Long-term follow up of patients with mesothelioma treated with dendritic cell therapy in three phase I trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2618-2618
Author(s):  
Daphne W Dumoulin ◽  
Robin Cornelissen ◽  
Koen Bezemer ◽  
Sara Baart ◽  
Joachim Aerts
Keyword(s):  
Phase I ◽  
Phase 1 ◽  
Phase I Trials ◽  
Tumor Lysate ◽  
Phase 1 Trials ◽  
Three Phase ◽  
Long Term Follow Up ◽  
Vaccination Therapy

2618 Background: Immunotherapy targeting PD-(L)1 has become indispensable in the treatment of many malignant tumors. Recently, checkpoint inhibition using anti-PD-1 in combination with anti-CTLA-4 was proved to be effective in patients with malignant pleural mesothelioma (MPM). However, the minority of patients benefit from this treatment. The lack of immunotherapy efficacy in the majority of patients with mesothelioma can be explained by the fact that mesothelioma is a tumor with an “immune-desert” phenotype, meaning a non-inflamed tumor characterized by low T-cell infiltration. By administration of dendritic cells (DCs), which were cultured, activated, and exposed to antigens ex-vivo, this “immune-desert” phenotype might be turned into an “inflamed” phenotype. Previously, we performed and published three phase I trials using activated DCs, which support this concept. Here, we report the long-term survival of the patients treated with DCs in these three phase 1 studies. Methods: We collected the survival data of the phase 1 trials using DC therapy in patients with MPM. In the first two trials, DCs loaded with autologous tumor lysate were used, while in the third allogeneic tumor lysate was used to load the DCs (Mesopher). Results: Between 2006 and 2015, in the three studies combined, 29 patients with MPM were treated with DC vaccination. At data cut-off, the median OS was 27 months (95% confidence interval (CI): 21 – 47 months). OS at 2 years was 55.2% (95% CI: 39.7%-76.6%), OS at 5 years was 20.7% (95% CI: 10.1%-42.2%). Conclusions: The long-term follow up of MPM patients treated with DC vaccination in the three separate phase 1 trials show a promising signal, with a 2-year OS of over 50% and a 5-year OS of over 20%. In addition, 2 patients are alive after 10 years of treatment. In our opinion, these findings show the potency of DC vaccination therapy in long-term activation of the immune system. DC vaccination therapy in patients with MPM is currently being investigated in a large, randomized phase II-III trial (NCT03610360) and in pancreatic cancer. Additional biomarker studies, as well as treatment combinations with for example ICI, could further improve the outcomes of DC-vaccination therapy. Clinical trial information: NCT02395679. [Table: see text]

scholarly journals OS09.6 Long-term follow-up data from 126 patients with recurrent high grade glioma from three Phase 1 trials of Toca 511 and Toca FC: Update and justification for a Phase 2/3 trial

2017 ◽  
Vol 19 (suppl_3) ◽  
pp. iii19-iii19
Author(s):  
M. Aghi ◽  
M. A. Vogelbaum ◽  
S. N. Kalkanis ◽  
D. Bota ◽  
D. Piccioni ◽  
...  
Keyword(s):  
Phase 1 ◽  
High Grade Glioma ◽  
High Grade ◽  
Phase 2 ◽  
Phase 1 Trials ◽  
Three Phase ◽  
Long Term Follow Up

Survival and long-term follow-up of the phase I trial of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in patients (pts) with previously treated advanced non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8030-8030 ◽  
Author(s):  
Julie R. Brahmer ◽  
Leora Horn ◽  
Scott J. Antonia ◽  
David R. Spigel ◽  
Leena Gandhi ◽  
...  
Keyword(s):  
Phase I ◽  
T Cell Activation ◽  
Cell Activation ◽  
Phase I Trial ◽  
Phase 1 ◽  
Prior Chemotherapy Regimen ◽  
Long Term Follow Up ◽  
Previously Treated

