Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Esophageal Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Durvalumab

Oxaliplatin

Tremelimumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immunologic Factors

1. Neoadjuvant treatment Durvalumab 1120 mg IV on day (D) 1, Docetaxel 50 mg/m2 intravenously (IV) on D1, oxaliplatin 100 mg/m2 IV on D1, S-1 40 mg/m2 bid orally on D1-14, will be administered every three weeks for three cycles.
2. Surgery
3. Adjuvant treatment After 4-6 weeks from surgery, S-1 40 mg/m2 bid orally on D1-28 plus durvalumab 1120 mg on D1 and D22 will be administered every 6 weeks for 12 months as an adjuvant treatment.

Docetaxel, Oxaliplatin, S-1 and Durvalumab

1. Neoadjuvant treatment Durvalumab 1500 mg IV and tremelimumab 75 mg IV on D1 will be administered every four weeks for three cycles.
2. Surgery
3. Adjuvant treatment After 4-6 weeks from surgery, durvalumab 1500 mg on D1 will be administered every 4 weeks for 12 months as an adjuvant treatment.

Durvalumab and Tremelimumab

Min-Hee Ryu, MD, PhD

Hyung-Don Kim, MD, PhD

MD, PhD

Neoadjuvant durvalumab (MEDI4736) plus docetaxel, oxaliplatin, S-1 (DOS) followed by surgery and adjuvant durvalumab plus S-1 chemotherapy in potentially resectable MMR proficient (pMMR) gastric or gastroesophageal junction (GEJ) adenocarcinoma

* Treatment for the main treatment group (pMMR tumor)

  1. Neoadjuvant treatment Durvalumab 1120 mg IV on day (D) 1, Docetaxel 50 mg/m2 intravenously (IV) on D1, oxaliplatin 100 mg/m2 IV on D1, S-1 40 mg/m2 bid orally on D1-14, will be administered every three weeks for three cycles.
  2. Surgery
  3. Adjuvant treatment After 4-6 weeks from surgery, S-1 40 mg/m2 bid orally on D1-28 plus durvalumab 1120 mg on D1 and D22 will be administered every 6 weeks for 12 months as an adjuvant treatment.
* Treatment for the exploratory group (dMMR tumor)

  1. Neoadjuvant treatment Durvalumab 1500 mg IV and tremelimumab 75 mg IV on D1 will be administered every four weeks for three cycles.
  2. Surgery
  3. Adjuvant treatment After 4-6 weeks from surgery, durvalumab 1500 mg on D1 will be administered every 4 weeks for 12 months as an adjuvant treatment.

Trial of Neoadjuvant Durvalumab Plus Docetaxel, Oxaliplatin, S-1 Followed by Surgery and Adjuvant Durvalumab Plus S-1 Chemotherapy in Potentially Resectable MMR Proficient Gastric or Gastroesophageal Junction Adenocarcinoma

Neoadjuvant Durvalumab (MEDI4736) Plus Docetaxel, Oxaliplatin, S-1 (DOS) Followed by Surgery and Adjuvant Durvalumab Plus S-1 Chemotherapy in Potentially Resectable MMR Proficient (pMMR) Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

Asan Medical Center

Professor

Respiratory Tract (Lung and Bronchial) Diseases

Small Cell Lung Carcinoma

Carcinoma, Small Cell

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Carboplatin

Olaparib

Adavosertib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Durvalumab + tremelimumab via intravenous (IV) infusion every 4 weeks (q4w), starting on Week 0, for up to a total of 4 months (4 cycles) followed by durvalumab monotherapy via IV infusion q4w, starting on Week 16 until PD, or for other discontinuation criteria.

AZD1775 twice daily (oral) for 2.5 days from Day 1 + CBDP area under the curve 5 (Day1) (IV); every 3 weeks.

AZD1775 and carboplatin (CBPT)

AZD6738 once a day (oral) for 7 days from Day 1 + olaparib twice a day(oral) for 28 days from Day 1, every 4 weeks

AZD6738 and olaparib

Haiyi Jiang, M.D.

Study design This is a Phase II, open-label, multi-drug, multi-center, multi-arm, signal-searching study in patients with extensive-stage small-cell lung cancer (SCLC) who have refractory or resistant disease from prior platinum-based chemotherapy.

