A phase II trial of ZD 1869 for advanced cutaneous squamous cell carcinoma of the head and neck

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6038-6038
Author(s):  
R. S. Weber ◽  
R. Lustig ◽  
B. Glisson ◽  
D. Rosenthal ◽  
E. Kim ◽  
...  
Keyword(s):  
High Risk ◽  
Head And Neck ◽  
Stable Disease ◽  
Progressive Disease ◽  
Active Agent ◽  
High Risk Patient ◽  
Risk Of Death ◽  
Elevated Liver Enzymes ◽  
Number Of Patients ◽  
Definitive Therapy

6038 Background: Advanced HN CSSC carries a 30–40% risk of death by 2 years with standard therapies. A number of patients (pts) with clinically aggressive CSCC tend to have a poor prognosis when treated with standard approaches using surgery and radiation (RT), thus novel therapies are needed. CSSC over expresses the epidermal growth factor receptor (EGFR) and these compounds have activity in head and neck cancers. We are studying the use of gefitinib as an induction therapy in a high-risk patient group prior to definitive therapy to determine the overall efficacy, toxicity and feasibility. Methods: Eligible pts must have HN CSSC >2cm, regional nodal metastases, peri-neural invasion, or deep invasion into cartilage, muscle or bone and must be candidates for definitive local-regional therapy with surgery and/or radiation. Two 30-day cycles of gefitinib 250mg administered orally are given daily prior to definitive therapy. Pts are assessed clinically after the first 30-day cycle. If a response is noted, gefitinib is continued. For patients with stable disease, the dose is escalated to 500mg daily. Pts with progressive disease go off study. Biomarker evaluations including EGFR and Akt expression prior to and after induction are planned. Results: To date, 14 pts have been enrolled. 10 are evaluable for response and 13 for toxicity. A complete clinical response (CR) was noted in 3 pts (30%, one pathological CR), partial response in 2 patients (20%), stable disease in 2 (20%) and progressive disease in 3 (30%). Therapy was well tolerated with 2 patients having grade 3 toxicity (rash, diarrhea, or elevated liver enzymes). Conclusions: Standard definitive surgery and RT are inadequate for patients with advanced HN CSSC. The emergence of targeted therapies has given new hope for many patients with high-risk cancers. The preliminary results from our study suggest that gefitinib is an active agent for HN CSCC, and is well tolerated. Correlative studies may help identify patients most likely to respond to anti- EGFR therapy. [Table: see text]

Perioperative management of the high-risk surgical patient: cardiac surgery

2017 ◽  
Author(s):  
Marco Ranucci ◽  
Serenella Castelvecchio ◽  
Andrea Ballotta
Keyword(s):  
Cardiac Surgery ◽  
High Risk ◽  
Heart Surgery ◽  
Artery Bypass ◽  
Bypass Graft ◽  
High Risk Patient ◽  
Advanced Age ◽  
Bleeding Complications ◽  
Surgical Patient ◽  
Number Of Patients

During the last decade, as a result of continually improving surgical strategy and the technology which supports it (e.g. anaesthesia), cardiac surgery is offered to patients with advanced age and those with increasingly complex co-existing conditions that were previously considered to be contraindications. In addition, an increasing number of patients have previously undergone angioplasty, thereby delaying their initial coronary artery bypass graft surgery to a more advanced age. In general, candidates for cardiac surgery may now be not only older than in the past, but also more likely to have health problems such as hypertension and diabetes. Risk stratification may help to identify ‘the’ high-risk patient: ‘pre-warned is pre-armed’. In high-risk cardiac surgery patients, the surgical treatment options and perioperative care must be tailored to each patient, in order to optimize the benefits and minimize the risk of detrimental effects. The preoperative anticoagulation practice is an important aspect, balancing the risk between ischaemic and bleeding complications. New antiplatelet agents and oral anticoagulants have been recently delivered, and their role in patients scheduled for heart surgery is an additional important issue.

