Efficacy Of Pembrolizumab In Combination Research Articles

Exploring the Efficacy of Pembrolizumab in Combination with Carboplatin and Weekly Paclitaxel for Frail Patients with Advanced Non-Small-Cell Lung Cancer: A Key Investigative Study.

Immune checkpoint blockers have revolutionized the first-line treatment of advanced non-small-cell lung cancer (NSCLC). Pembrolizumab, an anti-PD-1 monoclonal antibody, is a standard therapy either alone or in combination with chemotherapy (chemo-IO). The current study explores the efficacy and safety of pembrolizumab with carboplatin and weekly paclitaxel in a cohort of frail patients. A monocentric retrospective study was conducted between 22 September 2020 and 19 January 2023 regarding patients with stage IV NSCLC treated with chemo-IO combination: carboplatin (AUC 5 mg/mL/min; Q4W), weekly paclitaxel (90 mg/m2 on days 1, 8, and 15), and pembrolizumab (200 mg Q4W). The primary objective was real-world progression-free survival (rwPFS). Secondary objectives were overall survival (OS), toxicity profile, and outcomes based on histological subtype. A total of 34 patients (20 squamous and 14 non-squamous NSCLC) benefited from the chemo-IO regimen for frail patients; 41.9% had an ECOG-PS = 2. The median age was 75.5 years. We observed an overall response rate (ORR) of 55.9%. Notably, squamous NSCLC exhibited a significantly higher ORR (80%) than non-squamous NSCLC (21.4%); p = 0.001. The median rw-PFS was 10.6 months (95% CI [6.0, NA]), with 6- and 12-month rw-PFS rates of 69% and 45.8%, respectively. The median OS was not reached, with 12- and 18-month OS rates of 75.6% and 61.4%, respectively. The median number of maintenance cycles of pembrolizumab was 5 (0; 27). Nine patients (26.5%) experienced a toxicity related to chemotherapy leading to a reduction of the dose administered and, in five patients (14.7%), to the permanent discontinuation of chemotherapy. Six patients (17.6%) had an immune-related adverse event leading to the discontinuation of immunotherapy. Pembrolizumab plus carboplatin and weekly paclitaxel demonstrates promising efficacy and safety in frail patients with metastatic NSCLC, especially for ORR in sq-NSCLC. Prospective studies focusing on frail populations are warranted in order to validate these findings and optimize therapeutic strategies in the first-line setting.

Efficacy of pembrolizumab in combination with bevacizumab and oral metronomic cyclophosphamide in the treatment of platinum resistant recurrent ovarian cancer: A retrospective observational study (2180)

Efficacy of pembrolizumab in combination with bevacizumab and oral metronomic cyclophosphamide in the treatment of platinum resistant recurrent ovarian cancer: A retrospective observational study (2180)

Phase II basket trial evaluating the efficacy of pembrolizumab (PE) combined with vorinostat (VO) in patients (pts) with recurrent and/or metastatic squamous cell carcinoma (SCC).

