (CITE) represent distinct and therapeutically separable activities of anti-CTLA-4 antibodies. The irAEs are attributable to inactivation of the CTLA-4 checkpoint, while the CITE is effective through selective depletion of regulatory T cells (Treg) in the tumor microenvironment. We hypothesize that a safer and more effective CTLA-4-targeting immunotherapy should preserve the CTLA-4 checkpoint while enhancing the efficacy and selectivity of Treg-depletion in tumor microenvironment. In preparation to test this ground-breaking hypothesis clinically, we have generated a next generation of anti-CTLA-4 antibody that preserves the CTLA-4 immune checkpoint by avoiding lysosomal degradation of CTLA-4. The new antibody, ONC-392, has dramatically lower irAEs in a humanized mouse model and significantly more potent activity in depleting tumor-infiltrating Tregs, resulting in more effective CITE. Methods: This is an open label Phase IA/IB clinical study to test the safety, pharmacokinetics (PK), and efficacy of ONC-392 as a single agent and in combination with Pembrolizumab in advanced solid tumors and non-small cell lung cancer patients. The study consists of two linked parts: Part A is a dose-finding rapid titration study, with ONC-392 as a single agent in patients with advanced disease of various histology. The aim of this trial is to define the recommended Phase II dose for ONC-392 monotherapy (RP2D-M), Part B is a Phase IA/IB trial of ONC-392 in combination with a standard dose of 200 mg Pembrolizumab in patients with NSCLC. The trial consists of a dose-finding, dose escalation or de-escalation, Phase IA component aimed at defining the recommended phase II dose for ONC-392 in combination with a standard dose of Pembrolizumab (RP2D-C), then progressing into two parallel, single arm, Phase IB expansion cohorts to test for safety and initial efficacy in two groups of patients with NSCLC: Stage IV NSCLC anti-PD(L)1 immunotherapy naïve with PD-L1-positive (PD-L1 TPS ≥ 1%); Stage IV NSCLC refractory/resistant to anti-PD(L)1 immunotherapy. Clinical trial information: NCT04140526 .

A phase I and randomized phase II etctn study of KW-0761 (Mogamulizumab) and MK-3475 (Pembrolizumab) in relapsed and refractory diffuse large B-cell lymphoma.

TPS8072 Background: Diffuse large B-cell lymphoma (DLBCL) escapes host immune responses via inhibition of the B2M and CD58 pathways and upregulation of PD-1 ligands. However, treatment results with PD-1 blockade have been disappointing. One potential mechanism is the recruitment of intra-tumoral regulatory T-cells (Tregs) which suppress anti-tumor immunity and inhibit NK cell cytotoxicity. Targeting regulatory T cells with the CCR4 antibody mogamulizumab (KW-0761) represents a molecularly informed strategy to overcome this resistance. Mogamulizumab has been safely administered in combination with pembrolizumab (MK-3475) in patients with solid malignancies and may promote CD8 T-cell dependent effector and NK cell-dependent cytotoxicity in lymphomas. Methods: This is a multi-center NIH-ETCTN phase Ib/randomized phase II study. The phase I will evaluate the safety and tolerability of mogamulizumab in combination with pembrolizumab in patients with R/R DLBCL and determine the recommended phase II dose (RP2D). A traditional 3+3 design with a starting dose of pembrolizumab 200mg IV on day 1 of a 21-day cycle and mogamulizumab 1mg/kg IV on days 1, 8, 15 and then 1.5 mg/kg IV every 21 days. The phase II will evaluate the efficacy of the combination by PFS (primary endpoint) ORR and CR (secondary endpoints). This will be a randomized 1:1 study with allowed crossover, comparing the combination to single agent pembrolizumab Correlative studies will evaluate the association of tumor infiltrating CD8 and NK cells with response to treatment, somatic mutations in B2M and CD58 and with MHC-I expression on DLBCL cells. Functional characterization of circulating immune cells in the peripheral blood and measurement of pro and anti-inflammatory cytokines will be used to assess the levels, activation status and effector function of Tregs and circulating T cells. Inclusion criteria include measurable disease, ≥2 prior lines of therapy including or ineligible for autologous stem cell transplant, ECOG ≤ 2 and normal organ function. Prior or planned allogeneic stem cell transplant, as well as prior treatment with an anti PD-1/PD-L1/CTLA4 antibody, preexisting autoimmune disease or CNS involvement by lymphoma are exclusion criteria. The study aims to enroll up to 12 patients on the phase I and up to 58 patients on the phase II and can be opened at any ETCTN participating site. To date it has been opened at two sites and is accruing the first patients for the phase I portion. Clinical trial information: NCT03309878 .

