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Adavosertib + Durvalumab for Cancer

Phase 1

Waitlist Available

Led By Manish Patel, M.D.

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologic confirmation of a solid tumour, excluding lymphoma, refractory to standard therapy or for which no standard of care regimen exists

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

Must not have

Major surgical procedures ≤28 days of beginning study treatment, or minor surgical procedures ≤7 days

Prescription or non-prescription drugs or other products known to be sensitive to CYP3A4 substrates

Timeline

Screening 3 weeks

Treatment Varies

Follow Up estimated 18 months

Awards & highlights

No Placebo-Only Group

Summary

This trial will study a new cancer drug given orally and intravenously to see if it is safe and works well against tumors.

Who is the study for?

Adults (≥18 years) with solid tumors that are unresponsive to standard treatments or have no standard care available. Participants must weigh at least 30 kg, be able to consent, and have an ECOG Performance Status of 0-1. They should not be pregnant or breastfeeding, agree to use contraception, and meet specific health criteria including blood counts and organ function tests.

What is being tested?

The trial is testing the combination of two drugs: AZD1775 (adavosertib), taken orally, and MEDI4736 (durvalumab), given intravenously. It aims to evaluate their safety, how well they're tolerated by patients' bodies, how they affect the body's handling of drugs (pharmacokinetics), immune response effects (immunogenicity), changes in disease indicators (pharmacodynamics), and initial effectiveness against advanced solid tumors.

What are the potential side effects?

Potential side effects include reactions related to drug infusion into the bloodstream; issues affecting organs due to inflammation; fatigue; gastrointestinal problems like upset stomach or diarrhea; changes in blood cell counts which can affect immunity; as well as other individual-specific reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My solid tumor does not respond to standard treatments or no treatment exists.

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I am fully active or can carry out light work.

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I weigh at least 30 kg.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't had major surgery in the last 28 days or minor surgery in the last 7 days.

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I am not taking any drugs that are known to be sensitive to CYP3A4.

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I do not have any severe or uncontrolled illnesses.

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I don't have lasting side effects from previous treatments.

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I have had cancer spread to the lining of my brain and spinal cord.

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I need treatment for fluid buildup in my abdomen.

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I have or had an autoimmune or inflammatory disorder.

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My blood pressure is not controlled by medication.

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I have an active cancer diagnosis.

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I do not have a serious active infection.

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I have had serious stomach issues causing diarrhea in the last year.

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I have had a bone marrow transplant from another person.

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I haven't taken any approved cancer treatments in the last 21 days.

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I am not allergic to any components of the study drug.

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I cannot swallow pills.

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I have interstitial lung disease.

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I have had an organ transplant and am on immunosuppressive drugs.

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I have had tuberculosis in the past.

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I am not on any other cancer treatments while on the study medication.

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I have had heart problems in the last 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ estimated 18 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~estimated 18 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and estimated 18 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

The incidence of Dose Limiting Toxicities (DLTs)

Secondary study objectives

Change from baseline in clinical chemistry, hematology, and coagulation parameters