2597 Background: Epigenetic modulation plays a major role in escaping tumor immunosurveillance and confers resistance to immune checkpoint inhibitors. Preclinical evidence suggests that modulating the epigenome might improve the efficacy of immunotherapy. Patients and Methods: PEVOsq is an open-label, non-randomized, multi-center, basket phase II trial, evaluating the efficacy of pembrolizumab in combination with vorinostat in patients with recurrent and/or metastatic squamous cell carcinoma of the cervix, head and neck, anus, vulva/vagina, penis, and lung. Patients had to be PD1/PD-L1 antagonist-naïve. There was no selection based on PD-L1 expression nor on HPV status, and no restriction in terms of prior lines of treatments. Pembrolizumab dose was 200 mg Q3W IV, and vorinostat 400 mg QD PO. Sample size was determined for each cohort using an A’Hern design. Primary endpoint was objective response rate (ORR) according to RECISTv1.1. Secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), and duration of response (DOR). Results: Among 112 included patients, 111 were evaluable for safety and 107 for efficacy. The lung cohort was closed prematurely because of lack of enrollment. Median age was 61 years old [range: 18-85] and the median number of prior lines of therapies was 1 [range: 0-4]. ORR, PFS, G3/4 treatment related adverse events (TRAE), and OS are reported. 28 patients (26%) had an objective response and median DOR was 9.7 months [95%CI: 3.1-15.2]. Results per PD-L1 status will be presented at the meeting. Pembrolizumab and vorinostat were stopped for toxicity in 9% and 39% of patients, respectively. 60% of patients had a dose-reduced of vorinostat for toxicity. Pembrolizumab safety was as expected. Main vorinostat toxicities included hematological toxicity, gastrointestinal disorders, and asthenia and creatinine increase. Conclusions: Pembrolizumab combined with vorinostat showed encouraging antitumor activity in squamous cell carcinoma with unselected PD1/PD-L1 status, especially in cervical and anal cancer, although vorinostat dose had to be reduced because of toxicity in a substantial proportion of patients. Clinical trial information: NCT04357873 . [Table: see text]

Pembrolizumab in combination with bevacizumab and oral cyclophosphamide in heavily pre-treated platinum-resistant ovarian cancer

ObjectiveImmune checkpoint inhibitors have been widely implemented in the treatment of solid tumors. Combinations of immune checkpoint inhibitors with chemotherapy, anti-vascular endothelial growth factor (VEGF) compounds, and poly-adenosine diphosphate-ribose polymerase...

Pembrowm: Results of a Multi-Centre Phase II Trial Investigating the Safety and Efficacy of Rituximab and Pembrolizumab in Relapsed/Refractory Waldenström's Macroglobulinaemia

Background Waldenström's macroglobulinemia (WM) is a rare low grade B-cell NHL, with generally excellent outcomes underpinned by treatment with Rituximab combination therapies and covalent BTK inhibitors (cBTKi). However, these options are not curative and there are very little data to guide treatment options or a clear understanding of prognosis of relapsed/refractory (R/R) WM post cBTKi. PD-1 inhibition has been shown to be highly effective in classical Hodgkin lymphoma, and soluble PD-1 ligands have been implicated in T-cell regulatory function in the WM microenvironment. There is therefore a clear rationale to investigate the efficacy of PD-1 blockade in WM. Aim To determine the safety, tolerability and efficacy of pembrolizumab in combination with rituximab for the treatment of relapsed/refractory WM following prior cBTKi exposure. Methods PembroWM is a phase