This study is modular in design, allowing evaluation of the preliminary efficacy, safety, tolerability, and immunogenicity of novel combinations of immunotherapies and/or deoxyribonucleic acid (DNA) damage repair inhibitors in patients with platinum refractory or resistant extensive-stage-disease SCLC. Patients who have progressive disease (PD) during first-line platinum-based chemotherapy (platinum refractory) or PD within 90 days after completing first-line platinum-based chemotherapy (platinum resistant) will be enrolled to the study. The primary objective of the study is to assess the preliminary efficacy of each treatment arm based on objective response rate (ORR).

This study consists of a number of arms (sub-studies), each evaluating the efficacy, safety, and tolerability of a specific agent or combination. This study was initially open with 2 arms (Arms A and B), and additional arms may open, provided there is compelling rationale for the combination and safe and tolerable doses and schedules have been determined from ongoing Phase I studies. There are 2 pre-defined arms:

A. Durvalumab + tremelimumab followed by durvalumab monotherapy B. AZD1775 + carboplatin (CBDP)

Further arm was added in amendment 3:

C. AZD6738 + olaparib Amendment #4 was updated with possibility to allow expansion of any arm, to a total of 40 eligible subjects, based on Review Committee assessment of data from the first 20 subjects (from Stage 1 and Stage 2). Currently Arm A will enroll 20 additional patients into expansion.

A Phase II, Study to Determine the Preliminary Efficacy of Novel Combinations of Treatment in Patients With Platinum Refractory Extensive-Stage Small-Cell Lung Cancer

A Phase II, Open-Label, Multi-Arm Study to Determine the Preliminary Efficacy of Novel Combinations of Treatment in Patients With Platinum Refractory Extensive-Stage Small-Cell Lung Cancer

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Overall Response Rate (ORR) using Investigator assessments according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. ORR was defined as the number (percentage) of participants with a confirmed Complete Response (CR) or confirmed Partial Response (PR) and was estimated for each treatment arm with corresponding 2-sided 95% exact confidence intervals (CIs). A confirmed response of CR/PR meant that a response of CR/PR was recorded at one visit and confirmed by repeat imaging, preferably at the next regularly scheduled imaging visit, and not less than 4 weeks after the visit when the response was first observed, with no evidence of progression between the initial and CR/PR confirmation visit.

The DoR was defined as the time from the date of first documented response (which was subsequently confirmed) CR/PR until the date of documented progression, or death in the absence of disease progression. The DoR in participants with confirmed objective response are reported.

The disease control rate (DCR) at 12 weeks was defined as the percentage of participants who had a best objective response of CR or PR in the first 13 weeks or who had demonstrated stable disease (SD) for a minimum interval of 11 weeks following the start of study treatment. The DCR was determined programmatically based on RECIST 1.1 using site Investigator data and all data up until the first progression event.

The TTR (per RECIST 1.1 as assessed by the Investigator) was defined as the time from the date of first dose until the first date of documented response.

The PFS (per RECIST 1.1 according to the Investigator's assessment) was defined as the time from the date of the 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 allocated therapy or received another anti-cancer therapy prior to progression.

The OS was defined as the time from the date of the first dose of study treatment until death due to any cause.

Time to maximum concentration for ceralasertib and olaparib are reported.

Maximum concentration for ceralasertib and olaparib are reported.

Partial area under the concentration-time curve for ceralasertib and olaparib are reported.

Area under the concentration-time curve from time zero to the last measurable concentration for Ceralasertib and Olaparib are reported.

Time to maximum concentration at steady state for Ceralasertib and Olaparib are reported.

Maximum concentration at steady state for Ceralasertib and Olaparib are reported.

Minimum concentration at steady state for Ceralasertib and Olaparib are reported.

Area under the concentration-time curve at steady state at steady state for Ceralasertib and Olaparib are reported.

Serum concentrations of Durvalumab and Tremelimumab are reported.

Plasma concentrations of Adavosertib and Carboplatin are reported.

An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. SAE is an AE that results in any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, or is a significant medical event.

AstraZeneca

Participants received durvalumab 1500 mg + tremelimumab 75 mg via intravenous (IV) infusion every 4 weeks (q4w), starting on Week 0, for up to a total of 4 months (4 cycles) followed by durvalumab monotherapy 1500 mg via IV infusion q4w, starting on Week 16 until confirmed progressive disease (PD), or other discontinuation criteria.

Arm A: Durvalumab + Tremelimumab (Original Cohort)

Participants received durvalumab 1500 mg + tremelimumab 75 mg via intravenous (IV) infusion every 4 weeks (q4w), starting on Week 0, for up to a total of 4 months (4 cycles) followed by durvalumab monotherapy 1500 mg via IV infusion q4w, starting on Week 16 until confirmed PD, or other discontinuation criteria.

