Symptoms and General Pathology

All Conditions

Recurrence

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Durvalumab

Tremelimumab

Antineoplastic Agents, Immunological

Patients with recurrent or refractory disease in solid tumors naïve to anti-PD-1/PD-L1 or anti-CTLA-4 immunotherapy and have moderate to high tumor mutational burden (TMB)

Durvalumab 1500mg + tremelimumab 75mg via IV infusion Q4W, starting on Week 1, for up to a maximum of 4 doses/cycles followed by durvalumab monotherapy 1500 mg via IV infusion Q4W, starting 4 weeks after the last infusion of the combination, for up to a maximum of 2 years of total therapy.

Durvalumab and Tremelimumab

John Villano, MD

This study will examine whether patients with relapsed/refractory solid tumors harboring evidence of somatic hypermutation (intermediate versus high tumor mutational burden) will exhibit improvement in disease progression-free survival with dual Tremelimumab and Durvalumab treatment.

This study is phase II basket trial to evaluate the benefit of immunotherapy (Durvalumab and Tremelimumab combination) in treatment of relapse/refractory solid tumor patients whose tumors express a high tumor mutational burden (TMB high \>20 mutations/MB) or moderate tumor mutational burden (10-20 mutations/MB) as based on next generation sequencing (NGS). The primary endpoint of the study is the TTP (time-to-progression) ratio or growth modulation index (GMI) which is defined for individual patients as the ratio of their TTP on the current therapy to their TTP on the most recent previous therapy.

Durvalumab and Tremelimumab Combination in Somatically Hypermutated Recurrent Solid Tumors

Phase 2 Investigation of MEDI4736 (Durvalumab) and Tremelimumab Combination in Somatically Hypermutated Recurrent Solid Tumors

The TTP (time-to-progression) ratio is defined for individual patients as the ratio of their TTP on the current therapy to their TTP on the most recent previous therapy

time to progression or death as measured from start of treatment

John L. Villano, MD, PhD

Professor

Anti-Infective Agents

Everolimus

Atezolizumab

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Immune Checkpoint Inhibitors

Cobimetinib, 60mg po daily. 28 day cycle; day 1-21 60mg daily, day 22-28 rest period.

Cobimetinib

Hannah Karlsson, PhD

Lars Ny, MD, PhD

Ana Carneiro, MD, PhD

Joakim Crona, MD, PhD

Peter Nygren, MD, PhD

Peter Asplund, BSc

This is a prospective, open-label, non-randomized combined basket- and umbrella trial divided in two parts; a limited feasibility-oriented part 1 including 154 patients and 3 treatment cohorts and part 2 that will include an expanded cohort of patients and treatment cohorts. The overall aims of the study are to test the feasibility, safety and efficacy of comprehensive genomic profiling on fresh tumor biopsies as a basis for treatment decision making and to compare two different sequencing, bioinformatics and decision-making platforms (part 1). Also to evaluate the efficacy and safety of off-label treatment with cancer drugs in patients selected based on genomic biomarker matching.

This is a prospective, open-label, non-randomized combined basket- and umbrella trial divided in two parts; a limited feasibility-oriented part 1 including 154 patients and 3 treatment cohorts (mutation/drug) and part 2 that will include an expanded cohort of patients and treatment cohorts. The overall aims of the study are to test the feasibility, safety and efficacy of comprehensive genomic profiling on fresh tumor biopsies as a basis for treatment decision making and to compare two different sequencing, bioinformatics and decision-making platforms (part 1). Also to evaluate the efficacy and safety of off-label treatment with cancer drugs in patients selected based on genomic biomarker matching.

Combined umbrella and basket trial. Treatment selection based on mutation status.

A MolEcularly Guided Anti-Cancer Drug Off-Label Trial

MEGALiT - a Multicenter, Basket and Umbrella Explorative Trial on the Efficacy and Safety of Molecular Profile Selected Commercially Available Targeted Anti-cancer Drugs in Patients With Advanced Cancers Progressive on Standard Therapy

The proportion of patients that have a best overall response of complete response (CR), partial response (PR) or stable disease ≥16 weeks, as assessed by RECIST 1.1 criteria

Time to and duration of tumor response and stable disease, progression free survival, overall survival and progression free survival on study drug compared with that on the treatment preceding study drug treatment.

Incidence and severity of study drug related adverse events (AEs) and serious adverse events (SAEs). Include recording of changes in laboratory values, vital signs (body temperature, blood pressure, heart rate, respiratory rate), and assessment of physical, dermatological examinations graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

Safety of core needle biopsy in advanced cancer scored according to NCI Common Terminology Criteria for Adverse Events 4.03 as grade 3 - 4 adverse event related to the procedure.

Actionable target concordance between genomic analysis results from the Foundation Medicine platform F1CDx with that from the similar local analysis.

Overall survival of patients starting treatment in accordance with 1 of the 4 groups of genomic markers compared with patients included in the trial but that do not start such treatment due to lack of appropriate marker.

Feasibility of comprehensive genomic testing of fresh tumor tissue for treatment decision, defined as the proportion of patients included with actionable genomic analysis within 4 weeks from inclusion

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Durvalumab and Tremelimumab Combination in Somatically Hypermutated Recurrent Solid Tumors	NCT03911557	Tumor, Solid	Durvalumab and ...	18 Years -	University of Kentucky
A MolEcularly Guided Anti-Cancer Drug Off-Label Trial	NCT04185831	Solid Tumor	Atezolizumab Everolimus Cobimetinib	18 Years -	Uppsala University Hospital

Spots Global Cancer Trial Database for mutational burden