First-line pembrolizumab and trastuzumab in HER2-positive oesophageal, gastric, or gastro-oesophageal junction cancer: an open-label, single-arm, phase 2 trial

Addition of trastuzumab to first-line chemotherapy improves overall survival in patients with HER2-positive metastatic gastric cancer. We assessed the safety and activity of pembrolizumab in combination with trastuzumab and chemotherapy in first-line HER2-positive metastatic oesophagogastric (gastric, oesophageal, or gastroesophageal junction) cancer. This study was an investigator-initiated, open-label, non-randomised, single-arm, single centre, phase 2 trial in patients aged 18 years or older with HER2-positive metastatic oesophagogastric cancer. Eligible patients had measurable or evaluable non-measurable disease, Eastern Cooperative Oncology Group performance status of 0, 1, or 2, and left ventricular ejection fraction of at least 53%. Patients were eligible to receive an initial induction cycle of 200 mg flat dose of intravenous pembrolizumab and 8 mg/kg loading dose of intravenous trastuzumab. For subsequent cycles, patients received 130 mg/m2 of intravenous oxaliplatin or 80 mg/m2 of cisplatin on day 1, 850 mg/m2 of oral capecitabine twice a day for 2 weeks followed by 1 week off (or intravenous 5-fluorouracil, 800 mg/m2 per day on days 1-5), and a 200 mg flat dose of intravenous pembrolizumab, and 6 mg/kg of trastuzumab, administered on day 1 of each 3-week cycle. The primary endpoint was 6-month progression-free survival, defined as the proportion of patients alive and free of progression at 6 months, assessed in patients who received at least one dose of trastuzumab and pembrolizumab. The regimen would be considered worthy of further investigation if 26 or more of 37 patients were progression-free at 6 months. This trial is registered with ClinicalTrials.gov, NCT02954536, and is ongoing, but closed to enrolment. Between Nov 11, 2016, and Jan 23, 2019, 37 patients were enrolled. At the time of data cutoff on Aug 6, 2019, median follow-up among survivors was 13·0 months (IQR 11·7-23·5). The primary endpoint was achieved; 26 (70%; 95% CI 54-83) of 37 patients were progression-free at 6 months. The most common treatment-related adverse event of any grade was neuropathy, which was reported in 36 (97%) of 37 patients. The most common grade 3 or 4 adverse events were lymphocytopenia (seven [19%] patients with grade 3 and two [5%] with grade 4), grade 3 decreased electrolytes (six [16%] patients), and grade 3 anaemia (four [11%] patients). Serious adverse events occurred in two patients patients (both grade 3 nephritis leading to treatment discontinuation). Four patients discontinued pembrolizumab because of immune-related adverse events. There were no treatment-related deaths. Pembrolizumab can be safely combined with trastuzumab and chemotherapy and has promising activity in HER2-positive metastatic oesophagogastric cancer. A randomised phase 3 clinical trial assessing the efficacy and safety of pembrolizumab versus placebo in combination with trastuzumab and chemotherapy in first-line HER2-positive metastatic oesophagogastric cancer is underway. Merck & Co.

SAT-485 Variations in the Time Course of Pembrolizumab-Induced Thyroiditis: A Case Series

