AzTrials
AzTrials

Advanced Solid MalignanciesPhase 1NCT02740985

A Phase 1 Clinical Study of AZD4635 in Patients With Advanced Solid Malignancies

A Phase 1 study testing AZD4635, Durvalumab and Abiraterone Acetate in people with Advanced Solid Malignancies and Non-Small Cell Lung Cancer (NSCLC), run by AstraZeneca at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a Phase 1, open-label, multicenter study of continuous oral dosing of AZD4635 administered to patients with advanced solid malignancies. Dosing will be escalated until a maximum-tolerated dose (MTD) is determined in patients. The MTD will be defined by dose-limiting toxicity. Read more about this study

Who is it for?
Ages 18 to 130 years
What is being tested?
AZD4635, Durvalumab and Abiraterone Acetate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
313 participants
Where
17 sitesUnited States
Study dates
17 Jun 2016to 31 Mar 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 130 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient must consent to the study and provide a signed and dated written informed consent document prior to any study-specific procedures, sampling, or analyses.
  • Age ≥18 years
  • Weight ≥77 lbs (35 kg)
  • Availability of an archival tumor tissue sample. If archival tumor tissue is not available, then tissue from a fresh biopsy can be used.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 w/ no clinical deterioration over the prior 2 weeks (wks) and likely able to complete at least 9 wks of treatment.
  • Normotensive or well controlled blood pressure (systolic <150 and diastolic <90) w/ or without current anti-hypertensive treatment. If there is a diagnosis or history of hypertension, patient must have adequately controlled BP on antihypertensive medications as demonstrated by 2 BP measurements taken in the clinical setting by a medical professional within 1 week (wk) prior to enrollment. Patients on anti-hypertensive medication must be willing and able to check and record twice daily BP readings for a minimum of 3 wks.
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  • Females should be using adequate contraceptive measures from the time of screening until 3 months after study discontinuation, should not be breast feeding and must have negative pregnancy test prior to the start of dosing, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
  • Post-menopausal: defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
  • Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation.
  • Women under 50 years-of-age will be considered postmenopausal if they have been amenorrheic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone and luteinizing hormone levels in the postmenopausal range for the institution.
  • Male patients should be willing to use barrier contraception for the duration of the study and for 3 months after treatment discontinuation.
  • Ability to swallow and retain oral medication.
  • Additional Inclusion Criteria for Phase 1a Arms AA and EA
  • 1. Patients in Arms AA and EA must have metastatic prostate cancer w/ histological or cytological confirmation. Note: Patient may have bone only metastatic disease.
  • Patients must be castrate-resistant (i.e. developed progression of metastases following surgical castration or during medical androgen ablation therapy). (Patients receiving medical castration therapy w/ gonadotropin-releasing hormone analogues should continue this treatment during this study.)
  • Patients must have received prior treatment w/ at least one of the hormonal agents (abiraterone acetate, enzalutamide or apalutamide). Patients who received prior apalutamide will be allocated to abiraterone acetate (Arm AA). Note: Prior chemotherapy is allowed but not required.
  • Patients must have evidence of disease progression.
  • Additional Inclusion Criteria for Phase 1a Arm CA
  • Patients in Arm CA must have a histologically/cytologically confirmed advanced solid tumor malignancy that has received and progressed on standard-of-care therapy(ies).
  • Additional Inclusion Criteria for Phase 1a Arms CB and CC
  • Patients in Arms CB and CC may have metastatic prostate cancer w/ histological or cytological confirmation:
