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  • 1
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    The IMMULAB trial: A phase II trial of immunotherapy with pembrolizumab in combination with local ablation for patients with early stage hepatocellular carcinoma (HCC).
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. TPS4159-TPS4159
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. TPS4159-TPS4159
    Abstract: TPS4159 Background: The investigator-initiated IMMULAB study investigates the clinical activity of peri-interventional treatment with the anti-PD1 antibody pembrolizumab in HCC patients who are candidates for local ablation via either radiofrequency ablation (RFA), microwave ablation (MWA) or brachytherapy, or - as recommended for tumor larger than 3 cm – by combination with TACE. Patients with extrahepatic disease are excluded. Local ablation is known to induce tumor destruction with subsequent antigen release resulting in host adaptive immune responses. However, tumors could quickly overcome the immune responses by upregulating PD-L1/PD-1 expression and inhibiting the function of CD8 + and CD4 + T cells. Thus, combination of local ablation with an anti-PD1 antibody might display interesting effects by activating immune cells and disabling immune inhibitory mechanisms at the same time. Methods: This is a prospective investigator initiated single-arm multicenter phase II trial investigating immunotherapy with the PD-1 inhibitor pembrolizumab in combination with local ablation in early stage hepatocellular carcinoma (HCC). Patients with a child-pugh classification score ≤ 6, including high risk candidates for local ablation (defined as patients having ≤ 5 tumor nodules with diameters ≤ 7cm [longest axis] each OR patients with vascular infiltration) receive 200mg pembrolizumab i.v. q3w for 2 cycles. Thereafter, radiologic imaging is followed by local ablation on day 1 of cycle 3. Further pembrolizumab (200mg) is applied 2 days after ablation and thereafter every 3 weeks (q3w) for a total treatment duration of up to 12 months. It is planned to enroll 30 pts. Primary efficacy endpoint is the overall response rate (RECIST 1.1) after 2 cycles of pembrolizumab and before performing local ablation aiming in the conversion / downstaging of borderline candidates by pre-interventional treatment with pembrolizumab. Overall recruitment has started; currently (Feb 2021) 18 of 30 planned patients have been enrolled. Clinical trial information: NCT03753659.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.TPS4159
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 2
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    IMMUNIB trial (AIO-HEP-0218/ass): A single-arm, phase II study evaluating safety and efficacy of immunotherapy nivolumab in combination with lenvatinib in advanced-stage hepatocellular carcinoma (HCC).
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 4107-4107
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 4107-4107
    Abstract: 4107 Background: The field of systemic options in HCC therapy has significantly evolved in recent years, and first line options now include sorafenib, lenvatinib and bevacizumab plus atezolizumab. Nivolumab is a recombinant human IgG4 mAb targeting PD-1 with clinically meaningful activity in about 15-20% of HCC patients, but the confirmatory phase III trial Checkmate 459 failed to demonstrate superiority over sorafenib. VEGF signaling is not only a driver of tumor angiogenesis, but also contributes to the formation of an immunosuppressive microenvironment. Combinations of anti-angiogenic multikinase inhibitors, specifically lenvatinib, and PD-1/PD-L1 inhibitors have demonstrated remarkable antitumor activity and manageable toxicity in several tumor types, including HCC. We therefore aimed to evaluate the efficacy of nivolumab in combination with lenvatinib as first line treatment in patients with advanced HCC. Methods: This investigator-initiated single-armed phase II trial (NCT03841201) recruited 50 patients (pts) at 8 sites in Germany between 07/2019 and 05/2021. Primary endpoints were objective response rate (ORR) according to investigator assessed RECIST 1.1 and safety/tolerability. Secondary endpoints included ORR according to iRECIST, time to progression (TTP), progression free survival (PFS) and overall survival (OS). Recruitment of the trial was completed in 05/2021. At the time of analysis, 4 patients remained on treatment. Results: 50 pts (24 BCLC B, 24 BCLC C, 2 not evaluable) were enrolled and received at least one dose of the combination treatment. ORR by RECIST 1.1 was 28% (CR: 6.0%, PR: 22.0%, SD: 46.0%, PD: 12.0%). Median PFS was 9.0 mo (26 events). Median TTP was 11.5 mo (0.69 at 6 mo, 0.45 at 12 mo, 0.36 at 18 mo) and median OS was 27.1 mo (8 events). 45 (91.8%) pts experienced at least one TRAE, of which 29 pts (59.1%) encountered at least one TRAE ≥ grade 3. 17 (34.7%) pts had one or more SAE related to the study medication, whereof 15 pts (30.6%) experienced at least one treatment related SAE ≥ grade 3. Conclusions: No new safety signals were observed for the combination of nivolumab and lenvatinib. Although the study failed to reach its prespecified ORR of at least 40%, the high activity in all efficacy endpoints with a mOS of 27.1 mo supports the further investigation of the combination in HCC. Clinical trial information: NCT03841201.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.4107
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Efficacy and safety of nivolumab and trabectedin in pretreated patients with advanced soft tissue sarcomas (STS): Results of a phase II trial of the German Interdisciplinary Sarcoma Group (GISG-15, NitraSarc).