8030 Background: The immune checkpoint receptor programmed death-1 (PD-1) negatively regulates T-cell activation. Nivolumab, a PD-1 receptor blocking antibody, was evaluated in a phase 1 study in pts with various tumors including NSCLC (Topalian et al, NEJM 2012;366:2443). Methods: Pts with ≥1 prior chemotherapy regimen received nivolumab (1-10 mg/kg IV Q2W) for ≤12 cycles (4 doses/8W cycle) or until discontinuation criteria were met. We report initial overall survival (OS) and updated safety and response data for NSCLC pts. Results: 127 pts evaluable for safety received nivolumab at 1, 3, or 10 mg/kg as of July 2012. Common drug-related AEs were decreased appetite (9%), anemia (8%), diarrhea, nausea, and pruritus (7% each). The most common G3/4 AEs were fatigue, pneumonitis, and elevated AST (2% each). Two drug-related deaths from pneumonitis occurred early in the trial and led to increased monitoring without further deaths from pneumonitis. Median OS (mOS) across all dose cohorts was 9.2 mo and 9.6 mo for squamous (sq) and non-sq NSCLC, respectively. mOS was not reached at the 3 mg/kg dose (phase 3 dose) for either histology. Sustained OS was observed, with 44%/ 41% and 44%/ 17% of pts (sq/non-sq) alive at 1 and 2 years, respectively (Table). Prolonged ORs occurred in both histologies (Table). Conclusions: In this long-term follow-up of a phase I trial, nivolumab had an acceptable safety profile and showed an encouraging sustained OS benefit across histologies in previously treated advanced NSCLC. Follow-up through a Feb 2013 data cut (≥1 yr follow-up for all pts) will be provided at presentation. Clinical trial information: NCT00730639. [Table: see text]

scholarly journals Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up

Blood ◽  
2018 ◽  
Vol 131 (21) ◽  
pp. 2331-2334 ◽  
Author(s):  
Robert J. Kreitman ◽  
Martin S. Tallman ◽  
Tadeusz Robak ◽  
Steven Coutre ◽  
Wyndham H. Wilson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Aspirate ◽  
Phase 1 ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Key Points ◽  
Long Term Follow Up ◽  
Minimal Residual

Key Points Moxetumomab pasudotox eradicated HCL MRD in >50% of CRs, even by the most sensitive measure, bone marrow aspirate flow cytometry. Elimination of MRD was significantly associated with prolonged CR duration.

Long-term follow-up of a phase I study of high-dose decitabine, busulfan, and cyclophosphamide plus allogeneic transplantation for the treatment of patients with leukemias

Cancer ◽  
2003 ◽  
Vol 97 (5) ◽  
pp. 1242-1247 ◽  
Author(s):  
Marcos de Lima ◽  
Farhad Ravandi ◽  
Munir Shahjahan ◽  
Borje Andersson ◽  
Daniel Couriel ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Allogeneic Transplantation ◽  
High Dose ◽  
Long Term Follow Up

Long-term follow-up results of a phase I/II study of concurrent chemoradiotherapy for localized nasal NK/T-cell lymphoma (NKTCL): JCOG0211.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8050-8050
Author(s):  
Motoko Yamaguchi ◽  
Kensei Tobinai ◽  
Masahiko Oguchi ◽  
Naoki Ishizuka ◽  
Yukio Kobayashi ◽  
...  
Keyword(s):  
Phase I ◽  
Concurrent Chemoradiotherapy ◽  
Elevated Serum ◽  
Progression Free Survival ◽  
Disease Recurrence ◽  
Newly Diagnosed ◽  
Long Term Follow Up ◽  
Grade 3