Phase II Trial of Intratumoral Administration of ONYX-015, a Replication-Selective Adenovirus, in Patients With Refractory Head and Neck Cancer

2001 ◽  
Vol 19 (2) ◽  
pp. 289-298 ◽  
Author(s):  
J. Nemunaitis ◽  
F. Khuri ◽  
I. Ganly ◽  
J. Arseneau ◽  
M. Posner ◽  
...  
Keyword(s):  
Head And Neck ◽  
Phase Ii ◽  
Stable Disease ◽  
Progressive Disease ◽  
Phase Ii Trial ◽  
Intratumoral Injection ◽  
Antitumoral Activity ◽  
Complete Regression ◽  
Standard Regimen ◽  
Disease Rates

PURPOSE: To determine the safety, humoral immune response replication, and activity of multiple intratumoral injections of ONYX-015 (replication selective adenovirus) in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN).PATIENTS AND METHODS: This phase II trial enrolled patients with SCCHN who had recurrence/relapse after prior conventional treatment. Patients received ONYX-015 at a dose of 2 × 1011particles via intratumoral injection for either 5 consecutive days (standard) or twice daily for 2 consecutive weeks (hyperfractionated) during a 21-day cycle. Patients were monitored for tumor response, toxicity, and antibody formation.RESULTS: Forty patients (30 standard and 10 hyperfractionated) received 533 injections of ONYX-015. Standard treatment resulted in 14% partial to complete regression, 41% stable disease, and 45% progressive disease rates. Hyperfractionated treatment resulted in 10% complete response, 62% stable disease, and 29% progressive disease rates. Treatment-related toxicity included mild to moderate fever (67% overall) and injection site pain (47% on the standard regimen, 80% on the hyperfractionated regimen). Detectable circulating ONYX-015 genome suggestive of intratumoral replication was identified in 41% of tested patients on days 5 and 6 of cycle 1; 9% of patients had evidence of viral replication 10 days after injection during cycle 1, and no patients had evidence of replication ≥ 22 days after injection.CONCLUSION: ONYX-015 can be safely administered via intratumoral injection to patients with recurrent/refractory SCCHN. ONYX-015 viremia is transient. Evidence of modest antitumoral activity is suggested.

Prior Treatment with Chemotherapy Is Associated with Poor Outcomes of High Risk Skin Cancers in Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3920-3920
Author(s):  
Matthew S. Davids ◽  
Nicole F. Velez ◽  
Pritesh Karia ◽  
Ye Guo ◽  
Alexander R. Vartanov ◽  
...  
Keyword(s):  
High Risk ◽  
Skin Cancer ◽  
Local Recurrence ◽  
General Population ◽  
Head And Neck ◽  
Lymphocytic Leukemia ◽  
Nodal Metastases ◽  
Cancer Outcomes ◽  
Risk Of Death ◽  
Skin Cancers