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 11500-11500
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 11500-11500
    Abstract: 11500 Background: Programmed death-1 (PD-1) inhibitors alone have modest activity in the treatment of most STS. A possible synergistic effect of combined trabectedin with PD-1 inhibitor nivolumab has been previously reported. Herein we evaluated the efficacy and safety of trabectedin plus nivolumab as a second-line treatment of patients with anthracycline-pretreated metastatic or inoperable STS. Methods: The prospective, explorative, two-group, non-randomized phase II NiTraSarc trial enrolled patients with advanced lipo- or leiomyosarcomas (Group A; GA) or with non-L-sarcomas (Group B; GB). Patients were initially treated with 3 cycles of trabectedin 1.5 mg/m 2 , followed by the combination of trabectedin 1.5 mg/m 2 plus nivolumab 240 mg in a so-called “late combination cohort” (LCC) for up to 16 cycles. After positive results of a preplanned interim analysis, patients received the combination therapy already starting from Cycle 2 in an “early combination cohort” (ECC). Primary efficacy endpoint was progression-free survival rate after 6 months (PFSR6) according to RECIST v.1.1. A central pathological assessment (CPA) was done from tumor specimen from all patients. Updated results according to cpa are presented. Results: A total of 92 patients were recruited in the trial: 43 patients in GA and 49 in GB. In GA, 28 patients (63%) had leiomyosarcoma and 15 (37%) had liposarcoma. Most common sarcoma types in GB were pleomorphic (n = 12), spindle cell (n = 11), fibromyxoid (n = 6), synovial (n = 5) and epithelial (n = 4) sarcoma. After median follow up of 16.6 months, overall PFSR6 as per CPA in GA was 47.6% (60% in LCC vs 36.4% in ECC) and 14.6% in GB. Median PFS was numerically higher in GA compared to GB (5.5 vs 2.3 months) and even longer in LCC vs ECC (9.8 vs 4.4 months). Median overall survival was more than three times longer in GA vs GB (18.7 vs 5.6 months) and, again, longer in LCC vs ECC (24.6 vs 13.9 months). Safety trabectedin and nivolumab was consistent with the safety profiles of each drug alone with no relevant new findings for the combination or between LCC and ECC. Conclusions: Our study confirms the activity of trabectedin plus nivolumab, particularly in patients with lipo- or leiomyosarcomas. There is a significant difference between ECC and LCC in terms of PFSR6, PFS and OS. The results in patients with non-L-sarcomas do not justify further investigation of this combination. Clinical trial information: NCT03590210 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.11500
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Efficacy and safety of nivolumab and trabectedin in pretreated patients with advanced soft tissue sarcomas (STS): Preliminary results of a phase II trial of the German Interdisciplinary Sarcoma Group (GISG-15, NitraSarc) for the non-L sarcoma cohort.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 11545-11545
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 11545-11545
    Abstract: 11545 Background: Single-agent PD-1 inhibitors have modest activity in the treatment of most STS. Potential strategies to increase efficacy include combination therapies targeting the tumor microenvironment. Considering that apart from direct growth inhibition and death of malignant cells, trabectedin (Tr) also induces macrophage depletion and/or different immunologic effects, suggesting a possible synergistic effect of combined Tr plus anti-PD-1 treatment. We therefore aimed to evaluate the efficacy and safety of combined Tr and nivolumab (Ni) as a second-line treatment in STS. Methods: The prospective, explorative, two group, non-randomized phase II NiTraSarc trial enrolled pretreated patients (pt) with advanced STS (Group A: lipo- or leiomyosarcomas, Group B: non-L-sarcomas). Pt were initially treated with 3 cycles of Tr 1.5 mg/m 2 , followed by the combination of Tr 1.5 mg/m 2 + Ni 240 mg (“late combination cohort” (LCC)) for up to 16 cycles. After positive results of a preplanned interim analysis, pt received the combination therapy starting with cycle 2 (“early combination cohort” (ECC)). 