  • Patient must be castrate-resistant (i.e., developed progression of metastases following surgical castration or during medical androgen ablation therapy). Patients receiving medical castration therapy with gonadotropin-releasing hormone analogues should continue this treatment during this study. Note: Patient with prostate cancer may have bone-only metastatic disease.
  • Patient must have-evidence of disease progression. Or
  • Patients in Cohort CB must have a histologically/cytologically confirmed advanced solid tumor malignancy that has received and progressed on standard-of-care therapy(ies).
  • Or • Patients in Cohort CC should have a histologically/cytologically confirmed advanced solid tumor malignancy suitable for treatment with docetaxel.
  • Additional Inclusion Criteria for Phase 1b
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  • Patients must have disease that is suitable for repeated measurement, either: a) at least one lesion that can be accurately assessed at baseline by computed tomography (CT), magnetic resonance imaging (MRI) or X-ray, that is suitable for repeated measurement (RECIST v1.1), or b) for patients with mCRPC (Arms I and J), patients must have measurable PSA above normal limits (per local ranges).
  • A minimum of 10 patients with mCRPC, CRC and 'Other' tumors will be required to have a site of disease that is safely accessible for biopsy (paired) upon enrollment. Accessible lesions are defined as those which are biopsiable (at screening) and amenable to repeat biopsy (after 2 wks of monotherapy), unless clinically contraindicated. In the case that the second sample is not taken, the patient will remain in the study and there will be no penalty or loss of benefit to the patient and they will not be excluded from other aspects of the study. The tumor-specific cohorts will be closely monitored to ensure the desired number of biopsiable patients are enrolled. The requirement for biopsies must be made clear to each patient at the time of initial approach by the Investigator.
  • For post immunotherapy patients with NSCLC (Arms F and G) all of the following must apply:
  • Patients must have advanced or metastatic NSCLC w/ histological or cytological confirmation. Patients with known EGFR-activating mutations or ALK rearrangements are excluded.
  • Patient must have previously received one (but no more than one) line of previous therapy w/ an anti-PD-1/PD-L1 mAb therapy either alone or in combination and have either progressed or responded and then stopped responding.
  • For other post-immunotherapy patients (Arm H) all of the following must apply:
  • Patients must have an immune checkpoint resistant malignancy (for example, RCC, head and neck carcinoma, or MSI high cancers which have approved settings for anti-PD1 treatment), confirmed histologically or cytologically.
  • Patients must have previously received at least one line (and not more than 2 lines) of previous therapy w/ an anti-PD-1/PD-L1 mAb therapy, either alone or in combination and have either progressed or responded and then stopped responding.
  • For immune checkpoint naïve CRPC patients (Arms I and J) all of the following must apply:
  • Patients must have metastatic prostate cancer w/ histological or cytological confirmation.
  • Patients must be castrate-resistant (i.e., developed progression of metastases following surgical castration or during medical androgen ablation therapy). Patients receiving medical castration therapy w/ gonadotropin-releasing hormone analog should continue this treatment during this study.
  • Patients must have previously received and progressed on standard-of-care therapy(ies).
  • Approximately 60 out of 80 patients w/ mCRPC enrolled must have measurable disease (approximately 30 out of 40 patients in each of the mCRPC arms I and J) that is suitable for repeated measurement (RECIST v1.1). Enrollment will be monitored to ensure the required number of patients with measurable disease enter the study.
  • For immune checkpoint naïve patients (Arms K and KD) all of the following must apply:
  • Patients must have immune checkpoint naïve histologically/cytologically confirmed advanced or metastatic colorectal carcinoma (CRC).
  • Patients must have previously received and progressed on at least 1 prior chemotherapy regimen.
  • For other immune checkpoint naïve tumor patients (Arm L) all of the following must apply:
  • Patients w/ other immune checkpoint naïve histologically/ cytologically confirmed advanced solid tumor type that has received and progressed on standard-of-care therapy(ies).

