S. Fu

Electrocardiograms (ECGs) in phase I anticancer drug development: the MD Anderson Cancer Center experience with 8518 ECGs

BACKGROUND Cardiac sequelae from oncologic drugs are important in early cancer drug development. Prolongation of the corrected QT interval (QTc) by noncardiac drugs is the most common cause of drug development delays, nonapprovals and postmarketing withdrawals by the US Food and Drug Administration. PATIENTS AND METHODS We analyzed 8518 electrocardiograms (ECGs) in 525 consecutive cancer patients enrolled in 22 industry-sponsored phase I clinical trials, starting 1 January 2006. RESULTS Seventy-four patients [14%, 95% confidence interval (CI) 11% to 17%] with normal QTc at baseline had QTc intervals above upper limit of normal after treatment initiation; 33 (6%, 95% CI 4% to 9%) had prolonged QTc intervals at baseline, and only one (3%, 95% CI 0% to 16%) worsened after dosing. Seven of 33 patients (21%, 95% CI 9% to 39%) with prolonged baseline QTc had normalization of QTc intervals after dosing. All QTc prolongations were clinically insignificant; study drugs were continued uneventfully. Two of 525 patients (0.4%, 95% CI 0% to 1%) experienced cardiac serious adverse events (myocardial infarction possibly related to drug and unstable atrial flutter related to metastatic disease). Both cardiac events were detected by clinical assessment, not surveillance ECGs. CONCLUSION Frequent ECG monitoring provided no clinically significant information in 525 patients in early phase trials.BACKGROUND Cardiac sequelae from oncologic drugs are important in early cancer drug development. Prolongation of the corrected QT interval (QTc) by noncardiac drugs is the most common cause of drug development delays, nonapprovals and postmarketing withdrawals by the US Food and Drug Administration. PATIENTS AND METHODS We analyzed 8518 electrocardiograms (ECGs) in 525 consecutive cancer patients enrolled in 22 industry-sponsored phase I clinical trials, starting 1 January 2006. RESULTS Seventy-four patients [14%, 95% confidence interval (CI) 11% to 17%] with normal QTc at baseline had QTc intervals above upper limit of normal after treatment initiation; 33 (6%, 95% CI 4% to 9%) had prolonged QTc intervals at baseline, and only one (3%, 95% CI 0% to 16%) worsened after dosing. Seven of 33 patients (21%, 95% CI 9% to 39%) with prolonged baseline QTc had normalization of QTc intervals after dosing. All QTc prolongations were clinically insignificant; study drugs were continued uneventfully. Two of 525 patients (0.4%, 95% CI 0% to 1%) experienced cardiac serious adverse events (myocardial infarction possibly related to drug and unstable atrial flutter related to metastatic disease). Both cardiac events were detected by clinical assessment, not surveillance ECGs. CONCLUSION Frequent ECG monitoring provided no clinically significant information in 525 patients in early phase trials.

Multiplex KRASG12/G13 mutation testing of unamplified cell-free DNA from the plasma of patients with advanced cancers using droplet digital polymerase chain reaction

Background Cell-free DNA (cfDNA) from plasma offers easily obtainable material for KRAS mutation analysis. Novel, multiplex, and accurate diagnostic systems using small amounts of DNA are needed to further the use of plasma cfDNA testing in personalized therapy. Patients and methods Samples of 16 ng of unamplified plasma cfDNA from 121 patients with diverse progressing advanced cancers were tested with a KRASG12/G13 multiplex assay to detect the seven most common mutations in the hotspot of exon 2 using droplet digital polymerase chain reaction (ddPCR). The results were retrospectively compared to mutation analysis of archival primary or metastatic tumor tissue obtained at different points of clinical care. Results Eighty-eight patients (73%) had KRASG12/G13 mutations in archival tumor specimens collected on average 18.5 months before plasma analysis, and 78 patients (64%) had KRASG12/G13 mutations in plasma cfDNA samples. The two methods had initial overall agreement in 103 (85%) patients (kappa, 0.66; ddPCR sensitivity, 84%; ddPCR specificity, 88%). Of the 18 discordant cases, 12 (67%) were resolved by increasing the amount of cfDNA, using mutation-specific probes, or re-testing the tumor tissue, yielding overall agreement in 115 patients (95%; kappa 0.87; ddPCR sensitivity, 96%; ddPCR specificity, 94%). The presence of ≥ 6.2% of KRASG12/G13 cfDNA in the wild-type background was associated with shorter survival (P = 0.001). Conclusion(s) Multiplex detection of KRASG12/G13 mutations in a small amount of unamplified plasma cfDNA using ddPCR has good sensitivity and specificity and good concordance with conventional clinical mutation testing of archival specimens. A higher percentage of mutant KRASG12/G13 in cfDNA corresponded with shorter survival.

