TPS5133 Background: Squamous cell carcinoma of the penis (PeCa) is a rare malignancy with unfavorable outcomes in advanced stage. Since the 1990s, platinum-based chemotherapy has been the standard of care for the first-line treatment of metastatic disease. Unfortunately, it is characterized by a response rate of 30-40%, overall survival (OS) of 17 months and progression free survival (PFS) of 6 months at most. Thus, there is a critical medical need to assess novel systemic strategies for PeCa in the first-line setting, given that current regimens are of a limited clinical benefit while exposing patients to considerable chemotherapy-associated toxicities. In this context, the PD-1 inhibitor pembrolizumab yielded a promising activity in squamous cell carcinomas of various origins. Meanwhile, enfortumab vedotin (EV), a Nectin-4 directed antibody-drug-conjugate, in combination with pembrolizumab has been recently approved for the treatment of metastatic urothelial cancer. The incidence of ≥3 grade adverse events with this regimen was > 55%. Notably, a PD-L1 inhibitor avelumab provided a comparable activity as pembrolizumab but a lower overall rate of endocrine adverse events in patients with urothelial carcinoma. Avelumab monotherapy yielded a response rate of 17% and a median duration of response of 16 months in males with a platinum-refractory PeCa or those unfit for platinum chemotherapy in ALPACA trial. Given that approximately 60% of PeCa tissues express both PD-L1 and Nectin-4, the combination of EV with avelumab represents a potentially synergistic therapeutic strategy, leveraging both direct cytotoxicity and immune-mediated anti-tumor activity through complementary mechanisms of action. Methods: The DEPECA-1 trial is an investigator-initiated, open label, single-arm, multicenter phase II trial, enrolling 25 males with locally advanced or metastatic PeCa at 10 sites in Germany. Patients must be ineligible for curative surgery and not have received any prior systemic palliative therapy. Participants (ECOG ≤ 2) will receive 1200 mg avelumab on day 1 and EV (1,25 mg/kg) on day 1 and day 8 in a 3-week -cycle for a maximum of 24 months and 32 cycles. Primary endpoint is the objective response rate (ORR) assessed per RECIST 1.1. Secondary endpoints include PFS, OS, duration of response (DOR), disease control rate (DCR) and patient-related outcomes. Exploratory analysis comprises tumor biomarker profiling. DEPECA-1 has received regulatory approval on 29 th October 2025. First patient was enrolled on December 16, 2025. Registration IDs: EU CT No. 2025-521644-37-00/NCT07110038. Clinical trial information: NCT07110038 .

LBA4001 Background: The IKF-575 trial investigates the long-standing question about the role of surgical intervention in limited-metastatic gastric / esophagogastric junction cancer after systemic induction therapy. Methods: Previously untreated patients (pts) with limited metastatic disease (retroperitoneal lymph node (RPLN) metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) received 4 cycles of FLOT, + trastuzumab if Her2+ or + nivolumab if PD-L1 positive. Pts without progression after 4 cycles were randomized to receive additional FLOT (Arm B) or radical complete surgical resection of primary and metastases followed by the same treatment (Arm A). It was planned to randomize 176 pts for which 271 pts had to enrolled. The primary endpoint was overall survival in the ITT population using Kaplan-Meier estimates. Recruitment was stopped after enrollment of 183 patients (141 patients randomized) with minimal impact on statistical power, due to a slow enrollment rate. Results: The ITT comprised 139 pts (A, 67; B, 72): 20% had RPLN metastases only, 58% organ metastases only, and 22% had both. Surgery in Arm A (ITT) was performed in 91% of pts and R0-resection rate (primary) was 82%. 30-d and 90-d mortalities in the surgery population were 3% and 8%. At least 4 additional cycles of post-op or post-randomization chemotherapy were achieved in 42% of pts in Arm A vs. 71% of pts in Arm B. The primary endpoint ovrall survival was not met due to increased early mortality in the surgery Arm leading to crossing survival curves with OS 25%- and 75%-Quantiles being 10 vs. 14 months and 65 vs. 41 months for Arms A vs. B, respectively. Pts with RPLN metastases only seemed to benefit most from the surgical approach (mOS, 30 vs. 17 months; 5y OS 38% vs. 19%; still having increased early mortality), while pts showing no response to chemo (mOS, 13 vs. 22 months) or pts with peritoneal disease (mOS, 12 vs. 19 months) derived a detrimental effect. Conclusions: The IKF-575/RENAISSANCE trial is negative but informs future research. Future protocols should focus on pts with RPLN only disease and exclude non-responding pts or those with peritoneal disease. There is a need for strategies against the early mortality caused by chemotherapy interruption. Clinical trial information: NCT02578368 .