II, non-randomised, single arm, open label NCRI UK-wide study (NCT03630042) enrolling patients (pts) with R/R WM who had received 1 or more prior lines of treatment, who were not refractory to rituximab based therapy (progressing on or relapsing within 6 months of a rituximab containing regimen). Eligible pts accross 6 sites received rituximab 375mg/m2 weekly for 4 weeks, then 3 monthly (total of 8 doses) and pembrolizumab 200mg IV on a 3-weekly cycle, for a maximum of 18 cycles. The primary end point was the percentage of pts achieving an overall response rate (ORR) of greater than 25% reduction in serum IgM at 24 weeks post treatment. Secondary end points included safety and tolerability, response rates (CR/VGPR) , progression free survival (PFS) and overall survival (OS) at 1 year. Disease response was assessed with serum paraprotein/immunofixation, BM and CT imaging at 24 weeks and 1 year using the International Working Group for WM response criteria. The trial required recruitment of 42 patients with a 55% response rate to meet the primary end point. The trial closed early due to low recruitment rate with a total of 17 patients with a revised response requirement of 9 patients to meet primary end point. Results 17 patients were registered with median age of 70 years (range 43-84), 83% were male, 94% had a PS of 0-1, and the median number of lines of previous treatment was 3 (range 1-6). The majority of patients had a cBTKi as their last treatment prior to enrollment (only 2 patients were BTK naïve). 8 patients were positive for the MYD88 L265P mutation, and 4 patients had mutations in BTKC481. Median IgM levels were 40 g/L (range 2.5-72g/L) with 53% of patients exhibiting WM cells in bone marrow and extra nodal disease in 6%. Median follow up is 15.1 months (0.5 - 24.9). ORR at 24 weeks post treatment was 47.1% (60% CI 34.5-60%) with 6% attaining VGPR, 18% PR, 18% MR and in 6% response was unavailable but there was evidence of MR at week 12. 47% were non-responders; 35% progressed, 12% had stable disease and one patient withdrew during cycle 1 so was non-evaluable. ORR at 52 weeks post treatment was 36.4% (95% CI 10.9-69.2%) with 9% obtaining a VGPR, 27% PR and nil achieving CR. Median PFS was 12.6 months (95% CI 3-n/a) and median OS was not reached. 5 patients completed 18 cycles of treatment. 6 progressed, 3 withdrew due to AE, 2 withdrew consent and one withdrew to an unrelated clinician decision. The AE leading to withdrawal were immune thrombocytopenia (one), and infection in the other two (including one COVID-19 infection) The majority of adverse events were grade 1-2 with the commonest events involving anaemia (29%), fever (29%), infusion related reactions (35%) and raised creatinine (29%)., There were only 2 grade 3 infections. 1 patient experienced an embolic stroke and 1 patient died from respiratory failure; both events were considered unrelated to treatment. Conclusions PEMBROWM is the first study to investigate checkpoint inhibition in WM, and demonstrates the safety and tolerability of the combination of pembrolizumab and rituximab, with encouraging efficacy in a heavily pre-treated population. The recruitment challenges highlighted the combination of reduction in research activity during the COVID-19 pandemic, the difficulties of recruiting to an investigator-led study in a rare indication and the timing of availability/effectiveness of cBTKi in WM in the United Kingdom. A randomised study would be required to evaluate the additional benefit that PD-1 blockade is adding to rituximab monotherapy in a highly relapsed/refractory patient population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