Variations in the Time Course of Pembrolizumab-Induced Thyroiditis: A Case SeriesIntroduction:Thyroid dysfunction is reported in 5 - 9.5 % of patients treated with Pembrolizumab, one of the PD-1 immune checkpoint inhibitors. However, the underlying mechanism of Pembrolizumab-induced thyroid disorders remains unclear.We present 3 clinical cases with Pembrolizumab-induced painless thyroiditis. They initially presented with thyrotoxicosis, but later converted to hypothyroidism. The onset of thyrotoxicosis after the treatment and time course of changing in thyroid function were varied among these cases. All three cases had normal thyroid function prior to the treatment.Case 1: 63-year-old M with bladder cancer, NSCLC and multiple brain metastases developed overt thyrotoxicosis with TSH 0.02 (0.34 - 4.82 mIU/mL) and Free T4 2.2 (0.8 - 1.5 ng/dL) at 108 days after the first cycle of Pembrolizumab. He had high TgAb (856) and TPO antibodies (196). In 14 days, he converted to hypothyroidism confirmed by TSH 14.6 and Free T4 0.8. Patient was started on Levothyroxine.Case 2: 69-year-old M with Stage IV NSCLC presented with thyrotoxicosis (TSH 0.01, Free T4 1.9) at days 41 after starting Pembrolizumab. TPO antibodies and TgAb were negative. During 51 days of follow up, he converted to hypothyroidism (TSH 8.89 and continued to trend up above 60). He eventually required levothyroxine therapy.Case 3: 57-year-old M with invasive verrucous squamous cell carcinoma of the perineum, urethra and prostate had normal TSH at baseline. Within 39 days after the first dose of pembrolizumab, TSH dropped to 0.013 and Total T4 increased to 14.8 (4.5 - 12.1 ug/dL), consistent with overt hyperthyroidism. In 108 days, patient developed hypothyroidism with Free T4 0.7.Discussion:All 3 cases we present did not have overt signs or symptoms of hyperthyroidism. Thyrotoxicosis spontaneously resolved without requiring steroid treatment. Studies suggest symptomatic treatment of beta blockers in cases of tachycardia, otherwise steroid use is not routinely recommended in PD1-induced thyroiditis.One cohort study analyzed the dynamic course of thyroid functions in patients receiving Pembrolizumab. Among the patients who developed thyrotoxicosis while on PD-1 inhibitor therapy, median onset time was 47 days (14–447 days). The median time for transition from thyrotoxicosis to hypothyroidism was 42 days (21–169 days).Conclusion:Our case series highlight the variations in the time course and nature of the Pembrolizumab-induced thyroiditis. Clinicians should be aware of the relatively short period of fluctuations of thyroid functions in patients treated with PD-1 inhibitors.

SAT-667 Partial Beta-Cell Destruction: An Atypical Case of Immune Checkpoint Inhibitor Diabetes Mellitus

Background: Autoimmune diabetes mellitus (CPI-DM) caused by immune checkpoint inhibitors (CPIs) is rare- occurring in approximately one percent of patients exposed to this form of cancer immunotherapy. Typically, this immune related adverse event occurs after treatment with PD-1/PD-L1 inhibitors. It is characterized by abrupt insulinopenia leading to acute hyperglycemia. Beta cell autoantibodies are positive in approximately half the cases. DKA is common at the time of diagnosis. Recovery of beta cell function has been reported in only two case reports. In one case, spontaneous resolution occurred following cessation of CPI therapy and in the other the patient was treated with infliximab for concurrent inflammatory arthritis prior to resolution of CPI-DM. Clinical Case: A 50-year-old woman was started on adjuvant pembrolizumab for stage IIIC melanoma following surgery. She had no prior history of diabetes mellitus, thyroid disease, or other autoimmune disease. Pre-infusion random blood glucoses (RBG) were 84 - 105 mg/dL. After 36 weeks, she developed hypothyroidism (TSH 17.5 (0.5-4.1 mIU/L), FT4 6 (10-18 ug/dL)) and started levothyroxine. Pembrolizumab was continued. For nine weeks following her diagnosis with CPI- hypothyroidism, her pre-infusion RBG ranged from 102-133. At 45 weeks (15 cycles) after initiating pembrolizumab, her RBG was 260. She was not on glucocorticoids and had no other signs of inflammation or stress. Pembrolizumab was continued. Just prior to her 17th cycle, 48 weeks after initiating adjuvant pembrolizumab, her RBG was 482 with a normal anion gap and HCO3, and her A1c was 8.9%. Her last dose of pembrolizumab was held. She started metformin and liraglutide. In just three weeks, a random c-peptide was inadequate at 1.7 (0.8-3.5 ng/mL) with a recent RBG of 220 and A1c of 10.3%, showing the acuity and extremity of her hyperglycemia. Over the course of the year, she has achieved excellent glucose control (A1c 6.3-7.1) on this regimen with preservation of insulin production (c-peptides 1.4-1.8 with matched RBG 92-129). She never required insulin. Her beta cell autoantibodies are negative. Clinical Lessons: This is a case of CPI-DM in which the patient did not have complete loss of beta-cell function. The acuity of her hyperglycemia is not consistent with new onset type 2 diabetes. At diagnosis, her c-peptide was inadequate suggesting insufficient insulin production rather than insulin resistance. Therefore, her hyperglycemia is more consistent with CPI-DM than type 2 diabetes. Atypically, she did not progress to fulminant beta cell failure, which could have been due to cessation of pembrolizumab (which is not unique to this case), initiation of liraglutide and metformin, or other unknown immunologic responses that inhibited full beta cell loss. This case raises the possibility of preventing fully insulin dependent CPI-DM if hyperglycemia is caught and treated early.