92 pt were recruited to the trial (55 in Group A, 37 in Group B). Primary efficacy endpoint is progression-free survival rate after 6 months (PFSR6) according to RECIST v.1.1. This is a first analysis of the primary efficacy endpoint in Group B based on a modified intention-to-treat (mITT) population of evaluable 36 pt: 23 and 13 pt from the LCC and ECC, respectively. Results: The most common Group B subtypes comprised undifferentiated pleomorphic/not otherwise specified sarcoma (UPS/NOS, 13pt) and fibromyxoid sarcoma (FMS, 6pt). After a median follow-up of 5 months (m) PFSR6 was 13.9% for all pt, 8.7% in LCC and 23.1% in ECC. Median duration of disease stabilization (DoDS) was 4m in all pt, the LCC and the ECC. Two pt had a partial response (PR), 10 had disease stabilization (SD), while 13 pt progressed, and 11 had missing data. By subtype: PR- UPS/NOS=2 (DoDS 12.7m/12.5m). SD: UPS/NOS=3, epithelioid=2, synovial=2, FMS=1, fibrosarcoma=1, other=1. All 36 pt experienced at least one adverse event (AE) reaching a total of 579 AEs, 141 (24.4%) of which were considered to be grade ≥3 treatment-related AEs. The main grade ≥3 AEs were: leukopenia (47.2% of pt), neutropenia (41.7% of pt), thrombocytopenia (33.3% of pt), increased ALT (30.6% of pt), and anemia (27.8% of pt). Conclusions: Tr+Ni was well tolerated and showed activity in at least some patients with non-L-sarcomas (mostly UPS/NOS) especially in the ECC. Analyses of the collected data, including PD-L1 expression profile, with the goal to establish whether Tr+Ni should be further pursued in these patients, are ongoing. ClinicalTrials.gov Identifier: NCT03590210; EudraCT: 2017-001083-38. Clinical trial information: NCT03590210.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.11545
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Open-label, randomized, multicenter, phase IV trial comparing parenteral nutrition using multi-chamber bags (Eurotubes) versus traditional 2/3-chamber bags in subjects with metastatic or locally advanced inoperable cancer requiring parenteral nutrition: The PEKANNUSS trial of the AIO.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. TPS7086-TPS7086
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. TPS7086-TPS7086
    Abstract: TPS7086 Background: Approximately 50% of all cancer subjects suffer from cancer anorexia-cachexia syndrome accompanied by an inadequate food intake and predicting mortality, poor therapeutic response, diminished functional capacity, and reduced QoL. Especially in the advanced stages, parenteral nutrition (PN) is often required and accompanied by an increased risk of blood stream infections associated with increased mortality and other serious medical conditions such as sepsis. Furthermore, the switch from oral food intake to PN changes the patient’s everyday life leading to reduced autonomy and flexibility (e.g. due to dependency on home nursing services). This study aims at evaluating the incidence of catheter-related infections (CRI) and the frequency of self-administered parenteral nutrition at home (HPN) in patients receiving standard PN via A) traditional two- or three-chamber bags (often requiring addition of vitamins and/or medications by home care service) or B). the multi-chamber bags Eurotubes (minimizing additional supplements and enabling self-administration by patients at home). In addition, one group of patients will receive low glucose HPN via Eurotubes to investigate a possible benefit on clinical outcome. Methods: This is an open-label, randomized, multicenter, investigator-initiated, phase IV trial. Overall, 350 patients with inoperable metastatic or locally advanced solid tumors who have an indication for parenteral nutrition will be enrolled. Patients will be randomized 1:1:1 ratio to Arm A (Standard PN using Eurotubes) or Arm B (Standard PN using 2/3-chamber bags), or to Arm A-1 (low glucose using Eurotubes). Patients will be assessed (physical exam, ECOG, weight, QoL, lab tests, AEs, HPN documentation) every 4 weeks during the 12 months HPN treatment period. Co-primary endpoints are incidence of CRI and patient autonomy (rate of self-administered PN at home). Secondary endpoints comprise weight change, change in albumin and CRP levels, overall survival, QoL, and safety. Recruitment has just started; first patient in was on February 5th, 2020. Clinical trial information: NCT04105777 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.TPS7086