230MO Pembrolizumab plus anlotinib as first-line treatment in patients of CPS≥1 with recurrent or metastatic head and neck squamous-cell carcinoma: A prospective phase II study

At present, pembrolizumab is the first-line standard treatment for recurrent/ metastatic head and neck squamous cell carcinoma(R/M HNSCC). According to existing studies, it is found that the combination of multi-target kinase inhibitor and pembrolizumab has a good objective response rate. There is great need to explore the efficacy of pembrolizumab in combination with anlotinib in the first-line treatment for patients with R/M HNSCC.

343P Immunotherapy as first-line treatment in metastatic non-small cell lung cancer: A single center experience

Immunotherapy has revolutionized treatment in metastatic non small cell lung cancer (NSCLC) without driver mutation.In our study we evaluated the efficacy of pembrolizumab in combination with chemotherapy as first line therapy in advanced NSCLC.

Phase II study of pembrolizumab plus capecitabine and bevacizumab in microsatellite stable (MSS) metastatic colorectal cancer (mCRC).

3565 Background: MSS mCRC rarely responds to pembrolizumab monotherapy, but capecitabine and bevacizumab may induce immune-stimulatory effects. This study evaluates the safety, tolerability and preliminary efficacy of pembrolizumab in combination with capecitabine and bevacizumab in MSS mCRC. Methods: Single-center, phase 2 trial with safety lead-in to confirm the recommended phase 2 dose (RP2D) for capecitabine and expansion cohorts (NCT03396926). Key eligibility: MSS mCRC with stable disease (SD) or progressive disease (PD) on prior fluoropyrimidine-based therapy. Treatment: Capecitabine 1000 mg/m2 PO BID D1-14 Q21 days (confirmed RP2D) plus pembrolizumab 200 mg IV D1 Q21 days and bevacizumab 7.5 mg/kg IV D1 Q21 days. Endpoints: Primary: Objective response rate (ORR) by RECIST 1.1. Key secondary: Safety, duration of response (DOR), progression-free survival (PFS), overall survival (OS). Results: From 04/2018-10/2021, 44 patients (pts) were enrolled. Overall: Median age 53 years (range 28-79); female 50%; Caucasian 61%. Liver metastases at enrollment 80%. Prior therapies: median prior lines of therapy 2 (range 1-5); PD on fluoropyrimidine-containing regimens 91%; prior exposure to bevacizumab 86%. Complete toxicity data are available for 36 off-treatment pts. Grade ≥ 3 treatment-related (tr)AEs occurred in 10 (28%) pts, including grade 3 immune-related AEs in 4 (11%) pts. All-cause serious (s)AEs occurred in 13 (36%) pts and trSAEs in 5 (14%) pts. (tr)AEs leading to dose interruptions, reductions, or delays occurred in 21 (58%) pts, most commonly palmar-plantar erythrodysesthesia syndrome in 17 (47%) pts. Disposition: of 44 pts enrolled, 35 were removed for PD and 1 was removed for treatment noncompliance; 8 treatment ongoing. ORR in 40 evaluable pts was 5% (95% CI: 0.6,16.9). Best response by RECIST 1.1: partial response (PR) in 2 (5%); SD in 26 (65%); PD in 12 (30%). 2 responders: DOR 12 and 15 months, both with liver metastases. Median follow up was 7 months (range 1-45), with median PFS 4.3 months (95% CI: 3.9, 6.1), PFS at 6 months 31.1% (95% CI: 19.2%, 50.4%), and median OS 9.6 months (95% CI: 6.2, 13). Median time on treatment was 5 months (range 1-26). Single cell RNA sequencing on a subset of paired pre- and on-treatment biopsies demonstrated changes in the frequency of dendritic cells. Conclusions: The combination of pembrolizumab with capecitabine and bevacizumab was found to be tolerable with an expected toxicity profile in MSS mCRC pts. The ORR of 5% did not meet the prespecified target of ≥ 15%, however nearly a third of pts had PFS > 6 months. Immune profiling of tumor biopsies and peripheral blood is ongoing. Clinical trial information: NCT03396926.

OA09.03 Pembrolizumab in Combination With Platinum-Based Chemotherapy in Recurrent EGFR/ALK-Positive Non-Small Cell Lung Cancer (NSCLC)