Immune-Related Myocarditis Presenting as Shortness of Breath and Complete Heart Block in an Urothelial Cancer Patient Receiving Pembrolizumab: A Case Report

Pembrolizumab is an immune-checkpoint inhibitor (ICI) drug approved for the treatment of patients who have locally advanced or metastatic urothelial cancer and are not eligible for cisplatin-containing therapy. However, like other antiPD-1s, pembrolizumab can cause immune- related adverse events (irAEs), some of which can be serious enough to warrant emergency care 3-7. Pembrolizumab-related cardiac irAEs, owing to the increased morbidity and mortality associated with them, can present a special challenge in the emergency department. Most documented cardiac irAEs occurred in patients receiving anti-PD-1s in combination with other agents or in patients with pre-existing heart conditions and were easily resolved with steroid treatment8. Herein, we describe a case with unclear symptom presentation in a patient with no previous cardiac history receiving only 1 dose of pembrolizumab. Knowledge gained from this case and others will help elucidate the early- and late-onset toxic effects associated with pembrolizumab and inform the development of effective algorithms for the identification and management of these effects, thereby optimizing the safety of pembrolizumab and other immunotherapy agents in the Emergency Department.

Phase 1 Trial of Pembrolizumab Administered Concurrently With Chemoradiotherapy for Locally Advanced Non–Small Cell Lung Cancer

Consolidative programmed death ligand-1 (PD-L) inhibition after chemoradiotherapy improves overall survival and progression-free survival (PFS) for stage III non-small cell lung cancer (NSCLC) and requires safety evaluation for incorporation of programmed cell death 1 (PD-1) inhibition at the onset of chemoradiotherapy. To determine the safety and tolerability of PD-1 inhibition concurrently with definitive chemoradiotherapy for NSCLC. This phase 1 prospective multicenter nonrandomized controlled trial using a 3 plus 3 design was performed from August 30, 2016, to October 24, 2018, with a median follow-up of 16.0 (95% CI, 12.0-22.6) months and data locked on July 25, 2019. Twenty-one participants had locally advanced, unresectable, stage III NSCLC as determined by multidisciplinary review, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate hematologic, renal, and hepatic function. Data were analyzed from October 17, 2016, to July 19, 2019. Pembrolizumab was combined with concurrent chemoradiotherapy (weekly carboplatin and paclitaxel with 60 Gy of radiation in 2 Gy per d). Dose cohorts evaluated included full-dose pembrolizumab (200 mg intravenously every 3 weeks) 2 to 6 weeks after chemoradiotherapy (cohort 1); reduced-dose pembrolizumab (100 mg intravenously every 3 weeks) starting day 29 of chemoradiotherapy (cohort 2); full-dose pembrolizumab starting day 29 of chemoradiotherapy (cohort 3); reduced-dose pembrolizumab starting day 1 of chemoradiotherapy (cohort 4); and full-dose pembrolizumab starting day 1 of chemoradiotherapy (cohort 5). A safety expansion cohort of 6 patients was planned based on the maximum tolerated dose of pembrolizumab. Dose-limiting toxic effects were defined as pneumonitis of at least grade 4 within cycle 1 of pembrolizumab treatment. Safety and tolerability of PD-1 inhibition with chemoradiotherapy for NSCLC. Secondary outcomes included PFS and pneumonitis rates. Among the 21 patients included in the analysis (11 female [52%]; median age, 69.5 [range, 53.0-85.0] years), no dose-limiting toxic effects in any cohort were observed. One case of grade 5 pneumonitis occurred in the safety expansion cohort with the cohort 5 regimen. Immune-related adverse events of at least grade 3 occurred in 4 patients (18%). Median PFS for patients who received at least 1 dose of pembrolizumab (n = 21) was 18.7 (95% CI, 11.8-29.4) months, and 6- and 12-month PFS were 81.0% (95% CI, 64.1%-97.7%) and 69.7% (95% CI, 49.3%-90.2%), respectively. Median PFS for patients who received at least 2 doses of pembrolizumab (n = 19) was 21.0 (95% CI, 15.3 to infinity) months. These findings suggest that combined treatment with PD-1 inhibitors and chemoradiotherapy for stage III NSCLC is tolerable, with promising PFS of 69.7% at 12 months, and requires further study. ClinicalTrials.gov Identifier: NCT02621398.

Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study.

In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in previously treated, programmed death-ligand 1 (PD-L1)‒expressing advanced non‒small-cell lung cancer (NSCLC) in patients with a tumor proportion score (TPS) ≥ 50% and ≥ 1%. We report KEYNOTE-010 long-term outcomes, including after 35 cycles/2 years or second-course pembrolizumab. Of 1,033 patients randomly assigned (intention to treat), 690 received up to 35 cycles/2 years of pembrolizumab 2 mg/kg (n = 344) or 10 mg/kg (n = 346) every 3 weeks, and 343 received docetaxel 75 mg/m2 every 3 weeks. Eligible patients with disease progression after 35 cycles/2 years of pembrolizumab could receive second-course treatment (up to 17 cycles). Pembrolizumab doses were pooled because no between-dose difference was observed at primary analysis. Pembrolizumab continued to improve OS over docetaxel in the PD-L1 TPS ≥ 50% and ≥ 1% groups (hazard ratio [HR], 0.53; 95% CI, 0.42 to 0.66; P < .00001; and HR, 0.69; 95% CI, 0.60 to 0.80; P < .00001, respectively) after a 42.6-month (range, 35.2-53.2 months) median follow-up. Estimated 36-month OS rates were 34.5% versus 12.7% and 22.9% versus 11.0%, respectively. Grade 3-5 treatment-related adverse events occurred in 16% versus 37% of patients, respectively. Seventy-nine of 690 patients completed 35 cycles/2 years of pembrolizumab; 12-month OS and progression-free survival rates after completing treatment were 98.7% (95% CI, 91.1% to 99.8%) and 72.5% (95% CI, 59.9% to 81.8%), respectively. Seventy-five patients (95%) had objective response (RECIST v1.1, blinded independent central review) and 48 (64%) had ongoing response. Grade 3-5 treatment-related adverse events occurred in 17.7% of patients. Fourteen patients received second-course pembrolizumab: 5 completed 17 cycles, 6 (43%) had partial response, and 5 (36%) had stable disease. Pembrolizumab provided long-term OS benefit over docetaxel, with manageable safety, durable responses among patients receiving 2 years of treatment, and disease control with second-course treatment, further supporting pembrolizumab for previously treated, PD-L1‒expressing advanced NSCLC.

Abstract OT1-01-02: Neoadjuvant pembrolizumab + decitabine followed by standard neoadjuvant chemotherapy for locally advanced HER2-breast cancer

Abstract Background: Higher levels of tumor-infiltrating lymphocytes (TIL) in breast cancers are associated with increased likelihood of pathologic complete response (pCR) to chemotherapy and improved outcomes. DNA methyltransferase inhibitors (DNMTi) can augment immune responses to cancers by upregulating tumor antigen expression, increasing MHC Class I expression and antigen presentation, decreasing numbers and activity of myeloid derived suppressor cells (MDSC) and increasing responsiveness of T lymphocytes. We have shown that decitabine augments the effectiveness of immunotherapy against murine triple negative breast cancer (TNBC). Trial design: Patients with HER-2-negative breast cancer who are candidates for neoadjuvant chemotherapy will receive decitabine (15 mg/kg x 4 doses over 5 days) followed by 2 doses of pembrolizumab (200 mg, 2 weeks apart) prior to starting neoadjuvant chemotherapy. Two research biopsies are obtained - 1 prior to the window immunotherapy and 1 afterwards, prior to starting chemotherapy. Chemotherapy regimens: TNBC - ddAC X 4 followed by weekly Taxol + Carboplatin X 12; HR+ - ddAC X 4 followed by weekly Taxol X 12. After the safely lead-in, the sequence of regimens can be reversed, per treating physician preference. Safety Lead-In: During immunotherapy and dose-dense AC in the first 11 patients enrolled and who have received at least 3 doses of decitabine and at least 1 dose of pembrolizumab, clinically significant immune related adverse events (irAEs) will be reported in an expedited manner. Accrual was halted until the safety lead-in phase was completed. Brief Eligibility criteria: Primary breast cancer, candidates for neoadjuvant chemotherapy Cohort A: TNBC (ER&amp;lt;10%, PR&amp;lt;10%, Her-2 negative) cT2, N1 or N2 cT2, 3-5 cm, N0 Any T3 or T4 Cohort B: ER+ or PR+, Her-2 negative cT2, N1 or N2 Any T3 or T4ECOG status 0-1 No Active autoimmune diseases Absence of metastatic disease too extensive to consider surgery for the primary Specific aims: Primary endpoint: Changes in Lymphocyte infiltration - by 10-15% Tumor area Stromal area Secondary endpoints: Gene expression (Nanostring) Multiplex Cell Markers (DAPI/CD4/CD8/FOXP3/CK/PDL1/PDL2, and MDSCs) pCR Percentage of patients with lymphocyte-predominant breast cancer Correlation of PD-L1 expression with pCR MDSC in blood samples pre- and post- window portion Sample Size and Statistical methods: Cohort A (TNBC) is the primary target group in this trial. When Cohort A has achieved its required sample size of 28 evaluable patients, Cohort B (HR+) will be closed to accrual irrespective of accrual to that cohort. However, in the unlikely event that accrual to Cohort B occurs at a faster rate than in Cohort A, Cohort B will be capped at 18 patients. Therefore, the projected sample size for this study is 32-50 patients. A one-sided paired t-test will be used to compare baseline and post-treatment percentage of tumor and stromal areas with infiltrating lymphocytes. The paired t-test will be applied separately to Cohorts A and B. Present accrual and target accrual: 12 subjects have been accrued; 1 withdrew prior to any protocol therapy. The 11 patient safety lead-in has been completed. As described above, the projected total sample size is 32-50 patients. Citation Format: Harry Douglas Bear, Michael O. Idowu, Andrew Poklepovic, Adam Sima, Maciej Kmieciak. Neoadjuvant pembrolizumab + decitabine followed by standard neoadjuvant chemotherapy for locally advanced HER2-breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-01-02.