Abstract Abstract 3920 The increased incidence of skin cancer in patients with chronic lymphocytic leukemia (CLL) has been well-documented; however, the outcomes for CLL patients with high risk skin cancers are not as well-characterized. Moreover, little is known about the association between outcomes of high risk skin cancers and CLL prognostic factors or exposure to prior chemotherapy. We identified 225 patients at our institutions over the last 20 years with concurrent CLL and skin cancer, and we retrospectively examined outcomes for the 139/225 (61.8%) who had high risk skin cancer as defined by a diagnosis of squamous cell carcinoma (SCC), melanoma, or Merkel cell carcinoma (MCC). Poor skin cancer outcome (defined by local recurrence, nodal metastasis, and disease specific death) was determined by review of patient medical records and verified by pathology reports. Associations between various risk factors and poor skin cancer outcomes were evaluated via chi-square statistics (STATA 12.0 College Station, TX). The study group included a representative CLL population, with 98/139 (70%) males and a median age at diagnosis of 65 years (range 35–84), with a median follow-up of 120 months (range 2–410). Over the course of the study, 76 CLL patients remained alive (55%), 16 patients died due to CLL (12%), and 42 patients died from other causes (30%), including 18 (13%) from skin cancer. Median age at time of skin cancer diagnosis was 72 years (range 44–98), and median follow-up time after skin cancer diagnosis was 41 months (range 2–182). Skin cancer diagnoses included SCC in 122 patients (81%), melanoma in 22 patients (13%), and MCC in 8 patients (6%). Sixty-three (45%) patients had more than one skin cancer diagnosed. In the 122 patients with SCC, there were a total of 353 tumors, 297 of which occurred in males (84%). Half of the SCCs were in the head and neck (n=175, 49.6%). Fifty-four SCCs (15%) were greater than 2 cm in diameter. Rates of nodal metastases and death due to SCC were 12% and 6%, respectively. In the 22 patients with melanoma, 14 occurred in men (63.6%), with the largest number of tumors again located on the head and neck (n=8, 36.4%). Breslow thickness was greater than 1 mm in 12 patients (54.5%). Local recurrence and nodal metastases each occurred in 5 patients (22.7%). The five patients (22.7%) who died due to melanoma were the same patients with nodal metastases. In the 8 patients with MCC, 5 patients (62.5%) were male, and there was no location predominance. Five tumors (62.5%) were greater than 2 cm at time of diagnosis, local recurrence occurred in 1 patient (12.5%), and 5 patients (62.5%) had nodal metastases, with 4 of these 5 dying from MCC. Interestingly, prior treatment with any CLL chemotherapy was significantly associated with poorer skin cancer outcome, with increased rates of local recurrence, metastatic disease, or death due to skin cancer (p=0.001). We also explored whether high risk CLL prognostic factors were associated with poorer skin cancer outcomes. Eleven out of 18 patients tested (61%) had unmutated IGHV, 9/69 patients tested (13%) had del(17p) or del(11q) cytogenetics, and 71 patients did not have prognostic marker data available. In this limited prognostic marker data set, neither unmutated IGHV, poor risk cytogenetics, nor advanced Rai stage was associated with skin-cancer specific outcomes. Overall, the majority of the skin cancers in our cohort occurred in males, and the most common site of disease was the head and neck, highlighting an area in need of especially close surveillance. Relative to the historical experience of high-risk skin cancer patients in the general population, we found skin cancers in our CLL population to be more aggressive. For example, 2 of the skin-cancer related deaths were in CLL patients with stage I melanoma, which is unusual in the general population. Additionally, rates of nodal metastases and death in our SCC group were 12% and 6%, respectively, compared to rates of 4% and 2% in most studies of SCC in the general population. Strikingly, the risk of death from skin cancer was equivalent to the risk of death from CLL. The poor skin cancer outcomes in patients in our study were driven by the group who had received prior chemotherapy. Outcomes were not influenced by high risk CLL prognostic markers, although this latter analysis was limited by incomplete data. Disclosures: No relevant conflicts of interest to declare.

Real-Life Efficacy Of Azacitidine In Myelodysplastic Syndromes According To IPSS Cytogenetic Profile

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5229-5229
Author(s):  
Massimo Breccia ◽  
Maria Teresa Voso ◽  
Luca Maurillo ◽  
Pasquale Niscola ◽  
Luana Fianchi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
Acute Leukemia ◽  
Stable Disease ◽  
Who Classification ◽  
Conflicts Of Interest ◽  
Real Life ◽  
Risk Of Death ◽  
Cytogenetic Profile ◽  
Good Risk

Abstract In the AZA001 trial, azacitidine prolonged OS in all cytogenetic IPSS risk subgroups and in particular reduced 67% risk of death for all patients with -7/del(7q). Aim of our study was to assess azacitidine efficacy according to cytogenetic risk at baseline in a large group of intermediate/high-risk MDS patients treated outside clinical trials. One hundred and sixty-six patients represented the whole cohort of patients with primary or secondary MDS (CMML were excluded) diagnosed and treated with azacitidine in 6 different hematologic units. Patients were recruited consecutively, without any criteria of exclusion. All patients received azacitidine with a schedule of 5+2+2 or of 7 consecutive days every 28 days until progression or unacceptable toxicity. Clinical parameters (age, sex, WHO classification, IPSS) and baseline cytogenetic evaluation were retrospectively collected. Of 166 patients recruited, 103 were males and 63 females; median age was 69.5 years (range 49-89). A median of 8 cycles was performed (range 1-60). According to IPSS stratification there were 29 patients with intermediate-1 risk, 118 patients with intermediate-2 and 15 high–risk (7 patients not determined). According to WHO classification, 37 patients were diagnosed as having RAEB-1, 101 patients as RAEB-2, 28 patients as RCMD. According to IPSS cytogenetic risk stratification, 88 patients were in the good risk, 22 patients were in intermediate risk and 39 in the poor risk. The most frequent cytogenetic aberration, apart from normal karyotype, was -7 or del(7q). According to cytogenetic stratification, after a median of 4 cycles for the first evaluation, we revealed the following responses according to IWG criteria: of 88 patients classified as good risk, 68 were evaluable and overall 30% achieved a complete (CR), partial remission (PR) or hematological improvement (HI), 59% maintained a stable disease, 4% progressed to acute leukemia and 7% failed to achieve any response. Of 22 patients classified as intermediate cytogenetic risk, 19 patients were evaluable after 4 cycles: overall, 52.6% achieved a CR/PR and 42% maintained a stable disease, none experienced a progression and 5% failed to achieve any response. Of 39 patients stratified as high cytogenetic risk, 30 were evaluable: 36.6% achieved a CR/PR/HI, 36% maintained a stable disease, 20% progressed to acute leukemia and 7% failed to achieve any response. Our results, based on a retrospective evaluation in a large series of patients treated outside clinical trials, shown that azacitidine was clinically effective independently from cytogenetic profile, as proved in the AZA001 trial. Disclosures: No relevant conflicts of interest to declare.

