Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients will receive maintenance therapy with 4 cycles of Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg every three weeks (Q3W)(induction phase) followed by Nivolumab 480 mg every 4 weeks (Q4W)(consolidation phase) until unacceptable toxicity, disease progression (PD), investigator ́s decision, patient's consent withdrawal or death by any cause, whichever occurs first.

Nivolumab at 1 mg/kg by intravenous (IV) infusion on D1 of each cycle. Nivolumab at a fixed dose of 480 mg by intravenous (IV) infusion on D1 of each cycle. The maximum duration of treatment with nivolumab will be 2 years, and patients will discontinue treatment at any time in case of unacceptable toxicity, disease progression (PD), investigator ́s decision, patient's consent withdrawal or death by any cause, whichever occurs first.

Ipilimumab at 3 mg/kg by intravenous (IV) infusion on D1 of each cycle.

Federico Nepote

Pau Donate

A responsible person designated by the Sponsor

Principal investigator selected by the sponsor, M.D.; Ph.D.

A responsible person Designated by the Sponsor

A Principal Investigator Designated by the Sponsor, M.D.; Ph.D.

A responsible person delegated by the sponsor

Guillermo de Velasco

Immunotherapy has improved clinical outcomes in metastatic urothelial carcinoma (mUC). Second-line treatment after progression to platinum-containing chemotherapy with immune checkpoint inhibitors (ICIs) have antitumor activity in advanced / metastatic UC and provide favorable safety profiles when compared with chemotherapy The study aims to determine if Nivolumab plus Ipilimumab maintenance therapy is effective in delaying disease progression in patients with unresectable locally advanced or metastatic urothelial cancer that did not progress during or following completion of first-line chemotherapy. Vexillum plans to recruit patients that achieve clinical benefit from first-line chemotherapy and may be candidates for maintenance immunotherapy to consolidate this benefit.

All enrolled patients should have received first-line chemotherapy and not progressed. After a treatment-free interval of 3-12 weeks from chemotherapy, patients will receive maintenance therapy with 4 cycles of Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg every three weeks (Q3W)(induction phase) followed by Nivolumab 480 mg every 4 weeks (Q4W)(consolidation phase) until unacceptable toxicity, disease progression (PD), investigator ́s decision, patient's consent withdrawal or death by any cause, whichever occurs first.

* Induction phase (Total of 4 cycles Q3W)

  * Nivolumab at 1 mg/kg by intravenous (IV) infusion on D1 of each cycle.
  * Ipilimumab at 3 mg/kg by intravenous (IV) infusion on D1 of each cycle.
* Consolidation phase (Cycles Q4W) ○ Nivolumab at a fixed dose of 480 mg by intravenous (IV) infusion on D1 of each cycle. The maximum duration of treatment with nivolumab will be 2 years, and patients will discontinue treatment at any time in case of unacceptable toxicity, disease progression (PD), investigator ́s decision, patient's consent withdrawal or death by any cause, whichever occurs first.

Study of NIVOLUMAB/IPILIMUMAB Maintenance in Unresectable Locally Advanced or Metastatic Urothelial Cancer

Phase II Non Randomized Clinical Trial of NIVOLUMAB/IPILIMUMAB Maintenance Following First-line Chemotherapy in Unresectable Locally Advanced or Metastatic Urothelial Cancer.

PFS is defined as the time from the first dose of study treatment date until the first documentation disease progression or death from any cause, whichever occurs first. A subject who has not confirmed progression will be censored at the last known disease evaluation. Patients who have not progressed and start a new line of treatment will be censored at the date of the last adequate tumor assessment prior to starting the next line of therapy. Estimated by Kaplan Meier.

subgroup analysis of PFS. Same definition of PFS as Outcome 1 applies.

Time from the first dose of study treatment date to the date of death and the proportion/percentage of patients alive at the end of follow-up. A subject who has not died will be censored at the last known date alive. Estimated by Kaplan Meier

Percentage/proportion of patients with complete response (CR) or partial response (PR), according to ORR definition for the trial, or maintained stable disease (SD) as their overall best response throughout the study period, assessed by imaging follow-up (CT scan/MRI) and RECIST 1.1 criteria. Stable disease should be maintained for at least 4 months to be considered as a CBR event.

Time from first confirmed response (CR or PR), according to ORR definition for the trial, to the date of the documented PD as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first.

defined as the time from first dosing date of chemotherapy until the first documentation disease progression or death from any cause, whichever occurs first.