Efficacy of single-agent immune checkpoint inhibitors is limited in patients with EGFR/ALK-altered NSCLC. We conducted a phase II study to assess the efficacy of pembrolizumab in combination with carboplatin and pemetrexed in these patients. Patients with recurrent EGFR-mutated or ALK-rearranged NSCLC, previously treated with targeted therapy, were eligible. Patients were treated with carboplatin AUC5, pemetrexed 500 mg/m2 and pembrolizumab 200 mg I.V. every 3 weeks. After 4 cycles patients were maintained on pemetrexed and pembrolizumab for up to 2 years. Disease was assessed every 2 cycles for the first 6 cycles, then per investigator discretion. The primary end-point was RECIST 1.1 defined response rate. Secondary endpoints included PFS and OS. Tumor PD-L1 expression was assessed locally. Blood for circulating tumor cells (CTCs) was collected prior to the 1st and 3rd cycles. The plan was to enroll 28 evaluable patients in each of two separate cohorts of EGFR-mutated and ALK-rearranged NSCLC. Slow enrollment led to early termination of the trial. Of the 33 patients enrolled, 26 had EGFR-mutated NSCLC (13 del19, 9 L858R), 64% were female and median age was 67 years. The median number of prior treatments was 1 (range 1-3). 22 of 26 EGFR+ NSCLC patients had received prior osimertinib. Median number of cycles was 6 (2-24 cycles), with 4 patients, all EGFR+, still on therapy. Response rates (95%CI) were 42% (23%, 63%) and 29% (4%, 71%) among EGFR+ and ALK+ patients, respectively. Median duration of response was 6.1 months in all patients and in EGFR+ patients. Other efficacy results are provided below. Tumor PD-L1 expression was available for 30 patients and was ≥ 1% in 17. There was no difference in survival between patients with tumor PD-L1 <1% vs. ≥ 1%. The median CTC count at baseline in 15 EGFR+ patients in whom samples were available was 4/ml (0-23). Median overall survival among EGFR+ patients with decreased vs. increased CTC count during treatment was not reached vs. 18.5 months, respectively (p=0.52 for OS). The most common adverse events were fatigue, nausea, cytopenias, cough and dyspnea. The most common ≥ grade 3 toxicities were neutropenia, thrombocytopenia, thromboembolism, and AST/ALT elevation. One patient developed pneumonitis.TableEFGR+ (n=26)ALK+ (n=7)All (n=33)Median PFS (months. 95%CI)8.3 (7.2, 16.5)2.9 (1.1, NE)7.3 (5.3, 14.1)12-month PFS (95% CI)29% (14%, 59%)14% (2%, 88%)26% (13%, 50%)Median OS (months, 95% CI)22.2 (20.6, NE)2.9 (1.1, NE)20.6 (10.1, NE)12-month OS (95% CI)76% (59%, 97%)14% (2%, 88%)61% (44%, 83%) Open table in a new tab Pembrolizumab in combination with chemotherapy demonstrated a response rate of 42% and median survival of 22 months among patients with recurrent EGFR-mutated NSCLC. These results warrant further study of this combination in this patient population.

Phase II study of pembrolizumab plus capecitabine and bevacizumab in microsatellite stable (MSS) metastatic colorectal cancer (mCRC): Interim analysis.

77 Background: MSS mCRC rarely responds to pembrolizumab monotherapy, but capecitabine and bevacizumab may induce immune-stimulatory effects. This study evaluates the safety, tolerability and preliminary efficacy of pembrolizumab in combination with capecitabine and bevacizumab in MSS mCRC. We present results at the planned interim analysis. Methods: Design:single-arm, open-label, single-site phase 2 trial with a safety lead-in to confirm the recommended phase 2 dose (RP2D) for capecitabine and expansion cohorts. Per the Simon’s 2-stage design, ≤1 response in 29 patients (pts) requires trial suspension. Key eligibility criteria: MSS mCRC with stable disease (SD) or progressive disease (PD) on prior fluoropyrimidine-based therapy. Treatment: RP2D PO capecitabine on days 1-14 plus 200 mg IV pembrolizumab and 7.5 mg/kg IV bevacizumab on day 1 in 21-day cycles. Pts are followed for toxicity and radiographic response. Results: From 04/2018-09/2020, 29 pts were enrolled, of whom 15 (52%) were female; 21 (72%) white; and median age was 55 years (range 36-77 years). Prior therapies: 2 (7%) pts had SD and 27 (93%) pts had PD on fluoropyrimidine-containing regimens; 24 (83%) pts had prior exposure to bevacizumab. The RP2D for capecitabine was 1000 mg/m2 PO BID, with no dose limiting toxicities observed. Complete toxicity data are available for 25 off-treatment pts. The most common related adverse events (AEs) were palmar-plantar erythrodysesthesia (PPE) (64%) and fatigue (68%). Grade ≥3 related AEs occurred in 9 (36%) pts, including immune-related AEs of Grade 3 dyspnea, hypophosphatemia, and pancreatitis in 1 pt each. Treatment related AEs leading to dose interruptions, reductions, or delays occurred in 15 (60%) pts, most commonly PPE in 13 (52%) pts. No pt had a related AE leading to treatment discontinuation or death. Disposition: of 29 pts enrolled, 24 were removed for PD and 1 was removed for an unrelated AE. Best response by RECIST 1.1 in 23 evaluable pts: partial response (PR) in 2 (9%); SD in 14 (61%); PD in 7 (30%). Median time on treatment was 6 months (range 2-26 months). Conclusions: Combination of pembrolizumab with capecitabine and bevacizumab was found to be tolerable with an expected toxicity profile in MSS mCRC pts. With 2 responses, the study met interim analysis criteria to continue accrual. Tissue and blood-based immune correlatives are planned. Clinical trial information: NCT03396926.

Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C)

Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C)

Safety and efficacy of pembrolizumab in combination with S-1 plus oxaliplatin as a first-line treatment in patients with advanced gastric/gastroesophageal junction cancer: Cohort 1 data from the KEYNOTE-659 phase IIb study

AimThe KEYNOTE-659 study evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy as the first-line treatment in Japanese patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer. In this paper, we report results from cohort 1 (S-1 plus oxaliplatin [SOX] with pembrolizumab). MethodsThis was a non-randomised, multicentre, open-label phase IIb study in patients with advanced programmed death-ligand 1 (PD-L1)-positive, human epidermal growth factor receptor 2-negative G/GEJ tumours. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Exploratory analyses were performed based on the PD-L1 combined positive score (CPS) status. ResultsFifty-four patients were evaluated. The median follow-up was 10.1 months. ORR and DCR by BICR were 72.2% (95% confidence interval [CI] 58.4–83.5) and 96.3% (95% CI 87.3–99.5), respectively. Median DOR, TTR, PFS and OS were as follows: not reached, 1.5 months, 9.4 months and not reached. The ORR was 73.9% in patients with CPS ≥1 to <10 and 71.0% in those with CPS ≥10. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 57.4% of patients. The most common grade ≥3 TRAEs were decreased platelet count (14.8%), decreased neutrophil count (13.0%), colitis (5.6%) and adrenal insufficiency (5.6%). ConclusionsSOX with pembrolizumab showed encouraging efficacy and a manageable safety profile for the first-line treatment of advanced G/GEJ cancer. Trial registrationNCT03382600/JapicCTI-183829.

Phase II study of the combination of abemaciclib and pembrolizumab in locally advanced unresectable or metastatic gastroesophageal adenocarcinoma: Big Ten Cancer Research Consortium BTCRC-GI18-149.

TPS461 Background: Metastatic gastroesophageal adenocarcinoma (GEA) has poor prognosis. Overall survival (OS) remains around 12 months (mo) with current therapies. Pembrolizumab is approved for advanced GEA that has progressed on at least 2 prior lines of systemic therapy. However, the majority of patients progress on this treatment, and less than 15% of patients experience objective response (OR). This study will evaluate efficacy of pembrolizumab in combination with cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, abemaciclib, in patients with advanced GEA. Preclinical studies have demonstrated that CDK4/6 inhibitors can increase anti-tumor immunity and can synergize with immune checkpoint inhibitors. Based on these data, we hypothesize that abemaciclib will augment response to pembrolizumab in GEA. Methods: This is a multi-institutional, single arm, open label, phase II study of abemaciclib in combination with pembrolizumab in patients with advanced GEA who have progressed or were intolerant to at least 2 prior lines of therapy. Patients previously treated with immune checkpoint inhibitors or with microsattelite unstable tumors will be excluded. Treatments will be given on a 21 day cycle until disease progression or intolerable toxicities. Pembrolizumab, 200 mg intravenously, will be given on day 1, and abemaciclib, 150 mg, will be taken orally twice a day on days 1-21. Primary endpoint is progression free survival (PFS). Secondary endpoints include PFS rate at 6 mo, disease control rate, OS and OR rate. Correlative endpoints will examine relationship between PDL1 status, genomic signature and treatment response. Saliva samples will be collected for microbiome analysis. Archival tumor tissue and blood samples will be banked for future studies. A total of 31 evaluable subjects will be enrolled to detect an anticipated increase in the median PFS from 2 months (null hypothesis) to 4 months with 80% power at the one-sided 0.05 significance level. The trial is open to enrollment. Clinical trial information: NCT03997448.

