Cancer of unknown primary site (CUP-Syndrome), relapsed/refractory to platinum-based chemotherapy MedDRA version: 21.0 Level: LLT Classification code 10007460 Term: Carcinoma of unknown primary System Organ Class: 100000004864
Conditions
Interventions
Trade Name: YERVOY
Pharmaceutical Form: Concentrate and solvent for concentrate for solution for infusion
INN or Proposed INN: IPILIMUMAB
Current Sponsor code: BMS-734016
Concentration unit: mg/ml mil
Sponsors
University Heidelberg, Med. Fac. repr. by University Hospital and its Commercial Managing Director
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Signed Informed Consent Form - Able and willing to comply with the study protocol - Age = 18 years at time of signing Informed Consent Form - Histologically-confirmed disseminated or advanced unresectable CUP diagnosed according the criteria defined in the 2015 ESMO Clinical Practice Guidelines for CUP. Acceptable disease histology includes: • Adenocarcinoma of unknown primary site (ACUP) • Poorly differentiated adenocarcinoma of unknown primary site • Poorly differentiated carcinoma of unknown primary site • Squamous cell carcinoma of unknown primary site (SCUP) - At least one lesion that is measurable according to RECIST v1.1 by CT/MRI - Availability of a tumor FFPE block either fresh or archival if obtained = 6 months at Screening that is sufficient for generation of a TruSight Oncology 500 (TSO500) panel at the central reference pathology laboratory or pre-existing result of a TMB analysis from routinely performed panel sequencing using the TSO500 panel at the MPZ, Institute of Pathology, University Heidelberg, which must not be older than =65 years) yes F.1.3.1 Number of subjects for this age range 97
Exclusion criteria
Exclusion criteria: - Subjects with any of the specific non-CUP neoplasms identified in the ESMO CUP guidelines (Fizazi et al. 2015) - Subjects belonging to any of the following subsets of CUP with favorable prognoses - Known presence of brain or spinal cord metastasis, as determined by CT or magnetic resonance imaging (MRI) evaluation during screening. As an exception, patients with brain metastases are allowed to be included if all of the following five criteria are met: (i) the total number of brain metastases is 3 or less, (ii) brain metastases were / are asymptomatic, (iii) brain metastases have been completely surgically resected or completely treated with stereotactic radiosurgery (iv) there was / is no indication for whole-brain irradiation, (v) a brain MRI or high-resolution CT-scan at screening shows no evidence of residual disease - Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis, current alcohol abuse, or cirrhosis - HIV infection - Positive for hepatitis C virus (HCV) infection at screening - Positive for hepatitis B surface antigen (HBsAg) at screening - Active tuberculosis at Screening - Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia (including active ventricular arrhythmia requiring medication), or unstable angina - Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study - History of malignancy other than CUP within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death - Solid organ Transplantation Prior allogeneic stem cell transplantation with follow-up 10 mg daily prednisone equivalents), or other immuno-suppressive medications within 14 days of study treatment. Inhaled or topical steroids an
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall survival (OS), defined as the time from treatment start to death from any cause - Overall response rate (ORR), defined as the proportion of subjects who exhibit a CR or PR to study treatment on two consecutive occasions = 4 weeks apart - Duration of clinical benefit (DCB), defined as the time from the first occurrence of a CR, PR or SD after treatment start until disease progression or death from any cause, whichever occurs first;Timepoint(s) of evaluation of this end point: Every 3 months tumors are staged by CT/MRI Imaging and assessed by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first. | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main purpose of the study is to determine the efficacy and safety of an immunotherapy with nivolumab plus ipilimumab in subjects with poor-prognosis CUP (non-specific subset as defined in the ESMO guidelines (Fizazi et al. 2015)) who are resistant or refractory to platinum-based first-line chemotherapy. Subjects will be stratified according to their tumor mutational burden (TMB).;Secondary Objective: To evaluate the efficacy of nivolumab plus ipilimumab in subjects with poor-prognosis CUP (non-specific subset) who are relapsed or refractory to platinum-based first-line chemotherapy;Primary end point(s): Progression-free survival (PFS), defined as the time from treatment start to the first occurrence of disease progression;Timepoint(s) of evaluation of this end point: Every 3 months tumors are staged by CT/MRI Imaging and assessed by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first. | — |
Countries
Germany
Contacts
Public ContactDepartment of Internal Medicine V
University Hospital Heidelberg
Outcome results
None listed