Abstract P3-09-17: Preoperative pembrolizumab increases sTILs in treatment naïve stage I/IIA TNBC patients in a window of opportunity trial

Abstract Background: High levels of stromal tumor-infiltrating lymphocytes (sTILs) are significantly associated with chemosensitivity and improved overall survival for patients with triple negative breast cancer (TNBC). Our aim is to determine if we can significantly increase sTILs from biopsy to lumpectomy in a presurgical window of opportunity trial with pembrolizumab and intraoperaperative radiation (IORT) in treatment-naïve early stage TNBC compared to matched IORT only controls. We also evaluate the changes in the spatial distribution of intraepithelial TILs (iTILs) by utilizing a deep learning algorithm. Our secondary aim is to characterize the tumor immune microenvironment (TME) using quantitative multiplex immunofluorescence (qmIF) and transcriptomic analysis of tumor-associated and immune genes. Methods: Seven women with node negative TNBC &amp;lt;2.5 cm were enrolled in either our presurgical trial with pembrolizumab and IORT as an upfront boost (NCT02977468) or a parallel study with IORT alone (NCT03165487). The treatment consisted of two doses of pre-operative pembrolizumab (200mg IV) given alone with the second dose -10 to -18 days from surgery; 20Gy IORT was delivered during surgery to the lumpectomy bed. All patients completed standard of care adjuvant chemotherapy and whole breast irradiation. Initial analyses performed include assessments of sTILs and iTILs on H&amp;E sections from the initial biopsy and lumpectomy. iTILs were identified with a deep learning algorithm in pathologist annotated regions with invasive carcinoma, excluding in situ legions. Deep learning derived percentages of iTILs were validated through comparison with manual estimates performed by a pathologist per international guidelines. Spatial clustering analysis with iTILs was performed by calculating the Ball-Hall index for each case to measure the mean dispersion through all the clusters. Results: Seven patients were enrolled between Nov 2017-Apr 2019; 3 patients received pembrolizumab+IORT; and 4 patients received IORT alone. Initial pathology assessment of sTILs demonstrated no significant change between biopsy and lumpectomy in control patients. No consistent patterns of iTILs dispersion were observed in the control patients. Out of the 3 pembrolizumab treated patients, one patient demonstrated a marked increase in sTILs (20% to 60%) with a shift from a neutrophil rich to lymphoplasmacytic stromal infiltrate where the mean dispersion of the iTILs doubled (180 to 360). In the other 2 pembrolizumab patients, one remained stable and one showed a slight increase in sTILs. The iTILs dispersion increased significantly in these patients (from 40 to 90 and 10 to 280, respectively). A corresponding spatial analysis of sTILs is ongoing. Additionally, qmIF and transcriptomic analysis of tumor-associated and immune genes is currently underway to compare biopsy and surgical specimens. Conclusion: In this preliminary analysis, we observe preoperative pembrolizumab-induced increases in sTILs with increased mean dispersion of iTILs in treatment naïve TNBC. Our initial analysis in this ongoing trial appears promising after examining changes in both the density and spatial structure of TILs. Further investigation is warranted to elucidate the impact of preoperative pembrolizumab in the TME of early stage TNBC and other potential therapeutic implications. Citation Format: Rami Vanguri, Hua Guo, Shuobo Boboila, Tahsin Kurc, Han Le, Shahira Abousamra, Le Hou, Dimitris Samaras, Rajarsi Gupta, Joel Saltz, Kevin Gardner, Hanina Hibshoosh, Kevin Kalinsky, Eileen Connolly. Preoperative pembrolizumab increases sTILs in treatment naïve stage I/IIA TNBC patients in a window of opportunity trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-09-17.