Abstract CT152: A phase II study of pembrolizumab and eribulin in patients with HR-positive/HER2-negative metastatic breast cancer previously treated with anthracyclines and taxanes (KELLY study)

Abstract BACKGROUND: Preliminary results with MK3475 (pembrolizumab) in heavily pretreated Estrogen Receptor (ER)-positive/ Human Epidermal Growth Factor Receptor 2 (HER2)-negative metastatic breast cancer (MBC) patients have shown promising antitumor activity. However, no data are available with anti-Programmed Death-Ligand 1 (PD-L1) agents in combination with chemotherapy in this tumor subtype in the metastatic setting. The aim of this trial is to evaluate the efficacy of pembrolizumab in combination with eribulin in patients with Hormone Receptor (HR)-positive/HER2-negative MBC who have been previously treated with an anthracycline and a taxane. TRIAL DESIGN: This is an open-label, non-randomized, multicenter phase IIA clinical trial. Patients will receive intravenously pembrolizumab (200 mg) followed by eribulin (1.23 mg/m2) on day 1 of each cycle (every three weeks). Eribulin will also be administered alone on day 8 of each cycle until progression or unacceptable toxicity. The end of study will be 12 months after last study dose or progressive disease experienced in all patients. The principal selection criteria are: (1) HR-positive/HER2-negative inoperable locally recurrent or MBC; (2) prior therapy with an anthracycline and a taxane in the early or metastatic disease setting unless contraindicated; (3) at least one, but not more than two, previous chemotherapeutic regimens for locally recurrent and/or MBC; (4) measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1; (5) available tumor tissue for PD-L1 biomarker analysis. The primary objective of the study is to assess the efficacy of this combination as determined by the clinical benefit rate (CBR) defined as the percentage of patients who achieve complete response, partial response, or stable disease ≥24 weeks based on RECIST v.1.1. Secondary objectives evaluate: (1) safety-related outcomes and (2) efficacy measures as progression-free survival (PFS), overall survival, overall response rate (ORR), and duration of response in the intention-to-treat population and in patients with PD-L1 positive tumors. Exploratory objectives include: (1) the analysis of PFS and ORR based on irRECIST; and (2) the identification of new predictive factors of response to the combination of pembrolizumab and eribulin based on gene signatures, mutational load, and circulating tumor cells. The trial uses an exact single-stage design. We hypothesized that excluding a CBR ≤30% while targeting an improvement of the CBR to ≥50% would be an optimal approach to evaluation of the study strategy. At least 17 patients with clinical benefit among 39 evaluable patients will be adequate to justify the investigation of this strategy in further clinical trials. Considering a drop-out rate of 10%, a sample size of 44 patients will be needed to attain 80% power at nominal level of one-sided alpha of 0.05. TRIAL REGISTRATION: NCT03222856. Date of registration: July 19th, 2017. First Patient First Visit: December 14th, 2017. Citation Format: José Manuel Pérez García, Antonio Llombart, José Luis Alonso, Begoña Bermejo, Lourdes Calvo, Vicente Carañana, Giuseppe Curigliano, Susana de la Cruz Sánchez, María Gión Cortés, Raúl Márquez Vázquez, Aleix Prat, Manuel Ruiz Borrego, Miguel Sampayo, Peter Schmid, Miguel Ángel Seguí, Javier Cortés, Esther Holgado. A phase II study of pembrolizumab and eribulin in patients with HR-positive/HER2-negative metastatic breast cancer previously treated with anthracyclines and taxanes (KELLY study) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT152.

Pembrolizumab in Combination with Lenalidomide and Low-Dose Dexamethasone for Relapsed/Refractory Multiple Myeloma (RRMM): Keynote-023

Pembrolizumab in Combination with Lenalidomide and Low-Dose Dexamethasone for Relapsed/Refractory Multiple Myeloma (RRMM): Keynote-023