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Open-label, phase I study evaluating feasibility and safety of subcutaneous IMP321 (LAG-3Ig fusion protein, eftilagimod alpha) combined with avelumab in advanced stage solid tumor entities: Results from stratum D of the INSIGHT platform trial.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 3099-3099
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 3099-3099
    Abstract: 3099 Background: Stratum D of the INSIGHT study investigates the feasibility and safety of s.c. application of IMP321 (eftilagimod alpha) combined with the PD-L1 inhibitor avelumab in advanced stage solid tumors. The MHC class II agonist IMP321 activates antigen-presenting cells followed by CD8 T-cell activation. The addition of avelumab aims at enhancing activity by combining IMP321’s activating effects on immune cells with the release of immune inhibitory effects caused by interruption of the PD-1/PD-L1 axis. Methods: This investigator-initiated phase I trial consists of four strata: intratumoral (A) or intraperitoneal IMP321 (B); s.c. IMP321 with SOC (C) or with PD-L1 inhibition (D). This abstract focuses on Stratum D. Patients (pts) receive 800mg avelumab i.v. q2w along with s.c. IMP321 injections (6mg IMP321 in cohort 1 and 30mg IMP321 in cohort 2). 12 pts are planned in stratum D : 6 pts in cohort 1 and 6 pts in cohort 2. Primary endpoint is safety. Results: So far, 8 pts have been enrolled (6 in cohort 1 and 2 in cohort 2). In 6 pts (cohort 1) treated for different tumor indications (gastric, gallbladder, colon cancer, pleural mesothelioma), no dose limiting toxicities occurred. 3 serious adverse events (SAEs) (1 acute kidney injury grade 5 in 1 pt, 2 preileus grade 3 in 1 pt) were reported, none of them was related to any of the study drugs. In total, 34 adverse events (AEs; grade 1-2, 21; grade 3, 12; no grade 4; grade 5, 1) have been documented in 5 pts. Most common grade 1-2 AEs were pain, nausea, and injection site reaction in 50%, 33%, and 17% of the pts. Most common grade 3 AEs were nausea/vomiting, preileus/ileus, and ascites in 33%, 33%, and 17% of the pts. One AE grade 5 (acute kidney injury) was reported. 4 AEs grade 1-2 were possibly or definitely related to IMP321 (injection site reaction 2x; fever; lipohypertrophy), 6 AEs grade 1-2 were possibly or definitely related to avelumab (nausea 2x; chills; fever; dyspnea; lipohypertrophy). All AEs grade 3-5 were unrelated to any of the study drugs. Of the 8 pts enrolled so far, 4 had disease progression (acc. to RECIST 1.1), 1 partial response, 1 stable disease with some extent of tumor shrinkage, and 2 have not had tumor assessment yet. Conclusions: Combination treatment with avelumab 800mg and IMP321 6mg is safe and well tolerated. Cohort 2 will be presented at the meeting. Clinical trial information: NCT03252938 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.3099
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Thoracic radiotherapy plus Durvalumab in elderly and/or frail NSCLC stage III patients unfit for chemotherapy - employing optimized (hypofractionated) radiotherapy to foster durvalumab efficacy: study protocol of the TRADE-hypo trial
    Springer Science and Business Media LLC ; 2020
    In:  BMC Cancer Vol. 20, No. 1 ( 2020-08-26)
    Details
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-08-26)
    Abstract: Non-small cell lung cancer is the most common cause of cancer death worldwide, highlighting the need for novel therapeutic concepts. In particular, there is still a lack of treatment strategies for the group of elderly and frail patients, who are frequently not capable of receiving standard therapy regimens. Despite comprising the majority of lung cancer patients, this group is underrepresented in clinical trials. This applies also to elderly and frail patients suffering from unresectable stage III NSCLC, who are unfit for chemotherapy, and, therefore, cannot receive the standard therapy comprising of radiochemotherapy and the recently approved subsequent durvalumab consolidation therapy. These patients often receive radiotherapy only, which raises the concern of undertreatment. The TRADE-hypo trial aims at