Safety of Influenza Vaccine in Patients With Cancer Receiving Pembrolizumab.

There is a concern that influenza vaccination could increase the incidence of immune-related adverse events (irAEs) in patients with cancer receiving immune checkpoint inhibitors. The aim of our study was to determine the safety of influenza vaccination in this patient population. We retrospectively identified patients who received at least 1 dose of pembrolizumab during any influenza season from September 2014 to August 2017 and reviewed medical records for irAEs. The primary endpoint was the incidence of irAEs. We used multivariable logistic regression and cumulative incidence curve with competing risks for comparison. Among 162 patients with cancer included in this study, 70 patients (43.2%) received at least 1 influenza vaccination. The vaccinated group was significantly older (P = .002) and received more cycles of pembrolizumab (P = .006). The incidence of any grade irAEs in the vaccinated group trended toward being lower (25.7% v 40.2%; P = .07) compared with the nonvaccinated group. Influenza vaccination was independently associated with fewer irAEs, with an odds ratio of 0.4 (95% CI, 0.2 to 0.9; P = .03) in multivariable analyses. The vaccinated group was less likely to have irAEs compared with the nonvaccinated group (24.7% v 34.4% at 12 months; P = .05), with death as a competing risk. The median irAE-free duration in the vaccinated group was longer than the nonvaccinated group (not reached v 28 months; P = .037). Influenza vaccination in patients with cancer receiving immune checkpoint inhibitor therapy was not associated with increased irAEs. This supports the safety of influenza vaccination in this patient population.

A phase II study to evaluate safety and efficacy of neoadjuvant pembrolizumab and radiotherapy in localized MSS rectal cancer.

TPS272 Background: Locally advanced rectal cancer remains a clinical challenge with few improvements noted over the past few decades. Although immunotherapy has no current clinical role in microsatellite stable (MSS) colorectal cancer, preclinical models suggest that radiotherapy (RT) can enhance neoantigen presentation, modulate the microenvironment, and improve the likelihood of anti-tumor activity with checkpoint inhibitors use. This prospective phase II trial will test that hypothesis in addition to confirming safety of this approach using a “window-of-opportunity” study design with the anti-PD-1 agent Pembrolizumab. Methods: This monocentric phase II trial, will enroll patients (pts) with rectal cancer who are undergoing neoadjuvant short course RT (scRT) (25 Gy in 5 fractions). according to the standard of care. Eligible includes pts with MSS stage II-III rectal cancer with adequate organ function and availability of pre-treatment tumor, who are undergoing scRT with intention to proceed to surgical resection. Standard ineligibility criteria include active infections, systemic steroid use, or other conditions making immunotherapy use unsafe. Treatment includes 4 doses of Pembrolizumab (200mg IV, once every 3 wks), the first dose being given before the first scRT fraction. Surgery will be performed within 12-16 weeks of the final scRT dose. Primary endpoint is tumor regression grade (TRG) using the Mandard regression grade score targeting a 30% pathological complete response (pCR) compared to 10% in historical controls. Secondary endpoints include OS, DFS, toxicity, local and distant relapse-free survival, negative surgical margins, QoL, quality of surgery and exploratory assessments of tumor infiltrating lymphocytes, profiling of circulating immune cell populations, and molecular predictors of response. A safety stopping rule is planned based on Wald’s sequential probability ratio test for the occurrence of the safety outcome. Enrollment target is 25 pts. Support: MSD. Clinical trial information: NCT04109755 .

Economics of alternative dosing strategies for pembrolizumab and nivolumab at a single academic cancer center.