Time from first dosing of chemotherapy date to the date of death and the proportion/percentage of patients alive at the end of follow-up.

Number of patients experiencing adverse events from the total of patients exposed to study drug

Number of patients experiencing adverse events related to the study treatment from the total of patients exposed to study drug

Patient reported outcomes assessed through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), version 3 and the EuroQoL five-dimensions, 5 level (EQ- 5D-5L) questionnaire. Median scores for both questionnaires will be provided.

Assessed by the investigator by imaging follow-up (CT scan/MRI) using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. This will be considered as the percentage/proportion of patients with confirmed complete response (CR) or partial response (PR) as their overall best response throughout the study period. Objective responses will be assessed by the investigator according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.

Bristol-Myers Squibb

Spanish Oncology Genito-Urinary Group

Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Rare Diseases

Adenocarcinoma

Stomach Neoplasms

Neoplasm Metastasis

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Stomach Cancer

Oxaliplatin

Capecitabine

Antimetabolites

Subjects enrolled are treated with oral capecitabine 1000mg per m2 bid for two weeks（every 3 weeks）and intravenous oxaliplatin 130mg per m2（every 3 weeks）in combination with sintilimab 200mg (every 3 weeks)

oral capecitabine 1000mg per m2 bid d1-14, intravenous oxaliplatin 130mg d1 per m2, sintilimab 200mg (every 3 weeks)

sintilimab

Qiu Li, M.D.

This study aims to evaluate the efficacy and safety of Sintilimab plus CAPOX in the conversion therapy for patients with unresectable locally advanced or limited metastatic adenocarcinoma of the stomach or esophagogastric junction

In a variety of solid tumors such as colorectal cancer, it has been confirmed that some selected advanced patients still have a chance to cure through multidisciplinary treatment. Because of the poor biological behavior of gastric cancer, few people with advanced gastric cancer can benefit from local treatment, and there are fewer related studies. However, retrospective and small sample size prospective phase II clinical studies have also shown that unresectable locally advanced and some selected limited distant metastatic gastric and gastric junction adenocarcinoma patients may also achieve long-term survival through multimodal treatment strategies. The triple drug regimens were often used as conversion regimens in previous studies. Although the efficiency was improved, the R0 resection rate was only about 60%, the disease-free survival was about 10 months, and the toxicity was high. In order to improve the survival of these patients, more effective and less toxic treatment regimens are urgently needed. Objective response rate was 76.5% with anti-PD-1 antibody nivolumab plus CapeOX. The investigators predict that this regimen will achieve good results in the conversion treatment of advanced gastric cancer. The investigators intend to carry out this study to evaluate the efficacy and safety of Sintilimab plus CAPOX in the conversion therapy for patients with unresectable locally advanced or limited metastatic adenocarcinoma of the stomach or esophagogastric junction. The primary objectives are 12-month progression- free survival (PFS) rate. Secondary objectives include safety, objective response rate (ORR), R0 resection rate , tumor regression grading（TRG）, progression- free survival (PFS) ，overall survival (OS) and exploratory biomarker assessment. Subjects enrolled are treated with oral capecitabine 1000mg per m2 bid for two weeks（every 3 weeks）and intravenous oxaliplatin 130mg per m2（every 3 weeks）in combination with sintilimab 200mg (every 3 weeks) for 3 cycles. After 3 cycles of treatment, the tumor was evaluated. The clinical efficacy was evaluated as CR\\PR\\SD. Patients with SD,PR,CR will be treated with surgery. 36 patients will be included in this study

Conversion Therapy With Sintilimab Plus CAPOX in Patients With Unresectable Locally Advanced or Limited Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction

An Exploratory Study of Conversion Therapy With Sintilimab Plus CAPOX in Patients With Unresectable Locally Advanced or Limited Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction

Proportion of patients with Progression Free Survival in 12-month

Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients

Proportion of patients with complete resection

Assessing the grade of tumor regression according to tumor regression grading criteria

Defined as the time from the date of enrollment to the first date of documented objective progression disease (defined by RECIST 1.1) or of death from any cause

Defined as the time from the date of enrollment to the date of death from any cause

Any adverse events related with treatment with Sintilimab plus CAPOX

Sichuan University

Professor

Skin and Connective Tissue Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Gemcitabine

Carboplatin

* Carboplatin Area Under the Curve (AUC) 2 mg/mL/min intravenous (IV) on days 1 and 8, every 3-week cycles.
* Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles.
* Nadunolimab escalation (DL -1: 0.5 mg/Kg, DL 1: 1 mg/kg, DL 2: 2.5 mg/kg), DL 3: 5 mg/kg IV on days 1 and 8, every 3-week cycles.