Aberrations in the epidermal growth factor receptor gene in 958 patients with diverse advanced tumors: implications for therapy

BACKGROUND Epidermal growth factor receptor (EGFR) mutations are associated with the response to EGFR inhibitors in patients with non-small-cell lung cancer (NSCLC). We sought to investigate EGFR aberrations in patients with diverse advanced cancers. PATIENTS AND METHODS Patients referred to the phase I clinic were evaluated for the presence of EGFR mutations and response to therapy. RESULTS EGFR aberrations were detected in 34 of 958 patients (3.5%). Though EGFR mutations were most frequent in NSCLC (21 of 131, 16%), they were also present in a variety of other solid tumors (13 of 827 patients, 1.6%) including adrenocortical (1/10 patients), skin (1/24), breast (1/55), carcinoid (1/8), cholangiocarcinoma (1/20), head and neck (1/61), ovarian (1/84), parathyroid (1/1), salivary gland (1/20), renal (1/17), sarcoma (2/38), and thymic carcinomas (1/7). Of the 13 EGFR aberration-positive non-NSCLC patients (median number of prior systemic therapies = 3), 6 had treatment with an EGFR inhibitor. Two patients (diagnosis = parathyroid tumor and basal cell carcinoma) achieved stable disease (SD), lasting 6 and 7 months, respectively. CONCLUSION We found EGFR aberrations in 1.6% of a large group of patients with diverse tumors other than NSCLC, and treatment with an EGFR inhibitor could be associated with prolonged SD.

Risk of serious toxicity in 1181 patients treated in phase I clinical trials of predominantly targeted anticancer drugs: the M. D. Anderson Cancer Center experience

BACKGROUND This study assessed toxicity in advanced cancer patients treated in a phase I clinic that focuses on targeted agents. PATIENTS AND METHODS An analysis of database records of 1181 consecutive patients with advanced cancer who were treated in the phase I program starting 1 January 2006 was carried out. RESULTS All patients were treated on at least 1 of the 82 phase I clinical trials. Overall, 56 trials (68.3%) had only targeted agents, 13 (15.9%) only cytotoxics, and 13 (15.9%) targeted and cytotoxic agents. Rates of grade 3 and 4 toxicity that were at least possibly drug related were 7.1% and 3.2%, respectively, and 5 of the 1181 patients (0.4%) died from toxicity that was at least possibly drug related. The most common grade 3 or more toxic effects were neutropenia, thrombocytopenia, anemia, dehydration, infection, altered mental status, bleeding, vomiting, nausea, and diarrhea. Eastern Cooperative Oncology Group (ECOG) performance status greater than zero and use of a cytotoxic agent were selected as independent factors associated with serious toxicity. CONCLUSION Phase I trials of primarily targeted agents showed low rates of toxicity, with 10.3% of patients experiencing grade 3 or 4 toxicity and a 0.4% rate of death, at least possibly drug related.BACKGROUND This study assessed toxicity in advanced cancer patients treated in a phase I clinic that focuses on targeted agents. PATIENTS AND METHODS An analysis of database records of 1181 consecutive patients with advanced cancer who were treated in the phase I program starting 1 January 2006 was carried out. RESULTS All patients were treated on at least 1 of the 82 phase I clinical trials. Overall, 56 trials (68.3%) had only targeted agents, 13 (15.9%) only cytotoxics, and 13 (15.9%) targeted and cytotoxic agents. Rates of grade 3 and 4 toxicity that were at least possibly drug related were 7.1% and 3.2%, respectively, and 5 of the 1181 patients (0.4%) died from toxicity that was at least possibly drug related. The most common grade 3 or more toxic effects were neutropenia, thrombocytopenia, anemia, dehydration, infection, altered mental status, bleeding, vomiting, nausea, and diarrhea. Eastern Cooperative Oncology Group (ECOG) performance status greater than zero and use of a cytotoxic agent were selected as independent factors associated with serious toxicity. CONCLUSION Phase I trials of primarily targeted agents showed low rates of toxicity, with 10.3% of patients experiencing grade 3 or 4 toxicity and a 0.4% rate of death, at least possibly drug related.