PALB2 mutations in Brazilian patients from North-Northeast regions.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13670-e13670
Author(s):  
Thamara Ferreira ◽  
Thais Ferreira Bomfim-Palma ◽  
Isabelle Joyce de Lima Silva-Fernandes ◽  
Gabriela Espirito Santo Felix ◽  
Inacelli Queiroz De Souza Caires ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Male Breast Cancer ◽  
Clinical Management ◽  
Susceptibility Gene ◽  
High Risk Patient ◽  
Male Breast ◽  
The North ◽  
Number Of Patients ◽  
Increased Risk

e13670 Background: Loss-of-function mutations in PALB2 gene are associated with increased risk for breast cancer and possibly pancreatic, ovarian, male breast, prostate, colorectal as others cancers. In Brazil it has been estimated that up to 1,516 new cases of hereditary breast cancer for 2020 in the North and Northeast regions. Analysis of susceptibility gene mutations helps identify precisely the high-risk patient and their families, whom need specific and personalized clinical management as high-risk individuals. Methods: Twenty-six patients with pathogenic mutations in PALB2 gene identify by next-generation sequencing from states of Bahia (11), Ceará (9), Pernambuco (5) and Rondônia (1) in the North and Northeast regions were analyzed. Results: Most of the patients analyzed had only breast cancer (80%), including two cases of male breast cancer (9,5%); the others were isolated cases of endometrial cancer (4%), breast and pancreas cancers (4%), breast and lung cancers (4%), only ovarian cancer (4%) and ovarian and breast cancers (4%). Most cancers were stage II or III (65%). Family history of cancer was observed in 22/26 (84%); the most common tumors were breast, prostate, pancreas and thyroid. The founder mutations were more frequent in exons: 4 (58%) and 12 (15%). Eleven variants were found as follow: c.1240C > T (19%); c.3256delC (15%); c.1671_1674delTATT (11.5%); c.355delC (11.5%); NC_000016.9:g.(?_23632673)_(23652488_?)del (11,5%). The greatest variety of mutations was found in the state of Bahia, probably due to the greater number of patients included (42%). Conclusions: These data suggest that changes in clinical management of PALB2 patients are needed since the phenotype observed exhibited pattern of hereditary tumors, including male breast cancer. Besides that, PALB2 gene should be included in painel gene analysis in patients from the North and Northeast of Brazil because its high frequency of pathogenic variants.

Gefitinib for advanced cutaneous squamous cell carcinoma of head and neck: Phase II trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6054-6054 ◽  
Author(s):  
R. S. Weber ◽  
R. A. Lustig ◽  
A. K. El-Naggar ◽  
D. I. Rosenthal ◽  
E. S. Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Stable Disease ◽  
Progressive Disease ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Egfr Gene ◽  
Correlative Studies