* Carboplatin AUC 2 mg/mL/min IV on days 1 and 8, every 3-week cycles.
* Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles.
* Nadunolimab Recommended Phase II Dose (RP2D) mg/kg IV on days 1 and 8, every 3-week cycles

* Carboplatin AUC 2 mg/mL/min IV on days 1 and 8, every 3-week cycles.
* Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles.

Carboplatin Area Under the Curve (AUC) 2 mg/mL/min intravenous (IV) on days 1 and 8, every 3-week cycles

Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles

Nadunolimab escalation (DL -1: 0.5 mg/Kg, DL 1: 1 mg/kg, DL 2: 2.5 mg/kg), DL 3: 5 mg/kg IV on days 1 and 8, every 3-week cycles.

Nadunolimab

CANTARGIA AB

Chief Investigator

Chief Medical Officer

Triple negative breast cancer (TNBC) represents approximately 15% of all breast cancers (BC) worldwide. The term triple negative means that tumor growth is not stimulated by the hormones estrogen and progesterone, nor by the HER2 protein, so unlike other types of BC, TNBC, which is an aggressive form of BC, does not have specific effective therapies available being the least common form of BC and the most difficult to treat.

Advanced or metastatic TNBC is treated with combinations of platinum-based chemotherapy with taxanes or gemcitabine with a 5-year survival rate of 12%. Recent studies have shown that TNBC expresses Interleukin 1 Receptor Accessory Protein (IL1RAP) at higher levels than other forms of BC.

Nadunolimab is a fully humanized monoclonal antibody that blocks the signals that occur within the cell produced by IL1RAP protein, thereby impairing the cancer cells' ability to secrete tumor stimulating substances, in turn reducing the tumor, inflammation and tumor progression. On the other hand, it is an antibody designed to activate the immune system to fight cancer cells.

This clinical trial is divided into two phases, phase Ib in which it is expected to include up to 18 patients and phase II in which it is expected to include 98 patients. The main purpose of phase Ib is to ensure that the combination of nadunolimab plus chemotherapy (gemcitabine plus carboplatin) is safe and determine the highest dose of nadunolimab that can be given safely without causing serious side effects. If the pre-specified objectives in this part are achieved, the trial will be expanded to a randomized phase II, to evaluate the efficacy of the combination of nadunolimab plus gemcitabine plus carboplatin, compared to a control group that will receive gemcitabine plus carboplatin only.

Triple negative breast cancer (TNBC) represents approximately 15% of all breast cancers worldwide and is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. TNBC is more common in African American women, in premenopausal women and in BRCA1/2 mutation carriers. TNBC presents the worst outcomes of all breast cancer (BC) subtypes with a 5-year overall survival (OS) of 78.5%, even when the analyses are adjusted for age, disease stage, race, tumor grade and adjuvant chemotherapy (CT). One in three TNBC patients will develop distant metastases, which typically occurs within the first 3 years of initial diagnosis, and persistently, one in five TNBC patients will succumb to their metastatic disease in less than 5 years. The 5-year survival rates for localized, regional, and metastatic TNBC are 91%, 65%, and 12% , respectively. The dismal prognosis of high-risk, locally advanced and metastatic TNBC highlights an unmet need for an improved survival in these patients. Another reason for the poor outcomes associated with TNBC is the lack of effective targeted therapies. As a result, standard cytotoxic CT remains the backbone of systemic therapy in TNBC patients.

Further attempts to classify TNBC into distinct subtypes based on unique tumor/tumor microenvironment (TME) cellular signatures and messenger ribonucleic acid (mRNA) expression profiles may provide relevant information about the molecular drivers, actionable therapeutic targets and effective therapy selection. Based on the PAM50 gene expression profile, 78.6% of TNBC have significant overlap with the basal-like molecular subtype. The remaining gene expression profiles of TNBC (21.4%) may be further subclassified as normal-like (7%), HER2-enriched (7.8%), luminal B (4.4%), and luminal A (2.2%). Even though the assessment and characterization of TNBC into molecular subtypes is not currently performed clinically on a routine basis, these sub-classifications based on unique cellular signatures and global RNA expression profiles may provide therapeutic insights for each specific subset of TNBC patients.