optimizing treatment of this patient group by combining radiotherapy with concomitant durvalumab administration, thereby employing the immune-promoting effects of radiotherapy, and determining safety, feasibility, and efficacy of this treatment. Methods/ design In this prospective phase II clinical trial, durvalumab therapy will be combined with either conventionally fractionated (CON-group) or hypofractionated (HYPO-group) thoracic radiotherapy. A safety stop-and-go lead-in phase will assess safety of hypofractionated radiotherapy with respect to severe pneumonitis in small patient cohorts before opening full enrollment. Tumor tissue, blood and stool samples will be collected before and during the study period to investigate the immunological mechanisms responsible for checkpoint inhibitor efficacy and immune-promoting effects of radiotherapy. Discussion Preclinical data suggests that irradiation-induced immunogenicity can be further increased if applied in a hypofractionated setting, potentially boosting the expected synergistic effect with immune checkpoint inhibition in restoring the immune anti-tumor response. If proven safe and efficient, a hypofractionated radiation schedule can provide a considerably more practicable option for the patient. Taking into consideration the intend to develop a combination treatment strategy that can be made available to patients soon after proving to be efficient and the potentially elevated toxicity of a hypofractionated radiotherapy approach, this trial was designed as a two-trials-in-one design. An accompanying translational research program is planned striving to gain insights into the tumor-host biology and to identify suitable biomarkers to predict therapy response. Trial registration Clinicaltrials.gov , NCT04351256 . Registered 17 April 2020, Eudra-CT, 2019–002192-33 . Registered 24 October 2019,
    Type of Medium: Online Resource
    ISSN: 1471-2407
    URL: Article
    DOI: 10.1186/s12885-020-07264-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041352-X
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  • 8
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    Safety Run-In Phase (SRP) cohorts 1 and 2 of the IMMUNIB trial (AIO-HEP-0218/ass): An open-label, single-arm phase II study evaluating safety and efficacy of immunotherapy with PD-L1/L2 inhibition (nivolumab) in combination with receptor tyrosine kinase inhibition (lenvatinib) in advanced stage hepatocellular carcinoma (HCC).
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e16601-e16601
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e16601-e16601
    Abstract: e16601 Background: Immuno-oncology (I-O) drug nivolumab binds to T-cell PD-1 receptor and overcomes tumor induced inhibition of T-cell proliferation and cytokine release caused by PD-L1/L2 interaction. It so enhances the immune system’s natural tumor erasing capacity. In combination with selective targeting of oncogenic signaling pathways by receptor tyrosine kinase inhibitor (TKI) lenvatinib, a markedly improved response rate is expected in patients suffering from advanced stage HCC. Methods: This investigator-initiated phase II trial is designed as a signal generating, single-armed trial. 50 patients are planned in total. Primary endpoints are efficacy (objective response rate acc. to investigator assessed RECIST 1.1) and safety of combination treatment. The trial comprises two successive Safety Run-in Phase (SRP) cohorts, each consisting of 3 consecutively recruited patients, to evaluate safety of defined dose level 0: 240 mg nivolumab i.v. q2w along with 12 mg (≥ 60 kg bw) respectively 8 mg ( 〈 60 kg bw) lenvatinib p.o. qd. This abstract focuses on safety data from SRP cohort 1 and 2 (6 patients) in which all AEs were evaluated after patients received 2 cycles of IMP in dose level 0. In total, 10 patients have been enrolled into the trial up to now. Results: Summarized over both SRP cohorts, no dose limiting toxicities (DLTs) i.e. selected grade 4 events occurred in the six evaluated patients. 