Cytokines Produced by Dendritic Cells Administered Intratumorally Correlate with Clinical Outcome in Patients with Diverse Cancers

Purpose: Dendritic cells (DC) initiate adaptive immune responses through the uptake and presentation of antigenic material. In preclinical studies, intratumorally injected activated DCs (aDCs; DCVax-Direct) were superior to immature DCs in rejecting tumors from mice. Experimental Design: This single-arm, open-label phase I clinical trial evaluated the safety and efficacy of aDCs, administered intratumorally, in patients with solid tumors. Three dose levels (2 million, 6 million, and 15 million aDCs per injection) were tested using a standard 3 + 3 dose-escalation trial design. Feasibility, immunogenicity, changes to the tumor microenvironment after direct injection, and survival were evaluated. We also investigated cytokine production of aDCs prior to injection. Results: In total, 39 of the 40 enrolled patients were evaluable. The injections of aDCs were well tolerated with no dose-limiting toxicities. Increased lymphocyte infiltration was observed in 54% of assessed patients. Stable disease (SD; best response) at week 8 was associated with increased overall survival. Increased secretion of interleukin (IL)-8 and IL12p40 by aDCs was significantly associated with survival (P = 0.023 and 0.024, respectively). Increased TNFα levels correlated positively with SD at week 8 (P < 0.01). Conclusions: Intratumoral aDC injections were feasible and safe. Increased production of specific cytokines was correlated with SD and prolonged survival, demonstrating a link between the functional profile of aDCs prior to injection and patient outcomes. Clin Cancer Res; 24(16); 3845–56. ©2018 AACR.

Abstract 3146: Circulating tumor DNA assay performance for detection and monitoring of KRAS mutations in urine from patients with advanced cancers

Introduction: Non-invasive urinary ctDNA-based liquid biopsy approach can be used to detect and track cancer driver mutations for rapid diagnosis and disease monitoring. Using highly sensitivity ctDNA mutation detection platform, we examined the detection of KRAS G12/13 mutations in urine obtained from advanced cancer patients, assessed urine sample requirements, and compared the results with matched tumor tissue in patients with advanced cancers. Methods: 41 patients with advanced solid cancer with KRAS mutations on archival tumor from CLIA laboratory testing were prospectively enrolled with informed consent (colorectal cancer, n = 29; non-small cell lung cancer, n = 6; pancreatic cancer, n = 2; ovarian cancer, n = 2; other, n = 2). Urine was collected before and during experimental therapies. Urinary DNA was isolated using a method that enriches for highly fragmented, systemically derived cell-free DNA. KRAS G12/13 analysis was performed using mutation enrichment PCR coupled with next generation sequencing (MiSeq). Analytical sensitivity of the KRAS G12/13 assay is 0.006% mutant alleles in the background of 60 ng wild-type (wt) DNA and 0.002% mutant alleles in 360 ng wt DNA. Clinical data was collected retrospectively from the electronic medical record. Results: For 41 patients enrolled on a study, urine volumes in pretreatment samples ranged from 13 to 120 mL (median, 55 mL). Urinary DNA yields were 151 to 23059 ng (median, 1039 ng). Using tissue as the reference, the positive percent agreement (PPA) between urine and tumor KRAS G12/13 test results was 54% (22/41) for urine samples with all volumes (13-120 mL) and any DNA input amount (2-360 ng) and 92% (12/13) for urine samples with volumes ≥50 mL and DNA input amount ≥60 ng. For metastatic CRC patient cohort, the PPA between urine and tumor KRAS G12/13 test result was 60% (18/30) for urine samples with all volumes and any DNA input amount (20-120 mL, 2-360 ng) and 100% (10/10) for urine samples with volumes ≥50 mL and DNA input amount ≥60 ng. Feasibility of longitudinal monitoring KRAS G12/13 mutational burden in urine of patients treated with experimental therapies was demonstrated. Conclusion: KRAS G12/13 mutational status can be assess in urinary DNA with highest PPA amongst patients with urine volume ≥50 mL and DNA input amount ≥60 ng (92%). KRAS mutation detection from urine should be considered as a viable approach, particularly when tumor tissue is not available. Citation Format: Takeo Fujii, Cecile Rose T. Vibat, Daniel D. Karp, Sarina A. Piha-Paul, Vivek Subbiah, Apostolia M. Tsimberidou, Siquing Fu, David S. Hong, Helen J. Huang, Kiran Madwani, Debra L. Andrews, Saege Hancock, Aung Naing, Rajyalakshmi Luthra, Bryan K. Kee, Scott Kopetz, Mark G. Erlander, Vlada Melnikova, Funda Meric-Bernstam, Filip Janku. Circulating tumor DNA assay performance for detection and monitoring of KRAS mutations in urine from patients with advanced cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3146.