Current available treatments for advanced TNBC are palliative in nature and are based mostly on the use of cytotoxics. Recently poly Adenosine diphosphate (ADP) ribose polymerase inhibitors (PARPi), (olaparib, talazoparib) have shown efficacy in patients with germline BRCA (gBRCA) mutant tumors, with olaparib and talazoparib already approved in the advanced setting. Atezolizumab in combination with nab-paclitaxel has been approved for patients with unresectable locally advanced or metastatic TNBC whose tumors express programmed death-ligand 1 (PD-L1). Pembrolizumab, in combination with CT (paclitaxel, or nab-paclitaxel, or gemcitabine plus carboplatin), has been granted accelerated approval by the Food and Drug Administration (FDA) for locally recurrent unresectable or metastatic TNBC not previously treated with CT in the metastatic setting and with PD-L1 expression (Combined Positive Score (CPS) ≥ 10) as determined by the PD-L1 immunohistochemistry (IHC) 22C3 pharmDx (Dako North America, Inc.), also approved by the FDA as a companion diagnostic. Despite of these interesting results, new treatments are necessary for patients with TNBC.

Platinum agents have recently become an important treatment option in the management of TNBC, especially in patients with BRCA mutations or PD-L1-negative or who have progressed to immune checkpoint inhibitors, as carboplatin demonstrated comparable efficacy and a more favorable toxicity profile compared with docetaxel. Platinum-based regimens are particularly appealing in TNBC based on their DNA-damaging mechanism of action , due to the high genomic instability observed on this type of BC, particularly in patients harbouring gBRCA1/2 mutations or "BRCAness" (homologous recombination repair defects in the absence of gBRCA1/2 mutations). The TNT trial showed that carboplatin is a particularly active drug in gBRCA mutated BC patients. In the metastatic setting, interesting activity has been reported with the gemcitabine plus carboplatin combination (dose of 1,000 mg/m2 and area under the curve \[AUC\] 2 mg x min/mL, respectively, on days 1 and 8 of each 3-week cycle), in both phase II and III trials testing the role of iniparib in advanced TNBC with a median progression-free survival (PFS) of 3.1 and 4.1 months, and a median OS of 7.7 and 11.1 months, respectively. In exploratory analyses by line of therapy in the phase III trial, patients who received first line treatment had a median PFS of 4.6 months and a median OS of 12.6 months; for those patients treated in second line, the median PFS was 2.9 months and the median OS was 8.1 months. Regarding the tumor response according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 with confirmation of response and independent central review, the following percentages were reported: a) complete response (CR) 1.6%; b) partial response (PR) 29%; c) stable disease (SD) 35% (lasting more than 6 months in 5.4%); d) progressive disease (PD) 24%; and e) nonevaluable 5.4%. The overall response rate (ORR) was 30% (95% Confidence Interval (CI), 25-36%) and the clinical benefit rate (CBR) with SD \> 6 months, 36%. If we consider the Treatment Emergent Adverse Events (TEAEs) published in 2014, the most frequent AEs included neutropenia 65% (Grade \[G\] 3/4 53%), fatigue 63% (G 3/4 6%), anemia 62% (G 3/4 22%), nausea 59% (G 3/4 3%), thrombocytopenia 54% (G 3/4 24%), constipation 42% (G 3/4 \< 1%), and vomiting 31% (G 3/4 1%). Data from the tnAcity trial in the first line setting showed a median PFS of 6.0 months and a median OS of 12.6 months in the control arm treated with gemcitabine 1,000 mg/m2 plus carboplatin AUC 2 mg x min/mL, on days 1 and 8 of 3-week cycles. Another efficacy results published include the 12-month PFS rate (11%), ORR (44% \[CR 8%, PR 36%\]), median duration of response (DoR) (5.0 months), SD ≥ 4 months (32%), PD as best response (21%). At least one G ≥ 3 AE was reported in 84% of patients and at least one serious AE in 39% of patients with this combination. The most frequently observed G ≥ 3 AEs were neutropenia (52%), thrombocytopenia (28%), anemia (27%), leukopenia (11%), fatigue (3%) and peripheral neuropathy (2%). The meta-analysis with data from more than 4,500 patients supports the use of platinums in Advanced Breast Cancer (ABC) and this recommendation is considered in current international practice guidelines ABC.

Phase Ib: Single-arm (dose-escalation 3+3 design).