TPS4620 Background: UCs are the 6 th most common malignancies in the Western world being localized in the upper (5-10%) or the lower (90-95%) urinary tract. Metastatic UC (mUC), which accounts for 5% of all cases, is associated with a dismal prognosis and prompt progression. So far, the 1 st line therapy for mUC encompassed platinum-based combination regimens. Recent data indicate beneficial patient treatment with immune checkpoint inhibitors. Thus, avelumab was approved for maintenance therapy after progression-free platinum-based chemotherapy for locally advanced (LA) or mUC. Further immune checkpoint inhibitors (e.g. pembrolizumab, atezolizumab, nivolumab) achieved approval or showed promising results for treatment of different patient populations. Eftilagimod alpha (efti) is a soluble LAG-3 fusion protein and a MHC class II agonist activating APCs followed by CD8 T-cell activation. The combination of efti with PD-1/PD-L1 blockade is not yet available and is proposed to enhance efficacy. Based on previous results from the INSIGHT trial and change in treatment landscape we hypothesize that combining avelumab and efti will display clinically relevant efficacy in unresectable LA UC or mUC subgroups with acceptable toxicity. Methods: INSIGHT-005 is a new stratum within the investigator-initiated INSIGHT phase I platform trial ongoing at multiple sites (n=9) in Germany. Patients with unresectable LA UC or mUC will receive efti in combination with avelumab. 30 patients will be enrolled in 3 subgroups: I) Previously untreated, eligible for platinum-based therapy, with PD-L1 CPS≥10; II) Previously untreated, not-eligible for platinum-based therapy, irrespective of the PD-L1 status; III) Suffered disease progression after platinum-based chemotherapy for metastatic disease and did not receive avelumab maintenance therapy, irrespective of the PD-L1 status. Enrolled patients will receive avelumab 800 mg i.v. and efti 30 mg s.c. on the same day Q2W for a maximum of 24 cycles. Tumor evaluation will be performed via CT or MRI every 8 weeks. The primary endpoint of this study is to explore feasibility, safety, and preliminary efficacy of efti when added to avelumab in unresectable LA UC or mUC. Secondary endpoints include safety and efficacy parameters as defined by objective response, time to and duration of response and PFS according to RECIST 1.1, OS and biomarker analyses. First patient was enrolled on 2023-11-29. Currently, recruitment is ongoing. ClinicalTrials.gov ID: NCT03252938 Clinical trial information: NCT03252938 .

BACKGROUND:Eftilagimod alpha (efti) is a major histocompatibility complex class II agonist activating antigen-presenting cells which leads to greater systemic type 1 T helper response and more cytotoxic CD8+ T-cell activation. This phase I trial evaluated the administration of efti, a soluble lymphocyte activation gene-3 (LAG-3) protein, combined with the anti-programmed death-ligand 1 (PD-L1) antibody avelumab in advanced solid tumors.PATIENTS AND METHODS:Patients with heavily pretreated metastatic solid tumors received intravenous avelumab (800 mg) combined with subcutaneously administered efti (6 or 30 mg) for up to 12 cycles, followed by avelumab monotherapy. The primary endpoint was the assessment of the recommended phase II dose (RP2D) of efti in combination with avelumab.RESULTS:Twelve patients with different tumor entities were enrolled (six patients in each cohort). During treatment, no dose-limiting toxicities occurred, and the severity of most adverse events was grade 1 or 2. In total, nine serious adverse events were documented, resulting in a fatal outcome in two cases, but none of them were assessed to be treatment related. Five patients (42%) achieved partial response. The median progression-free survival was 1.96 months and the median overall survival was not reached, with a 12-month survival rate of 75%.CONCLUSION:Subcutaneously administered efti plus avelumab was well tolerated, and efti of 30 mg was determined to be RP2D. The activity is promising and warrants further investigation in future phase II trials.

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/m2, followed by the combination of Tr 1.5 mg/m2 + 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.