Who cannot join

  • Treatment with any of the following:
  • Nitrosourea or mitomycin C within 6 wks of the first dose.
  • Any systemic anti-cancer chemotherapy, small molecule, biologic, or hormonal agent from a previous treatment regimen or clinical study within 21 days or 5 half-lives (whichever is shorter). At least 7 days must have elapsed between the last dose of such agent and the first dose of study drug. EXCEPTION: Androgen-deprivation therapy is recommended for patients w/ prostate cancer.
  • Enrollment into another therapeutic clinical trial. EXCEPTION: Patients are allowed to participate in investigational imaging or non-therapeutic studies.
  • Patient has had Rx or non-Rx drugs or other products known to be sensitive BCRP or OAT1 substrates or to be potent inhibitors/inducers of CYP1A2, which cannot be discontinued 2 wks prior to Day 1 of dosing and withheld throughout the study until 2 wks after the last dose of AZD4635.
  • Herbal preparations/medications are not allowed throughout the study, including but not limited to St. John's Wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone, yohimbe, saw palmetto, and ginseng. Patients should stop using these herbal medications 7 days prior to the first dose of AZD4635.
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  • Patient may not be assigned to abiraterone acetate arm (Arm AA) if co-administration of a strong CYP3A4 or a CYP2D6 substrate with a narrow therapeutic index is required during study treatment.
  • Patient may not be assigned to an enzalutamide arm (Arm EA) if co-administration of strong CYP2C8 inhibitor, strong or moderate CYP3A4 or CYP2C8 inducer, or CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index is required during study treatment.
  • Ongoing treatment w/ Coumadin.
  • Concomitant medications w/ another A1R antagonist that would increase risk of seizure (e.g., theophylline or aminophylline).
  • AZD4635 in the present study (i.e., dosing w/ AZD4635 previously initiated in a different arm in this study), or prior therapy w/ AZD4635 or any other A2AR antagonist.
  • Ongoing corticosteroid use. NOTE: mCRPC patients assigned to an arm with abiraterone acetate (Arm AA) should take prednisone as prescribed for glucocorticoid replacement therapy and patients assigned to the docetaxel arm (Arm CC) should take prophylactic dexamethasone (or equivalent) to prevent severe hypersensitivity reactions.
  • Major surgery (excluding placement of vascular access) within 4 wks of the first dose of study treatment.
  • Radiotherapy w/ a wide field of radiation within 4 wks or radiotherapy w/ a limited field of radiation for palliation within 2 wks of the first dose of study treatment.
  • Patient w/ prior history of myocardial infarction, transient ischemic attack, or stroke within 3 months prior to the scheduled first dose of oleclumab treatment (Arm CB).
  • With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment must be discussed with the Medical Monitor.
  • History of seizures, central nervous system tumors or CNS metastasis. Due to the incidence of silent CNS metastases in patients with advanced NSCLC, such patients must undergo mandatory screening with brain MRI or CT scan to determine eligibility.
  • Significant mental illness in the 4-wk period preceding drug administration.
  • As judged by the investigator, any evidence of severe or uncontrolled systemic disease, including uncontrolled hypertension, active bleeding diatheses, or active infection, including hepatitis B, hepatitis C, and human immunodeficiency virus. Screening for chronic conditions is not required.
  • History or presence of another primary invasive malignancy except for:
  • Malignancy treated w/ curative intent and w/ no known active disease ≥2 years before the first dose of study drug and of low potential risk for recurrence.
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  • Adequately treated carcinoma in situ without evidence of disease.
  • Localized non-invasive primary under surveillance.
  • Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTcF) >470 msec obtained from 3 ECGs.
  • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle branch block, third degree heart block.
  • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication known to prolong the QT interval. Patients receiving a medication(s) known to prolong QT internval may be discussed w/ the Medical Monitor or Sponsor for study approval.
  • Ejection fraction <55% or less than the lower limit of normal of the institutional standard.
  • Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
  • Absolute neutrophil count <1.5 x 10^9/L
  • Platelet count <100 x 10^9/L
  • Hemoglobin <90 g/L
  • ALT and/or AST >2.5 x the upper limit of normal (ULN) if no demonstrable liver metastases or >5 x ULN in the presence of liver metastases
  • Total bilirubin >1.5 x ULN
  • Creatinine >1.5 x ULN concurrent with creatinine clearance <50 mL/min
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, or previous significant bowel resection that would preclude adequate absorption of AZD4635.
  • Any patient w/ open oral ulceration(s) should avoid dosing with AZD4635 oral suspension.
  • Patients w/ severe hepatic impairment (Child-Pugh Class C) are not permitted to enroll in the mCRPC plus hormone arms containing abiraterone acetate.
  • Organ transplant that requires the use of immunosuppressive treatment.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g. colitis, Crohn's disease], diverticulitis, celiac disease, systemic lupus erythematous, Wegner's syndrome, myasthenia gravis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis, autoimmune pneumonitis, autoimmune nephritis or nephropathy, etc.) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
  • Vitiligo or alopecia.
  • Hypothyroidism (e.g., following Hashimoto's disease) stable on hormone replacement.
  • Psoriasis or eczema not requiring systemic treatment.
  • Patients w/ prior ≥Grade 3, serious, or life threatening immune-mediated reactions following prior anti-PD-1 or other immune-oncology therapies.
  • History of hypersensitivity to AZD4635 or drugs w/ a similar chemical structure or class to AZD4635.
  • Judgment by the Investigator or the Medical Monitor that the patient should not participate in the study if the patient is unlikely to comply w/ study procedures, restrictions, and/or requirements.