* Carboplatin Area Under the Curve (AUC) 2 mg/mL/min intravenous (IV) on days 1 and 8, every 3-week cycles.
* Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles.
* Nadunolimab escalation (Dose Level (DL) -1: 0.5 mg/Kg, DL 1: 1 mg/kg, DL 2: 2.5 mg/kg), DL 3: 5 mg/kg IV on days 1 and 8, every 3-week cycles.

Phase II: Randomized 1:1, non-comparative, open-label.

Patients randomized to arm A will receive:

* Carboplatin AUC 2 mg/mL/min IV on days 1 and 8, every 3-week cycles.
* Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles.
* Nadunolimab Recommended Phase II Dose (RP2D) mg/kg IV on days 1 and 8, every 3-week cycles.

Patients randomized to arm B will receive:

* Carboplatin AUC 2 mg/mL/min IV on days 1 and 8, every 3-week cycles.
* Gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3-week cycles.

Nadunolimab in Combination With Gemcitabine Plus Carboplatin in Patients With Advanced Triple Negative Breast Cancer.

A Randomized Non-comparative Open-label Phase 1b/2 Study of Nadunolimab in Combination With Gemcitabine Plus Carboplatin in Patients With Advanced Triple Negative Breast Cancer. "TRIFOUR Study"

The Study Protocol and the Statistical Analysis Plan (SAP) will be shared on the ClinicalTrials.gov web site. Also, results will be publish on congresses and manuscripts in scientific journal.

DLT is defined according to the NCI-CTCAE version 5.0 as any of the following events considered by investigator to be related to investigational treatment:

1. Grade (G) 5 Treatment Emergent AE
2. G ≥ 3 neutropenia + fever and/or infection (single temp. \> 38.3°C or sustained temp. ≥ 38°C \>1 hour)
3. G 4 neutropenia \> 7 days
4. G 4 thrombocytopenia \> 3 days
5. G ≥ 3 thrombocytopenia \> 7 days or accompanied by G 2 bleeding or platelet transfusion
6. Delay in the initiation of Cycle 2 \> 7 days from the calculated start date due to a lack of adequate recovery of treatment-related hematological or non-hematological toxicity
7. G ≥ 3 AE with permanent discontinuation of any of the study drugs
8. Elevations of bilirubin and transaminases meeting Hy's Law criteria
9. G 4 laboratory abnormalities discussed with the Medical Coordinators, Sponsor and GEICAM
10. G ≥ 3 non-hematological toxicity
11. G 2 toxicity considered a dose limiting

Tumor response is assessed according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1 as per investigators' assessment.

ORR is defined as the rate of Complete Response (CR) plus Partial Response (PR) according to RECIST version 1.1, out of the patients who receive at least one dose of treatment and have measurable disease. These results will be calibrated against the ORR in the control arm.

CBR is defined as the rate of a Complete Response (CR) plus Partial Response (PR) plus Stable Disease (SD) lasting ≥ 24 weeks, according to RECIST v1.1 and as per investigator's assessment out of enrolled patients. n. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an \>=30% decrease in the sum of the longest diameter of target lesions; SD is defined as a failure to meet criteria for CR or PR in the absence of progressive disease

DCR is defined as the rate of CR, PR plus SD of any duration, according to RECIST v1.1 and as per investigator's assessment out of enrolled patients.

DoR assessed according to RECIST v1.1, is defined as the time from the date of first documentation of overall response (CR or PR) to the date of first documented progressive disease (PD), or death from any cause, whichever occurs first. PD is defined using RECIST, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

PFS according to RECIST v1.1 as per the investigator's assessment. It is defined as the time from the date of enrolment to the date of PD or death from any cause, whichever occurs first.

PD is defined using RECIST, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions within 6 and 12 months.

PFS according to RECIST v1.1 as per the investigator's assessment. It is defined as the time from the date of enrolment to the date of PD or death from any cause, whichever occurs first at 6 and 12 months

OS is defined as the time from the date of enrolment to the date of death from any cause.

Proportion of patients alive at 12 and 18 months; on the basis of the median duration of OS observed.

Response parameters per Guidelines for Response Criteria for Use in Trials Testing Immunotherapeutics (iRECIST) criteria in patients who receive treatment beyond PD by RECIST 1.1 Tumor response is assessed using iRECIST. iORR is defined as the percentage of patients with a Immune Complete Response (iCR) or Immune Partial Response (iPR) out of the patients from the efficacy population. Per iRECIST, iCR is defined as the disappearance of all measurable and non-measurable lesions, and lymph nodes must decrease to \< 10 mm in short axis; iPR is defined as an \>=30% decrease in total measured tumor burden relative to baseline; Immune Overall Response (iOR) = iCR + iPR.

