MEDI4736 for Cancer of Stomach

Phase-Based Progress Estimates
1
Effectiveness
1
Safety
Cancer of Stomach+4 More
MEDI4736 - Drug
Eligibility
18+
All Sexes
What conditions do you have?
Select

Study Summary

This trial is testing a new cancer drug combination to see if it is effective, safe, and has anti-tumor activity. The study will also look at how the drugs are metabolized and how well the combination is tolerated.

Eligible Conditions
  • Cancer of Stomach
  • Malignant Neoplasm of Stomach
  • Ovarian
  • Small Cell Lung Cancer (SCLC)
  • Breast

Treatment Effectiveness

Effectiveness Progress

1 of 3

Study Objectives

6 Primary · 13 Secondary · Reporting Duration: Olaparib Run-In treatment week 1 day 1. Olaparib Run-In treatment week 3 day 1. Each cycle = 28 days in combination of treatment. Day 1 of cycle 1; Day 15 of Cycle 1; Day 1 of Cycle 2; Day 1 of Cycle 3

Week 56
Percentage change from baseline in tumor size
Week 56
Disease control rate (DCR) [Complete response + Partial response + Stable disease (CR+PR+SD)] based on RECIST 1.1
At Screening
Tumor genetics
At baseline and upon progression
Characterize the pharmacodynamics profile of bevacizumab: Efficacy of bevacizumab in combination with olaparib and MEDI4736 compared to olaparib and MEDI4736 alone
Day 28
Bevacizumab pharmacokinetic sample
Month 3
MEDI4736 pharmacokinetic sample
PD-L1 expression in serum samples
Serum concentrations of anti-drug antibody (ADA)
Week 8
Best percentage change from baseline in tumor size
Week 8
Duration of response based on RECIST 1.1
Objective response rate (Complete response+Partial response) based on RECIST 1.1
PFS based on RECIST 1.1
Day 1
Overall Survival (OS)
Day 1
Time to study treatment discontinuation (TDT)
From screening till end of treatment
The safety and tolerability of MEDI4736 in combination with olaparib (±bevacizumab) by assessment of treatment modifications.
Day 30
The safety and tolerability of MEDI4736 in combination with olaparib (±bevacizumab) by assessment of vital signs
Day 90
The safety and tolerability of MEDI4736 in combination with olaparib (±bevacizumab) by assessment of blood samples
The safety and tolerability of MEDI4736 in combination with olaparib (±bevacizumab) by assessment of the number and grade of adverse events
The safety and tolerability of MEDI4736 in combination with olaparib (±bevacizumab) by assessment of the number and grade of immune-related adverse events
Week 1
Pharmacodynamics: whole blood for gene expression (PAXgene-RNA)
Week 1
Pharmacodynamics: circulating soluble factors in the plasma
Week 1
Pharmacodynamics: Paired tumor biopsies
Week 1
Pharmacogenetics
Week 3
Pharmacodynamics: peripheral blood mononuclear cells
Week 4
Olaparib pharamacokinetic sample
RECIST assessments performed at baseline and every 8 wks relative to baseline up to objective radiological progression, or death from any cause, whichever comes earlier, assessed until the data cut-off is reached.
ORR (CR + PR) based on RECIST 1.1, and as determined by investigator
Week 1
Pharmacodynamics: whole blood for immunophenotyping
Since Screening and untill disease progression.
Angiogenic predictive biomarkers: may include but is not limited to tumor gene expression profiling, tumor vascular morphology/microvessel density and peripheral soluble markers of angiogenesis eg, VEGF, Ang-1

Trial Safety

Side Effects for

Durvalumab
20%Anaemia
18%Asthenia
14%Constipation
14%Hypothyroidism
13%Decreased appetite
13%Fatigue
13%Weight decreased
12%Dysphagia
11%Nausea
11%Cough
11%Dyspnoea
10%Diarrhoea
8%Vomiting
8%Pyrexia
8%Rash
6%Neck pain
5%Stomatitis
5%Alanine aminotransferase increased
5%Hypertension
5%Hyponatraemia
5%Headache
4%Gamma-glutamyltransferase increased
4%Hypercalcaemia
4%Pruritus
3%Pneumonia
3%Hypomagnesaemia
3%Aspartate aminotransferase increased
3%Blood alkaline phosphatase increased
3%Insomnia
2%General physical health deterioration
2%Tumour haemorrhage
2%Pneumonia aspiration
2%Thrombocytopenia
2%Neutropenia
2%Neuropathy peripheral
2%Dermatitis acneiform
1%Subcutaneous abscess
1%Death
1%Lung infection
1%Hyperkalaemia
1%Hypocalcaemia
1%Infected neoplasm
1%Syncope
1%Lung disorder
1%Asphyxia
1%Pneumonitis
1%Respiratory failure
1%Leukopenia
1%Mucosal inflammation
1%Inappropriate antidiuretic hormone secretion
This histogram enumerates side effects from a completed 2020 Phase 3 trial (NCT02369874) in the Durvalumab ARM group. Side effects include: Anaemia with 20%, Asthenia with 18%, Constipation with 14%, Hypothyroidism with 14%, Decreased appetite with 13%.

Trial Design

3 Treatment Groups

Arm 2
1 of 3
Arm 1
1 of 3
Arm 3
1 of 3
Experimental Treatment

264 Total Participants · 3 Treatment Groups

Primary Treatment: MEDI4736 · No Placebo Group · Phase 1 & 2

Arm 2Experimental Group · 2 Interventions: Olaparib, MEDI4736 · Intervention Types: Drug, Drug
Arm 1Experimental Group · 2 Interventions: Olaparib, MEDI4736 · Intervention Types: Drug, Drug
Arm 3Experimental Group · 3 Interventions: Olaparib, MEDI4736, Bevacizumab · Intervention Types: Drug, Drug, Drug
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Olaparib
FDA approved
Durvalumab
FDA approved
Bevacizumab
FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: olaparib run-in treatment week 1 day 1. olaparib run-in treatment week 3 day 1. each cycle = 28 days in combination of treatment. day 1 of cycle 1; day 15 of cycle 1; day 1 of cycle 2; day 1 of cycle 3

Who is running the clinical trial?

AstraZenecaLead Sponsor
3,956 Previous Clinical Trials
91,808,597 Total Patients Enrolled
1 Trials studying Cancer of Stomach
1,000 Patients Enrolled for Cancer of Stomach
Iqvia Pty LtdIndustry Sponsor
90 Previous Clinical Trials
231,860 Total Patients Enrolled
Susan Domcheck, MDPrincipal InvestigatorAbramson Cancer Center, University of Pennsylvania
Susan Domchek, MDPrincipal InvestigatorAbramson Cancer Center, University of Pennsylvania
5 Previous Clinical Trials
1,800 Total Patients Enrolled

Eligibility Criteria

Age 18+ · All Participants · 10 Total Inclusion Criteria

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About The Reviewer

Michael Gill preview

Michael Gill - B. Sc.

First Published: October 26th, 2021

Last Reviewed: October 29th, 2022

Michael Gill holds a Bachelors of Science in Integrated Science and Mathematics from McMaster University. During his degree he devoted considerable time modeling the pharmacodynamics of promising drug candidates. Since then, he has leveraged this knowledge of the investigational new drug ecosystem to help his father navigate clinical trials for multiple myeloma, an experience which prompted him to co-found Power Life Sciences: a company that helps patients access randomized controlled trials.