3010 Background: Checkpoint inhibition using PD-1/PD-L1 inhibitors does not show clinically relevant activity in MSS/pMMR (Mismatch Repair Proficient) colorectal cancer. Previous work showed that inhibition of CCR5 (C-C chemokine receptor type 5) leads to a macrophage re-polarization towards M1 macrophages within the tumor microenvironment which directly affects immune cell infiltrates. The current phase I trial explores a combined modification of the innate immune system (by CCR 5 blockade) and the adaptive immune system (by PD-1 inhibition) in the treatment of MSS CRC. Methods: 20 patients with metastatic MSS/pMMR colorectal cancer with failure of fluoropyrimidines, oxaliplatin, irinotecan, VEGF antibodies and EGFR antibodies (in ras WT patients) received pembrolizumab 200 mg q21d and maraviroc 300 mg bid cont. for 8 cycles, followed by pembrolizumab monotherapy for a maximum of 24 additional cycles. Imaging was performed every nine weeks (RECIST and irRECIST criteria). Primary endpoint was the feasibility rate (rate of patients receiving the protocol treatment during the core treatment without special event: treatment-related Grade ≥ 3 immune-related abnormalities, treatment-related Grade ≥ 4 AEs or any toxicity-related premature withdrawal of treatment). Secondary endpoints included safety/toxicity, ORR, PFS and OS. Results: 20 patients were enrolled. The median number of applied cycles was 3.5 for pembrolizumab and 3.5 for maraviroc. Two patients completed the core treatment period with pembrolizumab and started maintenance treatment. The feasibility rate was 94.7% (90% CI 77.4 to 99.7%), with one patient experiencing a special event. Except this grade 4 event (hyperglycemia) no ≥ 3 treatment-related toxicities were observed. According to irRECIST criteria one patient showed a partial response and one a stable disease as best response, resulting in an irDCR of 10.5%. Median PFS according to irRECIST was 2 months (CI 95%, 2 to 3), median OS 9 months (CI 95%, 6 to 20). Conclusions: Therapy with pembrolizumab and maraviroc was feasible and showed a beneficial toxicity pattern. Clinical activity in MSS CRC patients was limited, however prolonged disease stabilizations were observed in single patients and overall survival was higher than expected in this heavily pretreated population. Clinical trial information: NCT03274804 .

Immuno-oncology drug nivolumab binds to T-cell PD-1 receptor and overcomes tumor induced inhibition of T-cell proliferation and cytokine release caused by PD-L1/2 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 lenvatinib, a markedly improved response rate is expected in patients suffering from advanced stage HCC. The investigator-initiated phase II single-armed 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) resp. 8 mg (< 60 kg bw) lenvatinib p.o. qd. Primary endpoints are efficacy (ORR acc. to investigator assessed RECIST 1.1) and safety of combination treatment. 50 patients are planned in total. Up to now, 21 patients have been enrolled. 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. Summarized over both SRP cohorts, no dose limiting toxicities i.e. selected grade 4 events occurred. 2 SAEs (abdominal infection; not IMP-related; grade 3 / fever; IMP-related; grade 1) and 21 AEs have been documented (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. 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.

Strata (St) A / B of the INSIGHT study evaluate feasibility of intratumoral (i.t.) and intraperitoneal (i.p.) IMP321 monotherapy in advanced solid tumors. The MHC class II agonist activates antigen presenting cells followed by CD8 T cell activation. This is an investigator-initiated study with currently 4 St: i.t. (A) or i.p. IMP321 (B); s.c. IMP321 with SOC (C) or combined with avelumab (D). Here we focused on St A / B. In St A, patients (pts) received i.t. injections (inj) with IMP321 escalation 6-12-24-30mg in cohort (coh) 1 and the max. tolerated dose (MTD) in coh 2. In St B, pts with peritoneal carcinomatosis received i.p. IMP321 (dose escalation 1-3-6-12-30mg in coh 1 and MTD in coh 2). In both St pts with a benefit after the last inj. were offered s.c. IMP321 for up to 52 weeks. Main endpoint was safety. Recruitment has been completed with 8 pts treated in St A (coh 1: 3 pts. [2 gastric cancer, 1 peritoneal mesothelioma]; coh 2: 5 pts [cancer of head & neck, colon {2}, papilla, lung]) and 4 pts in St B coh 1 (2 gastric, 2 colon cancer). No dose limiting toxicities occurred. 14 serious adverse events (SAEs) have been reported: 8 in St A (2 in 1 pt of coh 1, 6 in 4 pts of coh 2) and 6 in 3 pts of St B coh 1. 1 SAE in coh 2 of St A was related to study procedure (sudden death NOS grade 5). 1 AESI (St A coh 1) probably related to IMP321 (chills grade 3). Of the heavily pretreated pts, 5 had stable disease (SD) (3 gastric, 2 colon cancer), 5 progressive disease (RECIST) and 2 clinical progression. 2 of the SD pts. had PFS of 3mo (1 gastric St A; 1 colon St B) and 2 SD pts. had PFS of 4mo (2 gastric St B). The SD gastric cancer pt of St A with PFS of 3 mo had an OS of 28 mo with increase of PD-L1 in the immune cells from 20% at baseline (BL) to 30% (D29 + D71). 3 SD pts with gastric cancer showed high CD45, CD163 expression at BL (tissue). Blood cytokine profile: 1 SD St B pt showed a significant increase in CXCL10, 4h - 24h after inj. measured on D1/D29, with similar peaks for IFN ɣ, combined with a moderate increase in CD4 and CD8 cells. Increase in IFN ɣ with additional Nk-cells was also seen in 1 SD St A pt. Intratumoral and intraperitoneal IMP321 can be safely administered up to 30 mg with signals of clinical and cytokine activity.