Abstract P4-13-11: Everolimus, letrozole and trastuzumab in estrogen receptor and HER2-positive patients with metastatic breast cancer and other solid tumors: Evaluating synergy and overcoming resistance

Background Combining anti-estrogen therapy with HER2 and mTOR inhibitors may be synergistic and overcome resistance to hormonal and anti-HER2 therapies in patients with estrogen receptor (ER)-positive and HER2 receptor amplified and/or mutant advanced cancers. Patients and Methods We evaluated the mTOR inhibitor everolimus, aromatase inhibitor letrozole and anti-HER2 antibody trastuzumab in patients with ER-positive, HER2-positive and/or mutant, solid tumors (confirmed by IHC, FISH, and/or HER2 sequencing). The primary objectives were to determine maximum tolerated dose (MTD) and toxicity and to evaluate response. Secondary objectives were to correlate activity with genomic and proteomic signatures. Next-generation sequencing (NGS) was performed either using a 50-gene panel or externally by Foundation Medicine (Cambridge, MA, USA). Results Nine of 10 patients enrolled are currently evaluable for toxicity and response including 7 patients with breast cancer, one patient with ovarian cancer, and one patient with cervical cancer. The median age was 57 years (range, 33-66 years) and the median number of prior therapies in the metastatic setting was 5 (range, 2-7). Of these nine patients, six were HER2+ (by IHC and/or FISH) and three had HER2 mutations (in the absence of HER2 overexpression or amplification). Dose Level (DL) 1 consisted of trastuzumab loading dose of 4mg/kg IV and maintenance dose of 2 mg/kg IV every 21 days, everolimus 5 mg PO daily and letrozole 2.5 mg PO daily. DL2 consisted of trastuzumab loading dose of 6mg/kg IV and maintenance dose of 4 mg/kg IV every 21 days, everolimus 5 mg PO daily and letrozole 2.5 mg PO daily. DL3 consists of trastuzumab loading dose of 6 mg/kg IV and maintenance dose of 4 mg/kg IV every 21 days, everolimus 7.5 mg PO daily and letrozole 2.5 mg PO daily. Currently patients are being enrolled in DL3 and no DLTs have been observed. Additional dose levels are planned with increased trastuzumab and everolimus to the FDA approved doses or until MTD is reached. The most common grade 1 and 2 treatment-related toxicities were fatigue (6 patients), anemia and constipation (2 patients each). No grade 3 or 4 toxicities have been reported. Median time to treatment failure (TTF) was 7.4 months (95% CI 5.2-9.6). One patient with breast cancer and a HER2 mutation experienced a partial response (PR) with a 32% decrease in measurable disease. This patient had no prior HER2-targeted therapy and previously progressed while on letrozole and while on exemestane and everolimus. Six additional patients experienced stable disease (SD) ≥ 6 months, 5 with breast cancer and 1 with cervical cancer. Of these 6 patients, 1 had a HER2 mutation and another had a PIK3CA mutation. Conclusions Combination treatment with everolimus, letrozole and trastuzumab is well tolerated and active in ER+, HER2+ and/or mutant solid tumors, including breast and cervical cancer. Clinical benefit (PR/SD≥6 months) was seen in 7 of 9 patients (78%), including patients with HER2 mutations in the absence of overexpression and/or amplification and patients with no genomic alterations in the PI3K/AKT/mTOR pathway. Enrollment is ongoing. Citation Format: Janku F, Hong DS, Atkins JT, Karp DD, Tsimberidou AM, Piha-Paul SA, Subbiah V, Naing A, Fu S, Moulder SL, Tripathy D, Meric-Bernstam F, Wheler JJ. Everolimus, letrozole and trastuzumab in estrogen receptor and HER2-positive patients with metastatic breast cancer and other solid tumors: Evaluating synergy and overcoming resistance. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-11.