6054 Background: Advanced head and neck cutaneous squamous cell carcinoma (HN cSCC) carries a 30–40% risk of death by 2 years with standard therapies. Small molecular inhibitors of the epidermal growth factor receptor (EGFR) may have an impact. We evaluated gefitinib as an induction therapy in a high-risk patient (pt) group prior to definitive therapy to determine efficacy, toxicity and feasibility. Correlative studies of EGFR expression, gene mutation, and ploidy may serve as predictors of response. Methods: Eligible pts must have HN cSCC >2cm, regional nodal metastases, peri-neural invasion, or deep invasion and must be candidates for definitive locoregional therapy with surgery and/or radiation. Two 30-day induction cycles of gefitinib (250mg po qd). Pts are assessed clinically after 15 days. If a response is noted, gefitinib is continued. For pts with stable disease, the dose is escalated to 500mg qd. Pts with progressive disease go off study. Total and phosphorylated (p) EGFR protein expression was analyzed by immunohistochemistry and gene copy number by fluorescent in-situ hybridization (FISH). Results: To date, 23 pts are enrolled and 22 are evaluable for responses and toxicities. Complete responses (CR) were noted in 3 pts, partial response (PR) 7, stable disease (SD) 5, and progressive disease (PD) 7 (68.1% response per RECIST criteria). Minimal side effects are associated with gefitinib (cutaneous and GI related). EGFR and p-EGFR protein overexpression were observed in 5 of 11 (45.5%) pts tested thus far. Eight of the pts were FISH negative with respect to EGFR gene expression: 7 had low trisomy and 1 had low polysomy. Two were FISH positive and expressed high polysomy. No gene amplification was detected. No statistically significant correlations between EGFR gene or protein expression and responses to administration of gefitinib were found at this point in the analysis. Protein and gene expression analyses are ongoing. Conclusions: The preliminary results from our study are encouraging and suggest that anti-EGFR therapy may have a role in the adjuvant treatment of HN cSCC. Correlative studies may help identify pts most likely to respond to anti-EGFR therapy. No significant financial relationships to disclose.

Ineffectiveness of Closed Suction Drainage Cultures in the Prediction of Bacteriologie Findings in Wound Infections in Patients Undergoing Contaminated Head and Neck Cancer Surgery

1985 ◽  
Vol 93 (6) ◽  
pp. 743-747 ◽  
Author(s):  
Gary D. Becker
Keyword(s):  
Head And Neck Cancer ◽  
High Risk ◽  
Wound Infection ◽  
Head And Neck ◽  
Neck Cancer ◽  
High Risk Patient ◽  
Cancer Surgery ◽  
Rational Approach ◽  
Wound Infections ◽  
Closed Suction Drainage

Despite the use of perioperative antibiotics, wound infection remains a major source of morbidity after contaminated head and neck cancer surgery. Accurate preoperative indentification of the patient likely to develop wound infection or prediction of the pathogenic organisms would allow a rational approach to antibiotic prophylaxis or initiation of therapy at the first sign of infection. This prospective study of patients undergoing contaminated head and neck cancer surgery evaluated cultures from hemovac lines in the prediction of the patient at high risk for wound infection and the bacteriologie findings in subsequent wound infections. Cultures were obtained from aspirates of the hemovac lines in 30 patients; 13% (four of 30 patients) developed a wound infection. Aerobic isolates were recovered in 100% (30 of 30 patients). Pathogens were isolated from 75% (three of four) and 73% (19 of 26) of patients with and without infection, respectively. Anaerobic bacteria were recovered in 8% (two of 26) of patients. There was a correlation between hemovac isolates and the patient's subsequent recovery from the wound infection in 50% (two of four) of the infected wounds. Cultures of hemovac lines in patients undergoing contaminated head and neck cancer surgery were not predictive of the high-risk patient or the bacteriologie findings in subsequent wound infections.

scholarly journals Clinical Implications of Human Papillomavirus in Head and Neck Cancers

2006 ◽  
Vol 24 (17) ◽  
pp. 2606-2611 ◽  
Author(s):  
Carole Fakhry ◽  
Maura L. Gillison
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Head And Neck ◽  
Sexual Behaviors ◽  
Hpv Infection ◽  
Genetic Alterations ◽  
Sufficient Evidence ◽  
Clinical Implications ◽  
Risk Of Death ◽  
Increased Risk

Human papillomavirus (HPV) is now recognized to play a role in the pathogenesis of a subset of head and neck squamous cell carcinomas (HNSCCs), particularly those that arise from the lingual and palatine tonsils within the oropharynx. High-risk HPV16 is identified in the overwhelming majority of HPV-positive tumors, which have molecular-genetic alterations indicative of viral oncogene function. Measures of HPV exposure, including sexual behaviors, seropositivity to HPV16, and oral, high-risk HPV infection, are associated with increased risk for oropharyngeal cancer. HPV infection may be altering the demographics of HNSCC patients, as these patients tend to be younger, nonsmokers, and nondrinkers. There is sufficient evidence to conclude that a diagnosis of HPV-positive HNSCC has significant prognostic implications; these patients have at least half the risk of death from HNSCC when compared with the HPV-negative patient. The HPV etiology of these tumors may have future clinical implications for the diagnosis, therapy, screening, and prevention of HNSCC.