BackgroundThe FDA initially approved pembrolizumab and nivolumab for doses based on patient weight, but subsequently amended approval to fixed doses. We estimated savings from novel dosing strategies based on real‐world patient data from a single cancer center.MethodsWe analyzed all outpatient doses of pembrolizumab and nivolumab administered at three infusion centers affiliated with our academic hospital between July 1, 2018 and Oct 31, 2018. We estimated savings from several dosing strategies with and without vial sharing between patients.ResultsA total of 1029 doses of pembrolizumab or nivolumab were administered for multiple cancer types. For 77% of doses, the weight‐based dose was less than the fixed dose. “Dose‐minimization” (DM), defined as the lesser of weight‐based and fixed dose decreased nivolumab spending by 9% without affecting pembrolizumab spending. DM plus vial sharing decreased pembrolizumab spending by 19% without affecting nivolumab. The differences in savings were due to availability of multiple vial sizes for nivolumab but not pembrolizumab. DM plus vial sharing for both drugs would have saved $1.5 million USD over the 4‐month study period.ConclusionNew dosing strategies for pembrolizumab and nivolumab can generate large savings without anticipated decrease in efficacy. Barriers include FDA dosing labels, hospital policies against vial sharing, and inaccessibility of smaller vial sizes, which are currently available in other worldwide markets.

Open-Label Pilot Study of Genetically Engineered NY-ESO-1 Specific T Cells (GSK3377794) Alone or in Combination with Pembrolizumab in Relapsed and Refractory Multiple Myeloma

Introduction NY-ESO-1 TCR T (GSK3377794) are autologous polyclonal T cells transduced by a self-inactivating lentiviral vector to express an affinity-enhanced TCR recognizing NY-ESO-1 or LAGE-1a antigenic peptides in complex with HLA-A2. NY-ESO-1 and LAGE-1a are immunogenic cancer/testis antigens overexpressed in mutiple myeloma (MM) and linked to poor clinical outcome. Patients (pts) with MM who received GSK3377794 after autologous stem cell transplant (ASCT) showed encouraging clinical activity. PD-1 expression on CD8 T cells can occur in GSK3377794-treated MM pts and may limit adaptive immune response; this is a mechanism of resistance/relapse in CD19 CAR T-cell trials. Combining GSK3377794 with an anti-PD1 inhibitor (pembrolizumab) may have synergistic antitumor activity. Objective Evaluate safety and efficacy of GSK3377794 alone or in combination with pembrolizumab in pts with relapsed MM. Methods This is an open-label, pilot study (NCT03168438) of GSK3377794 in pts who are HLA-A*02:01, 05, ± 06 positive and have NY-ESO-1+/LAGE-1a+ relapsed/refractory MM. Twenty pts who have received ≥3 prior therapies containing ≥1 (separately or combined; including ASCT) of an IMiD, PI, alkylator, CD38 monoclonal antibody, and glucocorticoid, will be assigned to 1 of 2 arms: GSK3377794 as a single infusion (Arm 1, n=10) or GSK3377794 as a single infusion + pembrolizumab 200 mg IV every 3 wk (Arm 2, n=10). Arm 1 enrollment will complete before enrolling Arm 2. Pembrolizumab treatment will start from Wk 3 (Wk 6 if precluded by toxicity). Each patient will undergo leukapheresis to obtain cells for autologous NY-ESO-1-specific T-cell manufacturing, followed by lymphodepleting chemotherapy with fludarabine + cyclophosphamide, then GSK3377794 infusion of 1−8 × 109 transduced T cells. Study objectives are to assess safety and tolerability (primary) and antitumor activity (secondary) of GSK3377794 treatment (± pembrolizumab). At each visit, pts will be monitored for AEs and treatment-limiting toxicities, efficacy (using IMWG criteria), and biomarkers. Arm 2 enrollment will pause for a 3-wk safety review period after the first 3 pts receive their first pembrolizumab dose. Treatment will continue until disease progression or 108 wk after GSK3377794 infusion. After completing treatment, pts will transfer to long-term follow-up (NCT03391778) to continue safety/survival monitoring for up to 15 years. As of Jan 27, 2019, 50 pts have been screened. Half have tested positive for HLA-A*02:01, 05, ± 06; bone marrow samples from 12/21 (57%) tested positive for NY-ESO-1 ± LAGE-1a. To date, 3 pts have received GSK3377794. Further work is ongoing to enhance patient eligibility. These data are presented on behalf of the original authors with their permission. A similar presentation will be presented at the ASH Annual Meeting, Orlando, FL, USA, Dec 7-10, 2019. This study (NCT03168438) is funded by GSK.