Abstract LB-C17: A phase I study of everolimus (mTOR inhibitor) in combination with vandetanib (multikinase inhibitor of VEGFR, EGFR, and RET) in advanced solid tumors including molecularly matched aberrations

Background:RET gene aberrations including fusions have been identified across several types of solid malignancies, including lung adenocarcinomas, thyroid, colorectal and invasive breast cancers. Preclinical models has shown that the combination of vandetanib (VAN), a multi tyrosine kinase inhibitor of VEGFR2/EGFR and RET pathways) and everolimus (EV), an mTOR pathway inhibitor, overcomes intrinsic and /or acquired tumor resistance to either agent alone, suggesting a rationale for investigating this combination in cancer patients, including those harboring aberrations in the drug targets. Methods: We designed a dose escalation and expansion trial with “3+3” design to determine the safety, maximum tolerated dose (MTD), recommended Phase II dose (RP2D), dose-limiting toxicities (DLTs) and activity of the combination. During the escalation phase, the study drugs (VAN, EV) were given at the following doses, respectively: level 0 (100 mg, 2.5 mg), level 1 (200mg, 2.5mg), level 2 (200mg, 5mg), level 3 (300 mg, 5mg), and level 4 (300mg, 10mg). Both study drugs are given continuously on a 28 day schedule. Tumor responses are assessed using RECIST v1.1. Tumor molecular aberrations were detected by Next Generation Sequencing (NSG) and/or Fluorescence In Situ Hybridization (FISH). Results: To date, 72 adult patients have been treated. Median age was 56 years (range 18-82 years) and 38 patients (53%) were male. The most common diagnoses were sarcoma (n = 15); renal cell carcinoma (n = 11); thyroid cancer (n = 10; n = 3 medullary) lung cancer (n = 10). Thirty patients (41%) had 3 or more sites of metastases. Nine patients were treated at dose level 0 (VAN 100 mg daily + EV 2.5 mg daily), five at dose level 1 (VAN 200 mg daily + EV 2.5 mg daily), and 6 patients at dose level 4 (highest dose VAN 300 mg daily + EV 10 mg daily). The most common adverse events observed in patients across different dose levels included G1 rash (n = 10), G1-G3 diarrhea (n = 21); G1-G4 thrombocytopenia (n = 9); G1-G2 hypertriglyceridemia/hypercholesterolemia (n = 8); G1-G2 hypertension (n = 6), G1-G2 QTc prolongation (n = 4); G1-G transaminitis (n = 4). Dose escalation has been completed and the expansion phase is currently ongoing in patients with advanced malignancies harboring RET, or P13K, PIK3R1, TSC1/2 and AKT genomic aberrations. The best responses were PR (n = 7), and SD (n = 33). Ten patients with reported SD (30.3%) experienced durable responses (> 6 months). One RET M918T mutant medullary thyroid cancer patient, who developed acquired resistance to VAN, achieved a 25% reduction on this combination. Three NSCLC patients with RET fusions (100%) responded with one reaching 48% decrease per RECIST. In addition there was evidence of blood-brain barrier penetration in 2 patients with RET fusion patients who had brain metastases. Conclusions: The combination of VAN and EV was reasonably well tolerated at the highest doses of each of the drugs. Evidence of response was noted in heavily pre-treated patients with refractory solid tumors and targetable genomic aberrations specifically RET. The combination has CNS penetration in RET fusion NSCLC. Citation Format: Tina Cascone, Kenneth R. Hess, Sarina Piha-Paul, David S. Hong, Michael Roxas, Ishwaria M. Subbiah, Siquing Fu, Aung Naing, Filip Janku, Daniel Karp, Steven I. Sherman, Funda Meric-Bernstam, John V. Heymach, Vivek Subbiah. A phase I study of everolimus (mTOR inhibitor) in combination with vandetanib (multikinase inhibitor of VEGFR, EGFR, and RET) in advanced solid tumors including molecularly matched aberrations. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-C17.