Arm A: Durvalumab + Tremelimumab (Expansion Cohort)

Participants orally received adavosertib 225 mg twice daily (BID) for 2.5 days from Day 1 + carboplatin area under the curve (AUC) 5 Day 1 IV, every 3 weeks (q3w).

Arm B: Adavosertib + Carboplatin

Participants orally received ceralasertib 160 mg once daily (QD) Days 1 to 7 + olaparib 300 mg BID Days 1 to 28, q4w.

Arm C: Ceralasertib (AZD6738) + Olaparib

Total

< 50

≥ 50 to < 65

≥ 65 to < 75

≥ 75 to < 80

≥ 80

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The Full Analysis Set (FAS) included all treated participants.

Global Clinical Lead

The FAS included all treated participants.

Number of Participants With Overall Response

Duration of Response (DoR)

Percentage of Participants With Disease Control at 12 Weeks

Time to Response (TTR)

Progression Free Survival (PFS)

Overall Survival (OS)

Ceralasertib (AZD6738)

Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study treatment and had post-dose data available, excluding those who had a deviation considered by the sponsor to have a potential impact on the interpretation of the pharmacokinetic analyses.

Time to Maximum Concentration (Tmax)

Maximum Concentration (Cmax)

Cycle 1, Day 1

Cycle 1, Day 7

Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study treatment and had post-dose data available, excluding those who had a deviation considered by the sponsor to have a potential impact on the interpretation of the pharmacokinetic analyses. Here, number analyzed in each row signifies only participants with available data that were analyzed for that specified time point.

Partial Area Under the Concentration-time Curve (AUC0-6)

Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t)

Time to Maximum Concentration at Steady State (Tmax,ss)

Maximum Concentration at Steady State (Cmax,ss)

Minimum Concentration at Steady State (Cmin,ss)

Area Under the Concentration-time Curve at Steady State (AUCss)

Apparent Clearance of Drug at Steady State at Steady State (CLss/F)

Durvalumab: Cycle 1 Day 1 (Post-dose)

Durvalumab: Cycle 2 Day 1 (Pre-dose)

Durvalumab: Cycle 5 Day 1 (Pre-dose)

Tremelimumab: Cycle 1 Day 1 (Post-dose)

Tremelimumab: Cycle 2 Day 1 (Pre-dose)

Tremelimumab: Cycle 5 Day 1 (No dose)

Tremelimumab: Cycle 7 Day 1 (No dose)

Serum Concentrations of Durvalumab and Tremelimumab

Adavosertib: Cycle 1 Day 3 (Pre-dose)

Adavosertib: Cycle 1 Day 3 (Post-dose)

Adavosertib: Cycle 3 Day 3 (Pre-dose)

Adavosertib: Cycle 3 Day 3 (Post-dose)

Carboplatin: Cycle 1 Day 1 (Post-dose)

Plasma Concentrations of Adavosertib and Carboplatin

Any AE

Any AE causally related to any study treatment

Any AE with outcome = death

Any SAE

Any AE leading to discontinuation of any study treatment

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Overall Study

Symptoms and General Pathology

Recurrence

Immunomodulating Agents

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.

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

Neoplasm Metastasis

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Processes

Hematinics

Liver Extracts

Six patients will be enrolled in cohorts of three to be administered Y-90, SBRT, and Druvalumab.

Six patients will be enrolled in cohorts of three to be administered Y-90, SBRT, and Druvalumab + Tremelimumab.

Durvalumab will be dosed at 1500 mg fixed dosing every 4 weeks and continued at this interval until progression or dose-limiting toxicity.

Durvalumab will be dosed at 1500 mg fixed dosing every 4 weeks and continued at this interval until progression or dose-limiting toxicity. Tremelimumab will be dosed at 75 mg every 4 weeks (same day as durvalumab infusion) for a maximum of 4 doses.

Yttrium-90 microsphere therapy consists of resin beads loaded with Yttrium, a pure beta emitter with a 64.2 hour half-life. Radioembolization will be performed as standard of care therapy per current NCCN guidelines.

Y-90 Selective Internal Radiation Therapy (SIRT)

High-dose hypofractionated conformal external beam radiation therapy that is considered a standard of care. SBRT will also be considered for metastases that are persistent and/or progressive after Y-90 based on MR imaging and pathology from tissue biopsies.