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • Research Site

    Chattanooga, Tennessee, 37404

  • Research Site

    Daytona Beach, Florida, 32117

  • Research Site

    Decatur, Illinois, 62526

  • Research Site

    Denver, Colorado, 80218

  • Research Site

    Durham, North Carolina, 27710

  • Research Site

    Fayetteville, Arkansas, 72703

  • Research Site

    Fresno, California, 93720

  • Research Site

    Las Vegas, Nevada, 89119

  • Research Site

    Lecanto, Florida, 34461

  • Research Site

    Myrtle Beach, South Carolina, 29572

  • Research Site

    Nashville, Tennessee, 37203

  • Research Site

    New Haven, Connecticut, 06519

  • Research Site

    New York, New York, 10032

  • Research Site

    North Port, Florida, 34288

  • Research Site

    Oklahoma City, Oklahoma, 73104

  • Research Site

    Philadelphia, Pennsylvania, 19107

  • Research Site

    Sarasota, Florida, 34232

Other trials in United States

About this study

Official title: A Phase 1, Open-Label, Multicenter Study to Assess Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-Tumor Activity of Ascending Doses of AZD4635 Both as Monotherapy and in Combination in Patients With Advanced Solid Malignancies

This is a Phase 1, open-label, multicenter study of continuous oral dosing of AZD4635 administered to patients with advanced solid malignancies. Dosing will be escalated until a maximum-tolerated dose (MTD) is determined in patients. The MTD will be defined by dose-limiting toxicity. The study design allows an escalation of dose with intensive safety monitoring to ensure the safety of the patients. Expansion cohorts will further assess safety and preliminary anti-tumor activity in a variety of advanced solid tumor malignancies. Other dosing schedules and/or combinations may be evaluated based on the emerging PK and safety data.

The primary objectives of this study are to:

  • Investigate the safety and tolerability of AZD4635 monotherapy when given orally (PO) to patients with advanced solid malignancies.
  • Investigate the safety, tolerability, and pharmacokinetics (PK) of AZD4635 monotherapy capsule formulation when given to patients with advanced solid malignancies.
  • Investigate the safety and tolerability of AZD4635 PO when given in combination with durvalumab, durvalumab plus oleclumab, or docetaxel to patients with advanced solid malignancies and to investigate the safety and tolerability of AZD4635 in combination with abiraterone acetate or enzalutamide in patients with mCRPC.
  • Define the maximum-tolerated dose (MTD) of AZD4635 in combination with durvalumab.
  • Define the recommended Phase 2 dose (RP2D) of AZD4635 in combination with abiraterone acetate or enzalutamide.
  • Determine the safety, tolerability, and immune effects of AZD4635 when administered in combination with durvalumab to patients with non-small cell lung cancer (NSCLC) who have previously received immunotherapy (Phase 1b portion).
  • Investigate the safety and tolerability of AZD4635 capsule formulation in combination with durvalumab and oleclumab when given to patients with mCRPC or advanced solid tumor malignancy.
  • Define the RP2D of AZD4635 capsule formulation in combination with durvalumab and oleclumab when given to patients with mCRPC or advanced solid tumor malignancy.
  • Investigate the safety and tolerability of AZD4635 capsule formulation in combination with docetaxel when given to patients with mCRPC or advanced solid tumor malignancy.
  • Define the RP2D of AZD4635 capsule formulation in combination with docetaxel when given to patients with mCRPC or advanced solid tumor malignancy.
Read the detailed description

The study will be conducted in two segments. The first segment of the study, designated Phase 1a, will be a dose escalation design in order to assess the safety, tolerability, pharmacokinetics (PK), and preliminary anti-tumor activity of ascending doses of AZD4635 as monotherapy, in combination with durvalumab or durvalumab plus oleclumab, in combination with docetaxel, and in combination with either abiraterone acetate or with enzalutamide.

A capsule formulation of AZD4635 will be evaluated in 3 arms (arms CA, CB, and CC). An oral nanoparticle suspension in water constituted extemporaneously by the patient will be administered in all other treatment arms. Most patients who started therapy with the nanoparticle suspension will transition to the capsule dosage form depending on the arm they are assigned to and emerging data. Active patients in arms C, D, E, F, G, H, I, J, K, KD, and L should be offered the option to transition to the capsule formulation at the discretion of the Investigator in discussion with the Medical Monitor. Patients in study arms AA and AE receiving AZD4635 as the nanoparticle suspension should change over to the capsule formulation as soon as possible at the discretion of the Investigator.