Abstract C50: Phase I dose escalation study of the oral multi-kinase VEGF inhibitor regorafenib and the anti-EGFR monoclonal antibody cetuximab in patients with advanced solid tumors including colorectal cancer

Background: The combination of multi-kinase VEGF inhibitor regorafenib and anti-EGFR monoclonal antibody cetuximab overcame intrinsic and acquired resistance in both EGFR-sensitive and EGFR-resistant preclinical models of colorectal cancer (CRC). (Clin Cancer Res; 21(13); 2975-83) Methods: We designed a phase I study to determine the safety, maximum tolerated dose (MTD), recommended phase II dose (RP2D), and dose-limiting toxicities (DLTs) of the oral multi-kinase inhibitor regorafenib and the anti-EGFR monoclonal antibody cetuximab in patients (pts) with advanced cancer including metastatic colorectal cancer. Tumor responses were assessed using RECIST v1.1. Results: Twenty seven pts were enrolled between May 2014 and August 2015. 22 (81%) pts were evaluable for toxicity and response. 5 heavily pre-treated pts were not evaluable for DLTs because they discontinued the trial before the end of the DLT window, mainly because of disease progression. 21 pts were treated at dose level 1 (cetuximab IV 200 mg/m2 followed by 150 mg/m2 weekly + regorafenib 80 mg daily) and 6 pts at dose level 2. MTD was exceeded at dose level 2 (cetuximab IV 200 mg/m2 followed by 150 mg/m2 weekly + regorafenib 120 mg daily), with 2 DLTs observed, including G3 thrombocytopenia (n = 1) and G3 thrombocytopenia with intraperitoneal bleeding (n = 1). The most common adverse events observed in all patients across both dose levels tested included G1-2 rash, G1-2 hypomagnesaemia, G1 myalgia, G1 fatigue, G1 nausea/vomiting. In addition other AE9s included G2 hand-foot syndrome (n = 5), and G2 hypertension (N = 2). One patient with KRAS wt CRC achieved a partial response (PR) (46% decrease) lasting 15 months who was previously resistant to cetuximab. Another KRAS wt CRC patient with a hyper-mutated genotype [Lynch syndrome (MSI High), both BRCA1 and 2 mutations, FGFR3 mutation] achieved stable disease (SD) for > 10 months. 10 patients (37%) achieved SD>4 months or PR that included renal cell carcinoma (n = 1), EGFR mutant glioblastoma multiforme (n = 1), squamous cell cancer (n = 1) and carcinoma of unknown primary (n = 1). Conclusions: The combination of cetuximab and regorafenib was well tolerated at doses of cetuximab IV 200 mg/m2 followed by 150 mg/m2 weekly, with regorafenib 80 mg daily. Anticancer activity was observed in patients with wild type colorectal cancer. Citation Format: Vivek Subbiah, David S. Hong, Behrang Amini, Sarina Piha-Paul, Joanna Grace Fernandez, Siquing Fu, Apostolia M. Tsimberidou, Aung Naing, Filip Janku, Daniel D. Karp, Michael Overman, Cathy Eng, Scott Kopetz, Funda Meric-Bernstam, Gerald S. Falchook. Phase I dose escalation study of the oral multi-kinase VEGF inhibitor regorafenib and the anti-EGFR monoclonal antibody cetuximab in patients with advanced solid tumors including colorectal cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C50.

Safety, feasibility and functionality of activated autologous dendritic cells for intratumoral injection in solid tumors: a Phase I clinical trial

Meeting abstracts Dendritic cells (DC) are proficient in initiating adaptive immune responses, through the uptake and subsequent presentation to the immune system of antigenic compounds. In preclinical studies, activated DC (aDC; DCVax®-Direct) were shown to be superior to immature DC in clearing