Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Durvalumab, Durvalumab (Cohort 1-3), Durvalumab (MEDI4736), durvalumab
Durvalumab/ Tremelimumab Combination Therapy · 1 trial · 3 indications
Serum samples were collected from the participants at the defined timepoints. Cmax was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. Cmin was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. AUC (0-14) was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. AUC (0-28) was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. Tmax was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. T½λz was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. AUC(0-14)/D was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. AUC(0-28)/D was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. Cmax/D was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. Cmax was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. Cmin was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. AUC (0-14) was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. AUC (0-28) was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. Tmax was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. T½λz was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. AUC(0-14)/D was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. AUC(0-28)/D was determined using standard non-compartmental methods.
Serum samples were collected from the participants at the defined timepoints. Cmax/D was determined using standard non-compartmental methods.
An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. SAEs were any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Some AEs and higher-level terms were considered AESI or AEPIs and this list of categories were provided by the patient safety team.
ORR as per RECIST 1.1 was defined as the percentage of participants with at least 1 investigator-assessed visit response of complete response (CR) or partial response (PR) that was subsequently confirmed on another scan not less than 4 weeks after visit observed response. CR was defined as disappearance of all target lesions (TLs), any pathological lymph nodes selected as TLs with reduction in short axis to \< 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference to baseline sum of diameters as long as criteria for PD are not met.
Duration of response was the time from the first documentation of CR/PR (which was subsequently confirmed) until the date of documented progression, or death which coincides with the progression free survival (PFS) endpoint. For participants who did not progress following a response, the DOR was censored during the PFS censoring time. It was calculated using Kaplan-Meier technique.
BOR was calculated based on the overall visit responses from each RECIST 1.1 assessment. Categorization of BOR for solid tumors were based on RECIST 1.1 using the following response categories: CR, PR, stable disease (SD), progression of disease (PD), and not evaluable (NE). CR: disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to \<10 mm. PR: 30% decrease in the sum of diameters of TLs. SD: Neither sufficient decrease in sum of diameters to qualify for PR nor sufficient increased to qualify for PD. PD: \>= 20 % increase in the sum of diameters to TLs and an increase of \>= 5 mm. NE: Only relevant if any of the TLs were not assessed or NE or had a lesion intervention at visit. Non-CR/Non-PD: Persistence of 1+ non-target lesion (s). Non-CR/non-PD was relevant to participants who did not have measurable disease at baseline.
DCR was defined as the percentage of participants who achieved a BOR of unconfirmed CR or PR, respectively, or who had SD. CR was defined as disappearance of all TLs, any pathological lymph nodes selected as TLs with reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference to baseline sum of diameters as long as criteria for PD are not met. SD: Neither sufficient decrease in sum of diameters to qualify for PR nor sufficient increased to qualify for PD.
PFS as per RECIST 1.1 was defined as the time from the date of first dose of study treatment until the date of objective disease progression or death by any cause in the absence of progression, regardless of whether the participant withdrew from study therapy or received another anti-cancer therapy prior to progression (date of PFS event or censoring - date of first dose + 1). Confidence interval was calculated using Kaplan-Meier technique.
OS was defined as the time from the date of first dose of study treatment until death due to any cause regardless of whether the patient withdraws from study treatment or received another anti-cancer therapy (i.e date of death or censoring - date of first dose + 1).
Survival rates were defined as the Kaplan-Meier estimate of OS at 12 and 24 months.
| Arm | Type | Description |
|---|---|---|
| Durvalumab / Tremelimumab Combination Therapy | EXPERIMENTAL | Part 1 (dose finding) Durvalumab + tremelimumab Combination Treatment. Durvalumab and tremelimumab are initially administered at dose level 1 and dose escalated based on results from PK modeling and tolerance to determine the RP2D. Both drugs are administered every 4 weeks as intravenous infusions. Tremelimumab is only administered with durvavalumab for 4 doses, from cycles 2-5. (sarcoma, NB and NHL) Part 2 (dose expansion phase) Durvalumab + tremelimumab Combination Treatment. Durvalumab and tremelimumab are administered at the RP2D, every 4 weeks as intravenous infusions. Tremelimumab is only administered with durvalumab for 4 doses, from cycles 1-4. Tremelimumab may be added for 4 doses at time of progressive disease. Cohorts: solid tumors, sarcomas, NHL restricted to PMBCL and ALCL subtypes) |
| Name | Type | Description |
|---|---|---|
| Durvalumab / Tremelimumab Combination Therapy | DRUG | Starting dose: durvalumab: 20mg/kg tremelimumab: 1mg/kg at cycles 2 to 5 only co-administered with durvalumab. The Recommended Phase 2 dose will be used for the dose expansion phase. |
Inclusion Criteria: * Max Age =17 years * Solid Tumors (except primary central nervous system malignant tumors): Patients must have a histopathologic confirmation of malignancy. Patients must have progressed or are refractory to standard therapies, and for whom no standard of care treatments exist ...
Durvalumab is an investigational antibody being studied for multiple cancers, including triple negative breast neoplasms, extensive-stage small cell lung cancer, invasive bladder cancer, metastatic non-small cell lung cancer, and non-small cell lung cancer. It is currently in Phase 3 clinical development and is not FDA approved.
Durvalumab is a monoclonal antibody (mab) that targets PD-L1, a protein that helps cancer cells evade the immune system. By blocking PD-L1, durvalumab aims to enhance the body's immune response against tumors. This mechanism is being evaluated across several oncology indications.
Durvalumab is developed by AstraZeneca PLC, a global biopharmaceutical company listed on the stock exchange under the ticker AZN. AstraZeneca is conducting multiple clinical trials to evaluate durvalumab as a potential treatment for various solid tumors.
Durvalumab is in Phase 3 clinical development for extensive-stage small cell lung cancer and other indications. It is an investigational drug, meaning it has not yet received FDA approval. Several Phase 3 trials are ongoing or completed, with a total of 8 clinical trials registered.
Durvalumab is being studied in 8 clinical trials, including NCT03043872 (CASPIAN), a Phase 3 trial combining durvalumab with tremelimumab and chemotherapy in untreated extensive-stage small cell lung cancer. Other trials include NCT03446547, NCT04449861, and NCT04712903, all evaluating durvalumab in lung cancer settings.
Durvalumab is also known as Durvalumab/Tremelimumab Combination Therapy, referring to its use in combination with tremelimumab. It is also referred to as Durvalumab (MEDI4736), Durvalumab + Chemotherapy, and SC durvalumab + rHu. These names describe different regimens or formulations of the same drug.