Change from baseline in physical examination findings

Change from baseline in vital signs

+7 more

Side effects data

From 2020 Phase 2 trial • 34 Patients • NCT03012477

85%

Nausea

79%

Fatigue

74%

Vomiting

50%

Diarrhea

41%

Constipation

35%

Neutrophil count decreased

32%

Anemia

29%

Anorexia

26%

Pain

24%

Dysgeusia

24%

Headache

24%

Peripheral sensory neuropathy

21%

Dyspnea

21%

Tinnitus

18%

Cough

18%

Platelet count decreased

15%

Insomnia

15%

Urinary tract infection

12%

Back pain

12%

Dehydration

Gastrointestinal disorders - Other

Edema limbs

Dizziness

Hot flashes

Lymphedema

Abdominal pain

Aspartate aminotransferase increased

Creatinine increased

Weight gain

Confusion

Thromboembolic event

Dyspepsia

Pruritus

Rash acneiform

Skin and subcutaneous tissue disorders - Other

Alopecia

Dry skin

Weight loss

Chest wall pain

Myalgia

Neck pain

Syncope

Nervous system disorders - Other

Breast pain

Cognitive disturbance

Depression

Alanine aminotransferase increased

Alkaline phosphatase increased

Pneumonitis

Sepsis

Pain in extremity

Bruising

Pleural effusion

Sinus pain

Flatulence

Anxiety

Stomach pain

Rash maculo-papular

Cardiac arrest

Cardiac disorders - Other

Sinus tachycardia

Ear and labyrinth disorders - Other

Arthralgia

Palmar-plantar erythrodysesthesia syndrome

Hearing impaired

Endocrine disorders - Other

Hypothyroidism

Flu like symptoms

Irritability

Localized edema

Non-cardiac chest pain

Allergic reaction

Cardiac troponin T increased

Investigations - Other

Acidosis

Hypocalcemia

Hypomagnesemia

Hyponatremia

Muscle weakness upper limb

Chronic kidney disease

100%

80%

60%

40%

20%

Study treatment Arm

Cisplatin + AZD1775

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Dose Schedule DExperimental Treatment2 Interventions

In Schedule D, patients will receive MEDI4736 (durvalumab) by intravenous on Day 1, and AZD1775 (adavosertib) one time per day orally on Days 15-19, and Days 22-26 of a 28-day cycle. In Schedule D there will be a 9-day lead-in period with AZD1775 (adavosertib) being dosed on Days -9 to -5 to enable serial PK measurements prior to initiating MEDI4736 (durvalumab) on Day 1. In all dose schedules, dexamethasone will be administered as an anti-emetic on the first day of the AZD1775 (adavosertib) consecutive dosing day blocks including the lead-in portion of Schedules B, C, and D. Additional alternative dose levels and/or schedules may also be explored if emerging data suggest these would be more appropriate.

Group II: Dose Schedule CExperimental Treatment2 Interventions

In Schedule C, patients will receive MEDI4736 (durvalumab) by intravenous on Day 1, and AZD1775 (adavosertib) twice daily orally on Days 8-10, Days 15-17, and Days 22-24 of a 28-day cycle. In Schedule C there will be a 7-day AZD1775 (adavosertib) lead-in to enable serial PK measurements prior to initiating MEDI4736 (durvalumab) on Day 1. In all dose schedules, dexamethasone will be administered as an anti-emetic on the first day of the AZD1775 (adavosertib) consecutive dosing day blocks including the lead-in portion of Schedules B, C, and D. Additional alternative dose levels and/or schedules may also be explored if emerging data suggest these would be more appropriate.

Group III: Dose Schedule BExperimental Treatment2 Interventions

In Schedule B, patients will receive MEDI4736 (durvalumab) by intravenous on Day 1, and AZD1775 (adavosertib) twice daily orally on Days 15-17 and Days 22-24 of a 28-day cycle. In Schedule B there will be a 7-day AZD1775 (adavosertib) lead-in to enable serial PK measurements prior to initiating MEDI4736 on Day 1. In all dose schedules, dexamethasone will be administered as an anti-emetic on the first day of the AZD1775 (adavosertib) consecutive dosing day blocks including the lead-in portion of Schedules B, C, and D. Additional alternative dose levels and/or schedules may also be explored if emerging data suggest these would be more appropriate.

Group IV: Dose Schedule AExperimental Treatment2 Interventions

In Schedule A, patients will receive MEDI4736 (durvalumab) by intravenous on Day 1, and AZD1775 (adavosertib) twice daily orally on Days 1-5 and Days 15-19 of a 28-day cycle. In all dose schedules, dexamethasone will be administered as an anti-emetic on the first day of the AZD1775 (adavosertib).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

AZD1775

2015

Completed Phase 2

~400

MEDI4736

2016

Completed Phase 3

~5560