Response parameters per iRECIST criteria in patients who receive treatment beyond PD by RECIST 1.1 Tumor response is assessed using iRECIST. iCBR is defined as the rate of a Immune Complete Response (iCR) plus Immune Partial Response (iPR) plus Immune Stable Disease (iSD) lasting ≥ 24 weeks iCR is defined as the disappearance of all target lesions; iPR is defined as an \>=30% decrease in the sum of the longest diameter of target lesions; iSD is defined as a failure to meet criteria for iCR or iPR in the absence of progressive disease

Response parameters per iRECIST criteria in patients who receive treatment beyond PD by RECIST 1.1 iDCR is defined as the rate of iCR, iPR plus iSD of any duration

Response parameters per iRECIST criteria in patients who receive treatment beyond PD by RECIST 1.1 iPFS is defined as the time from the date of enrolment to the date of immuno Progressive Disease (iPD) or death from any cause, whichever occurs first.

It will be assessed by the frequency, severity and nature of AEs, serious adverse event (SAE), changes in vital signs and standard clinical and laboratory tests (haematology, serum chemistry, and urine). The severity of AEs will be graded by the NCI CTCAE version 5.0 and the AE terms will be coded by the current version of the Medical Dictionary for Regulatory Activities (MedDRA).

CFB in the global health status (GHS) score and each scale of the EORTC quality of life questionnaire (QLQ) -C30 questionnaire.

Patient reported outcomes of health-related quality of life will be assessed using the EORTC QLQ-C30 questionnaire and analyzed on the QoL population.

Published scoring manuals and guidelines will be used to generate scale scores and handle missing data. Descriptive statistics for actual values will be tabulated at each scheduled time point.

CFB will be presented at each scheduled time point for the GHS score and each of the functionals and symptoms scales from the EORTC QLQ-C30 questionnaires.

Longitudinal analysis of scores will be performed using linear mixed models.

CFB in the global health status (GHS) score and each scale of the EORTC QLQ-C30 questionnaire.

Patient reported outcomes of health-related quality of life will be assessed using the EORTC QLQ-C30 questionnaire and analyzed on the QoL population.

Published scoring manuals and guidelines will be used to generate scale scores and handle missing data. Descriptive statistics for actual values will be tabulated at each scheduled time point.

TTD will be assessed using the Kaplan-Meier method. The median event time and 95% CI for the median will be estimated if reached. TTD will be censored at the date of the last QoL assessment prior to the start of a new therapy.

It will be assessed by incidence of different type of dose modifications, discontinuations due to AEs, number of administered cycles, etc.

Blood samples for nadunolimab serum concentration analysis will be collected prior to each nadunolimab infusion and 1 hour after the end of each nadunolimab infusion on Day 1 and on Day 8 (all cycles), and at post-treatment visit (30 (±3) days after the last dose of study treatment.

The formation of ADAs against nadunolimab will be assessed in blood samples collected prior to nadunolimab administration on Day 1 of each cycle and post-treatment visit.

Immunogenicity will be evaluated by determination of the presence of ADAs as measured in serum by a tiered testing approach involving an initial screening assay, confirmation, and titration of confirmed positive samples. Samples will be banked so that further characterisation of the effect of ADAs upon nadunolimab binding to its target antigen may be undertaken.

Characterisation of banked samples will include assessment of neutralising antibodies for samples that have been confirmed positive for ADA

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of NIVOLUMAB/IPILIMUMAB Maintenance in Unresectable Locally Advanced or Metastatic Urothelial Cancer	NCT05219435	Urothelial Canc...	Nivolumab Ipilimumab	18 Years -	Spanish Oncology Genito-Urinary Group
Conversion Therapy With Sintilimab Plus CAPOX in Patients With Unresectable Locally Advanced or Limited Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction	NCT04263870	Gastroesophagea... Stomach Adenoca... Locally Advance... Metastatic Gast...	sintilimab	18 Years - 75 Years	Sichuan University
Nadunolimab in Combination With Gemcitabine Plus Carboplatin in Patients With Advanced Triple Negative Breast Cancer.	NCT05181462	Triple Negative...	Carboplatin Gemcitabine Nadunolimab	18 Years -	Cantargia AB

Spots Global Cancer Trial Database for unresectable locally advanced