2 SAEs (abdominal infection; not IMP-related; grade 3 / fever; IMP-related; grade 1) and 21 AEs have been documented in 6 patients (most common AEs: hypertension [3x (14%); IMP-related], pain [3x (14%) (flank; extremity; unspecified); not IMP-related] - in total 12 AEs IMP-related and 9 AEs not IMP-related). No grade 5 AE, one grade 4 AE (AST increase; IMP-related) and three grade 3 AEs (Abdominal infection and hepatic encephalopathy; not IMP-related / ALT increase; IMP-related) in two patients have been reported. All other AEs were of grades 1 or 2. No patient discontinued treatment during SRP. Conclusions: Combination treatment with nivolumab 240 mg and lenvatinib 12/8 mg was assessed as safe and well tolerated from the data obtained from 6 patients in two cohorts, each received two combination cycles. Regular recruitment was thus opened in January 2020 and is planned to be completed in Q3/2020. Clinical trial information: NCT03841201 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e16601
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 9
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    Pembrolizumab and maraviroc in refractory mismatch repair proficient/microsatellite-stable metastatic colorectal cancer – The PICCASSO phase I trial
    Elsevier BV ; 2022
    In:  European Journal of Cancer Vol. 167 ( 2022-05), p. 112-122
    Details
    In: European Journal of Cancer, Elsevier BV, Vol. 167 ( 2022-05), p. 112-122
    Type of Medium: Online Resource
    ISSN: 0959-8049
    URL: Article
    DOI: 10.1016/j.ejca.2022.03.017
    RVK:
    XA 42017.A
    RVK:
    XA 42017
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 1120460-6
    detail.hit.zdb_id: 1468190-0
    detail.hit.zdb_id: 82061-1
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  • 10
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    The "INSIGHT" Trial: Two new strata of an explorative, open-labeled phase I study evaluating the feasibility and safety of subcutaneous IMP321 injections (LAG-3Ig fusion protein, eftilagimod alpha) combined with either standard-of-care drug therapy or PD-L1 inhibition (avelumab) in advanced-stage solid tumor entities.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. TPS2651-TPS2651
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. TPS2651-TPS2651
    Abstract: TPS2651 Background: The two new strata of the INSIGHT trial evaluate feasibility and safety of s.c. injections of IMP321 (eftilagimod alpha) in combination with either SOC first/second-line drug therapy (Stratum C) or in combination with an PD-L1 inhibitor (avelumab; Stratum D) in advanced stage solid tumors as well as to generate first efficacy data. This proof-of-concept data could build the basis for further clinical studies exploring the therapeutic potential of combinations of active immunotherapy using IMP321 with SOC drug therapies or immunotherapies targeting the PD-1/PD-L1 axis in various solid tumor entities. IMP321 is a MHC class II agonist that activates antigen-presenting cells (primary target cells) and then CD8 T cells (secondary target cells). Activation of the dendritic cell network and subsequent T cell recruitment at the tumor site with IMP321 may lead to enhanced anti-tumor CD8 T cell responses. Thus, especially combinations with PD-1/PD-L1 inhibitors might display interesting effects by activating immune cells and disabling immune inhibitory mechanisms at the same time. Methods: This is a prospective investigator initiated phase I trial consisting of four strata. New stratum C: Patients with solid tumors treated with SOC chemo- or targeted therapy in first or second line receive concomitant s.c. IMP321 injections. This combination is aimed to enhance the immune response against tumor cells compared to chemo-/targeted SOC therapy alone. New stratum D: Patients will receive avelumab i.v. q2w along with s.c. IMP321 injections. This combination is aimed to enhance efficacy by combining IMP321’s activating effects on immune cells with the release of immune inhibitory effects caused by interruption of the PD-1/PD-L1 axis. It is planned to enroll 20 patients in Stratum C and 12 patients in stratum D. Main efficacy endpoint is the overall response rate (RECIST 1.1). Overall recruitment has started; currently (Feb 2019) 14 patients have been enrolled. EudraCT: 2016-002309-20. Clinical trial information: NCT03252938.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.TPS2651
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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