8050 Background: Concurrent chemoradiotherapy has been regarded as one of the standard management for localized nasal NKTCL. However, its long-term efficacy and toxicity is not known. Methods: The JCOG0211 trial is a phase I/II study of concurrent chemoradiotherapy consisting of radiotherapy (RT) of 50 Gy and 3 cycles of DeVIC (carboplatin, etoposide, ifosfamide, dexamethasone) for newly diagnosed, localized nasal NKTCL (JCO 2009). Patients (Pts) with newly diagnosed, localized diseases (IE & contiguous IIE with cervical node involvement) who were 20-69 yrs of age with PS 0-2 were eligible. 3-D conformal RT planning with a wide margin (+ 2 cm to the gross tumor, the entire nasal cavity and the nasopharynx) and a 2-step cone down were required. 33 pts were enrolled in the study, 27 of whom were treated with RT and a 2/3-dose of DeVIC, which was selected as the recommended phase II dose in the preceding phase I portion of the trial. All pts completed RT without any protocol violations. Long-term follow-up results on overall survival (OS), progression-free survival (PFS) and toxicity were evaluated. Results: The median follow-up was 69 months (range, 62-96). The pt (N=33) characteristics were as follows: median age 54 yrs (range, 21-68); stage IIE 33%; B symptom (+) 36%; elevated serum LDH 21%. %5-yr OS and PFS were 73% (95%CI, 54-85%) and 67% (95%CI, 48-80%), respectively. 11 pts (33%) experienced disease recurrence. Two achieved a 2nd CR by salvage chemotherapies followed by allogeneic stem cell transplantation, and the remaining 9 pts died of disease. There was no observed death and disease progression after 34 and 31 months, respectively. One pt experienced Grade 3 irregular menstruation for 3 years. No other Grade 3 or 4 late non-RT-associated adverse events (AEs) were observed. One pt received plastic surgery due to Grade 4 RT dermatitis. No other Grade 3 or greater RT-associated late AEs were encountered. Conclusions: Both survival benefit and disease control from concurrent chemoradiotherapy with RT and DeVIC are maintained during a 5-yr follow-up, indicating the excellent efficacy of this approach as a first-line therapy for localized nasal NKTCL. Long-term toxicity is acceptable.

Clinical outcome and prognosis of metastatic colorectal cancer (mCRC) patients (pts) on phase 1 trials: A single institution experience from 1999 to 2016.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 828-828
Author(s):  
Audrey E. Kam ◽  
Gopichand Pendurti ◽  
Umang H. Shah ◽  
Mohammad Haroon Ghalib ◽  
Imran Chaudhary ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Phase I ◽  
Risk Score ◽  
Phase 1 ◽  
Median Number ◽  
Direct Bilirubin ◽  
P Value ◽  
Phase I Trials ◽  
Phase 1 Trials ◽  
Valuable Treatment

828 Background: Pts with mCRC who progress on all standard therapies have a poor prognosis and limited therapy options. Phase 1 trials represent a valuable treatment option. Herein we report the characteristics and outcomes of mCRC patients treated at our institution. Methods: We reviewed records of pts with mCRC enrolled on phase I trials at our institution from January 1999 to December 2016. Treatment-related response, toxicity, and deaths were recorded. Prognostic factors for overall survival (OS) were calculated using univariate (UVA) and multivariable Cox PH analysis (MVA). Results: We observed 187 enrollments with 152 unique patients accrued on 37 phase I trials. Median age was 59 years (range 29-83) and median number of prior therapies was 3 (range 0-8). 144 patients were evaluable for response. The clinical benefit rate (SD+response, CBR) was 33.2% and the ORR was 4.3%. Grade 3/4 non-hematological and hematological AE were seen in 25.5% and 17.3% of patients, respectively. Treatment-related mortality was 0.5%. Median PFS was 1.7 mos and OS was 8.2 mos. In UVA, the following variables predicted a shorter OS: age (p = 0.049); PS > 1 (p < 0.01); sites of metastases > 2 (p = 0.04); LDH > ULN (p < 0.001); albumin < 3.5 (p < 0.001); direct bilirubin > ULN (p = 0.02); WBC > 5.2 (p = 0.001); anemia (p = 0.046). In MVA, age > 60 (HR 1.63, p < 0.004), albumin < 3.5 (HR 3.69, p < 0.001), direct bilirubin > ULN (HR1.69, p < 0.01), and WBC > 5.2 (HR 1.97, p < 0.001) were negative prognostic factors for OS, adjusted for race and sex. A risk score based on MVA revealed that patients with a score of 0-1 had an improved OS (12.5mos) compared to a score of 2 (9.1mos, p-value < 0.005) and 3 (3.2 mos, p-value < 0.001). Conclusions: Patients with mCRC enrolled on phase 1 trials had a CBR of 33.2% and median OS of 8.2 mos, which exceeds third line therapies including regorafenib and trifluridine/tipiracil. Negative prognostic factors for OS were: age > 60, albumin < 3.5, direct bilirubin > ULN, and WBC > 5.2. A risk score based on these parameters showed that patients with a higher score had a significantly shorter OS, which may be useful in selecting patients for phase 1 trials.

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