The dose escalation arms are described as follows:

  • Arms A, B, and C (dose escalation of AZD4635 monotherapy).
  • Arms CA, CB, and CC. In arm CA, the safety, tolerability and PK of the capsule formulation will be assessed in approximately 6 patients with advanced solid malignancies to ensure at least 5 patients have evaluable pharmacokinetic sampling. An additional 12 patients will be enrolled in this arm. Arm CB will assess the safety and tolerability and determine the RP2D of the AZD4635 capsule plus durvalumab and oleclumab in approximately 12 patients. Arm CC will assess the safety, tolerability and determine the RP2D of AZD4635 capsule plus docetaxel in approximately 12 patients .
  • Arms D and E [dose escalation of AZD4635 in combination with durvalumab anti-programmed death-ligand 1 (PD-L1)].

Arms A through E enrolled 38 patients in Phase 1a in order to establish the Recommended Phase 2 Dose (RP2D) of the nanoparticle suspension formulation of AZD4635 as a single agent or in combination with durvalumab.

● Arms EA and AA. Arms EA and AA [dose escalation of AZD4635 in combination with either abiraterone acetate plus prednisone or enzalutamide in patients with metastatic castrate-resistant prostate cancer (mRCPC)]. The AZD4635 plus hormonal therapy cohorts will enroll concurrently. Patients who previously received abiraterone acetate, enzalutamide, or apalutamide as part of their prior treatments for mCRPC may be enrolled to the enzalutamide plus AZD4635 arm (Cohort EA) or the abiraterone acetate plus AZD4635 arm (Cohort AA) at the discretion of the Investigator. Approximately 24 to 48 patients with mCRPC will be treated in the AZD4635 plus hormonal therapy arms in order to establish the RP2D.

In Phase 1a approximately 90-132 patients will be treated with AZD4635 as a single agent or in combination with durvalumab, durvalumab plus oleclumab, docetaxel, abiraterone acetate or enzalutamide.

The second segment of the study, designated Phase 1b, will further assess the safety and preliminary activity in the expansion arms described below.

  • Arm F - AZD4635 in combination with durvalumab. Post-immunotherapy non-small cell lung cancer (NSCLC). [15 patients]
  • Arm G - AZD4635 monotherapy. Post-immunotherapy NSCLC. [15 patients]
  • Arm H - AZD4635 monotherapy. Immune checkpoint resistant malignancies, previously treated with approved immunotherapy and progressed or responded and then stopped responding (e.g. renal cell carcinoma, head and neck carcinoma, or MSI high cancers which have approved settings for anti-PD-1 treatment).[20 patients]
  • Arm I - AZD4635 in combination with durvalumab. Immune checkpoint naïve mCRPC.[40 patients]
  • Arm J - AZD4635 monotherapy. Immune checkpoint naïve CRPC. [40 patients]
  • Arm K - AZD4635 monotherapy. Immune checkpoint naïve colorectal carcinoma (CRC). CRC, excluding MSI high, which has not been treated with immune checkpoint inhibitors. [20 patients]
  • Arm KD - AZD4635 in combination with durvalumab. Immune checkpoint naïve CRC. CRC, excluding MSI high, which has not been treated with immune checkpoint inhibitors. [20 patients]
  • Arm L - AZD4635 monotherapy. Other solid tumours immune checkpoint naïve. Relapsed/refractory tumors which have not been treated with immune checkpoint inhibitors. [20 patients]

Patients will be randomly assigned between open-label arms with AZD4635 monotherapy and AZD4635 combined with durvalumab in NSCLC (Arms F/G) and mCRPC (Arms I/J) in order to minimize bias.

Patients with CRC, excluding MSI high, will be enrolled to AZD4635 monotherapy (Arm K) and AZD4635 combined with durvalumab (Arm KD) in patients with CRC.

Some arms will have a mandatory biopsy subgroup to ensure sufficient tissue is collected to assess the mechanism of action in tissue without excluding patients with nonbiopsiable disease. Biopsies are optional in all other arms.

Being tested
AZD4635, Durvalumab, Abiraterone Acetate, Enzalutamide, Oleclumab
Keywords
AZD4635, durvalumab, oleclumab, docetaxel, non-small cell lung cancer, advanced solid malignancies, prostate cancer, colorectal cancer, abiraterone acetate, enzalutamide
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD4635Drug

    AZD4635 will be administered orally as a nanosuspension or capsule on a continuous schedule in Arms A, B, C, D, E, F, G, H, I, J, K, KD, L, AA, and EA. The AZD4635 nanoparticle drug product will be constituted extemporaneously as an oral suspension by the patient immediately prior to dosing. In Arms CA, CB, and CC AZD4635 will be administered as 75 mg or 50 mg capsules. Additionally, in Arm CA, AZD4635 will also be administered at 150 mg and 200 mg, or a lower dose of 125 mg or 100 mg may be given.