Stereotactic Body Radiation Therapy (SBRT)

Karyn Goodman, MD

This study is evaluating the combination of Y-90 radioembolization followed by SBRT with the immunotherapy drugs, durvalumab and tremelimumab, to improve disease control of liver metastases for patients with microsatellite stable colorectal cancer.

The first 6 patients will receive durvalumab alone with Y-90 and SBRT followed by 4 months of durvalumab. The next 6 patients will received durvalumab with Y-90 and SBRT followed by 4 months of durvalumab + tremelimumab.Durvalumab will be dosed at 1500 mg fixed dosing every 4 weeks and continued at this interval until progression or dose-limiting toxicity. There will be no dose escalation. For patients who will receive both Durvalumab and Tremelimumab, the Tremelimumab will be dosed at 75 mg every 4 weeks (same day as durvalumab infusion) for a maximum of 4 doses. There will be no dose escalation.

Immunotherapy Combined With Y-90 and SBRT for Colorectal Liver Metastases

Phase I Study of Dual Immune Checkpoint Blockade (Anti-PD-L1 (Durvalumab) (MEDI4736) and Anti-CTLA4 (Tremelimumab) Plus Yttrium-90 (Y-90) Radioembolization & Stereotactic Body Radiation Therapy (SBRT) in Refractory Metastatic MSS (Microsatellite Stable) Colorectal Cancer With Liver Metastases

Adverse events related to Y-90, SBRT, and durvalumab plus tremelimumab will be summarized by dose and severity as assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.

Defined as the rate of \>Grade 3 treatment-related adverse events during treatment or within 3 months of treatment completion.

The determination of antitumor activity will be based on objective response assessments as defined by RECIST version 1.1 and immune RECIST.

Measure of overall survival rate by examining the incidence of death over a two year period.

Measured by the percentage of viable tumor throughout and post treatment

University of Colorado, Denver

Sarcoma

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Cycles/courses 1-3:

Durvalumab 1.5g q4wks Tremelimumab 75 mg q4wks

Cycles/courses ≥4:

Durvalumab 1.5g q4wks Tremelimumab 75 mg q12wks

Viktor Grünwald, Dr.

The objective of the trial is to assess the efficacy of Durvalumab and Tremelimumab in comparison to doxorubicin in treatment-naïve Soft tissue sarcoma patients

Treatment Arm A: Combination of Durvalumab and Tremelimumab Treatment Arm B: Doxorubicin

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of Neoadjuvant Durvalumab Plus Docetaxel, Oxaliplatin, S-1 Followed by Surgery and Adjuvant Durvalumab Plus S-1 Chemotherapy in Potentially Resectable MMR Proficient Gastric or Gastroesophageal Junction Adenocarcinoma	NCT04221555	Resectable Gast...	Docetaxel, Oxal... Durvalumab and ...	19 Years -	Asan Medical Center
A Phase II, Study to Determine the Preliminary Efficacy of Novel Combinations of Treatment in Patients With Platinum Refractory Extensive-Stage Small-Cell Lung Cancer	NCT02937818	Platinum Refrac...	Durvalumab and ... AZD1775 and car... AZD6738 and ola...	18 Years - 130 Years	AstraZeneca
Trial of Neoadjuvant Durvalumab Plus Docetaxel, Oxaliplatin, S-1 Followed by Surgery and Adjuvant Durvalumab Plus S-1 Chemotherapy in Potentially Resectable MMR Proficient Gastric or Gastroesophageal Junction Adenocarcinoma	NCT04221555	Resectable Gast...	Docetaxel, Oxal... Durvalumab and ...	19 Years -	Asan Medical Center
Durvalumab and Tremelimumab Combination in Somatically Hypermutated Recurrent Solid Tumors	NCT03911557	Tumor, Solid	Durvalumab and ...	18 Years -	University of Kentucky
Immunotherapy Combined With Y-90 and SBRT for Colorectal Liver Metastases	NCT03802747	Colorectal Canc...	Durvalumab Durvalumab and ... Y-90 Selective ... Stereotactic Bo...	18 Years -	University of Colorado, Denver
Durvalumab and Tremelimumab Compared to Doxorubicin in Patients With Advanced or Metastatic Soft Tissue Sarcoma	NCT03317457	Metastatic Adul... Recurrent Adult...	Durvalumab and ... Doxorubicin	18 Years -	AIO-Studien-gGmbH

Spots Global Cancer Trial Database for durvalumab and tremelimumab