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 .

Treatment of soft tiusse sarcoma (STS) with the combination of trabectedin and the anti-PD1 antibody nivolumab suggests to be a promising treatment approach as the combination produces a synergistic antitumor effect in a murine model of ovarian cancer. Moreover, the antitumor activity of trabectedin is partially mediated by macrophage depletion and different immunologic effects. Thus, it seems reasonable to evaluate the efficacy and safety of trabectedin plus nivolumab as a second-line option in anthracycline-pretreated sarcomas. This is a prospective phase II NiTraSarc trial consisting of two parallel groups: Group A includes patients with liposarcoma or leiomyosarcoma (abbreviated as L-sarcomas; n=55); whereas Group B comprise patients with non-L-sarcomas (n=37). Patients in both groups have unresectable or metastatic STS and have received a prior anthracycline-containing regimen. Initially, the enrolled patients are treated with three cycles of trabectedin monotherapy, given every three weeks (q3w), followed with the combination of trabectedin (1.5 mg/m2) plus nivolumab (240 mg) starting from cycle four (“late combination cohort”) for up to a total of 16 cycles q3w. A pre-planned interim safety evaluation was performed once nine patients had completed the third trabectedin plus nivolumab combination cycle. Due to absence of serious safety issues with this potentially more efficient therapy, the trial design was amended moving the start of combination therapy after only one cycle of trabectedin monotherapy (“early combination cohort”). All patients undergo tumor assessments after Cycle 3 and afterwards every 9 weeks ± 1 week until disease progression. Primary efficacy endpoint of the trial is progression-free survival (PFS) rate after 6 months (PFS-6) according to RECIST v.1.1. Secondary endpoints are overall response rate, overall survival, PFS and duration of disease stabilization. In May 2020, 82 of planned 92 patients have been enrolled. This trial is supported by PharmaMar and Bristol-Myers Squibb with drug and funding. NCT03590210; EudraCT: 2017-001083-38. Review by PharmaMar and Bristol-Myers Squibb. Sponsor of the Study according to AMG is Universitätsmedizin Greifswald, Fleischmannstr. 8, 17475 Greifswald, Germany. Representative of the Sponsor: Dr. med. Daniel Pink Klinik für Hämatologie, Onkologie und Palliativmedizin, Sarkomzentrum Berlin-Brandenburg, HELIOS Klinikum Bad Saarow, Pieskower Str. 33, 15526 Bad Saarow, Email: [email protected] PharmaMar & Bristol-Myers Squibb (drug and funding).

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 .

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 .

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.

TPS3129 Background: The INSIGHT study evaluates feasibility and safety of intratumoral and intraperitoneal injections of IMP321 (mono-agent) for the treatment of 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 active immunotherapy with IMP321 by direct injection into the tumor mass or the peritoneal space. Furthermore, safety and efficacy of combining standard-of-care (SOC) chemo(immuno-)therapies with IMP321 subcutaneous (s.c.) injections in various solid tumor entities will be assessed. IMP321 is a soluble form of the LAG-3 T cell surface receptor with a dual mode of action (MOA) consisting of activation of antigen presenting cells (primary MOA) and prevention of exhaustion of activated T-cells (secondary MOA at high local concentration). Methods: This is a prospective investigator initiated phase I trial consisting of three strata. Stratum A: Pretreated patients with solid tumors which are accessible for repeated injections and biopsies receive q2w intra-tumoral injections of IMP321 as a monotherapy. Stratum B: Pretreated patients with solid tumors and additional peritoneal carcinomatosis receive q2w intra-peritoneal IMP321 injections via direct injection or a silicon catheter. Both strata are performed in a classical 3 patient cohort study design consisting of intra-patient dose-escalation and consolidation cohorts. Stratum C: Patients with solid tumors treated with SOC chemo(immuno-)therapy in first or second line receive concomitant s.c. IMP321 injections. It is planned to enroll 9 patients each in Stratum A and Stratum B and 20 patients in Stratum C. Main efficacy endpoint is the overall response rate according to RECIST criteria. The trial is accompanied by an extensive biomarker research program. Recruitment has started; currently (Feb 2018) 4 patients have been enrolled (3 Stratum A, 1 Stratum B). Up to now, no DLTs have been observed. ClinicalTrials.gov Identifier: NCT03252938; EudraCT: 2016-002309-20. Clinical trial information: NCT03252938.