scholarly journals 432 Nemvaleukin alfa, a novel engineered IL-2 cytokine, in combination with the anti-PD-1 antibody pembrolizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma (ION-01 study)

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A462-A462
Author(s):  
Brian Gastman ◽  
Mac Cheever ◽  
Steven Fling ◽  
Cesar Perez ◽  
Manish Patel ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Partial Response ◽  
Combination Therapy ◽  
Adverse Events ◽  
Head And Neck ◽  
Stable Disease ◽  
Progressive Disease ◽  
Antitumor Effects ◽  
Antitumor Response ◽  
Best Response

BackgroundNemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel engineered cytokine that selectively binds to the intermediate-affinity IL-2R to preferentially activate and expand anti-tumor CD8+ T and NK cells with minimal expansion of regulatory T cells (Treg), thereby leveraging antitumor effects of the IL-2 pathway while mitigating potential toxicity that limits use.1 Nemvaleukin single-agent activity has been demonstrated in checkpoint inhibitor-experienced patients, and deep and durable responses have been achieved in combination with pembrolizumab in multiple tumor types (eg, breast, head and neck, gastrointestinal, genitourinary, gynecological).2MethodsION-01 (NCT04144517) is a nonrandomized trial in adult patients with histologically/cytopathologically confirmed diagnosis of metastatic/recurrent head and neck squamous cell carcinoma. Eligible patients have progressive disease after ≥8 weeks on anti-PD-(L)1 therapy. The primary endpoint is the rate of new or improved antitumor response after the addition of nemvaleukin. Secondary objectives include characterization of the antitumor response and evaluation of safety and tolerability of the combination regimen. Patients receive intravenous nemvaleukin (3 μg/kg) once daily for the first 5 days and pembrolizumab (200 mg) on day 1 of each 21-day cycle. Tumor imaging and biopsies were performed at baseline and at pre-specified times. We present preliminary safety and antitumor activity (RECIST v1.1) data as of June 2021.ResultsFourteen patients with progressive disease received combination therapy with nemvaleukin and pembrolizumab; 8 had no prior response to pembrolizumab, 6 had previous best response of stable disease or partial response. Mean (± SD) age was 62 ± 12 years, 86% were male, and all were Caucasian. Prior anti-cancer therapy included radiotherapy (93%) and surgery (50%). ECOG performance status was 0 (14%) and 1 (86%) at baseline. Treatment-related adverse events of any grade in ≥30% of patients were chills (64.3%), pyrexia (57.1%), fatigue (42.9%), and nausea (35.7%). Five patients had stable disease as best response. One patient achieved a partial response (complete response in the target lesion) and remains on treatment (8+ cycles). Expansion of CD8+ T and NK cells with minimal Treg expansion was observed.ConclusionsNemvaleukin and pembrolizumab combination therapy was generally well tolerated; adverse events were consistent with those observed with intravenous nemvaleukin in ARTISTRY studies [2]. Peripheral immune cell expansion profiles are comparable to that observed with the same regimen in the ARTISTRY 1 phase 1 study. Emerging data from pretreatment and on-treatment paired biopsies will further characterize specific antitumor effects of nemvaleukin and pembrolizumab in this patient population.AcknowledgementsThe authors would like to thank all the patients who are participating in this study and their families. The study is sponsored by Alkermes, Inc. Medical writing and editorial support was provided by Parexel, and funded by Alkermes, Inc.Trial RegistrationClinicalTrials.gov NCT04144517ReferencesLopes JE, Fisher JL, Flick HL, et al. ALKS 4230: a novel engineered IL-2 fusion protein with an improved cellular selectivity profile for cancer immunotherapy. J Immunother Cancer 2020;8:e000673. doi: 10.1136/jitc-2020-000673.Boni V, Winer IS, Gilbert L, et al. ARTISTRY-1: Nemvaleukin alfa monotherapy and in combination with pembrolizumab in patients (pts) with advanced solid tumors. J Clin Oncol 2021;39(Suppl 15):abstr 2513.Ethics ApprovalThis study was approved by Quorum Review IRB (now Advarra IRB), approval number QR 33752.

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