  • DurvalumabDrug

    Also called MEDI4736

    Durvalumab will be administered by intravenous infusion once every 4 weeks. Durvalumab should be reconstituted using aseptic techniques with sterile water for injection. The reconstituted solution will be diluted with 0.9% (w/v) saline prior to IV infusion.

  • Abiraterone AcetateDrug

    Also called Zytiga

    Abiraterone acetate 1000 mg PO QD will be given with prednisone BID. The patient must receive abiraterone/prednisone according to the prescribing information during the DLT assessment period, Cycle 1 and Cycle 2. After Cycle 2 necessary abiraterone/ prednisone dose modifications may follow institutional standard practice.

    Abiraterone acetate is supplied in 250 mg tablets.

  • EnzalutamideDrug

    Also called Xtandi

    Enzalutamide 160 mg PO QD will be dosed per the approved package insert. The patient must receive enzalutamide according to the prescribing information during the DLT assessment period, Cycle 1 and Cycle 2. After Cycle 2 necessary enzalutamide dose modifications may follow institutional standard practice.

    Enzalutamide is supplied as 40 mg soft gelatin capsules.

  • OleclumabDrug

    Also called MEDI9447

    Oleclumab 1500 mg will be given by IV infusion on Days 1 and 15 of each cycle.

  • DocetaxelDrug

    Also called Taxotere

    Patients in Cohort CC will receive docetaxel 75 mg/m² by IV infusion according to institutional standards of practice on Day 1 of each treatment cycle. If a patient's body surface area is greater than 2.2 m², the docetaxel dose will be adjusted to a body surface area of 2.2 m².

    The patient should be pre-medicated with oral dexamethasone 8 mg (or equivalent) twice daily starting the day prior to treatment for a total of 3 days, or according to institutional standards of practice.

Study groups in NCT02740985
Study groupRoleWhat they receive
Arm AExperimentalAZD4635 monotherapy as nanoparticle suspension 125 mg BID
Receives: Drug: AZD4635
Arm BExperimentalAZD4635 monotherapy as nanoparticle suspension 75 mg QD
Receives: Drug: AZD4635
Arm CExperimentalAZD4635 monotherapy as nanoparticle suspension 100 mg QD
Receives: Drug: AZD4635
Arm DExperimentalAZD4635 as nanoparticle suspension 75 mg QD plus durvalumab
Receives: Drug: AZD4635; Drug: Durvalumab
Arm EExperimentalAZD4635 as nanoparticle suspension 100 mg QD plus durvalumab
Receives: Drug: AZD4635; Drug: Durvalumab
Arm EAExperimentalAZD4635 as nanoparticle suspension plus enzalutamide
Receives: Drug: AZD4635; Drug: Enzalutamide
Arm AAExperimentalAZD4635 as nanoparticle suspension plus abiraterone acetate
Receives: Drug: AZD4635; Drug: Abiraterone Acetate
Arm FExperimentalAZD4635 as nanoparticle suspension plus durvaluamb in patients post immunotherapy with non-small cell lung cancer. Patients will be allocated randomly (1:1) between Arms F and G.
Receives: Drug: AZD4635; Drug: Durvalumab
Arm GExperimentalAZD4635 monotherapy as nanoparticle suspension in patients post immunotherapy with non-small cell lung cancer. Patients will be allocated randomly (1:1) between Arms F and G.
Receives: Drug: AZD4635
Arm HExperimentalAZD4635 monotherapy as nanoparticle suspension in patients post immunotherapy with other solid tumours.
Receives: Drug: AZD4635
Arm IExperimentalAZD4635 as nanoparticle suspension plus durvalumab in immunotherapy naïve patients with metastatic castration resistant prostate cancer. Patients will be allocated randomly (1:1) between Arms I and J.
Receives: Drug: AZD4635; Drug: Durvalumab
Arm JExperimentalAZD4635 monotherapy as nanoparticle suspension in immunotherapy naïve patients with metastatic castration resistant prostate cancer. Patients will be allocated randomly (1:1) between Arms I and J.
Receives: Drug: AZD4635
Arm KExperimentalAZD4635 monotherapy as nanoparticle suspension in immunotherapy naïve patients with colorectal carcinoma.
Receives: Drug: AZD4635
Arm KDExperimentalAZD4635 as nanoparticle suspension plus durvalumab in immunotherapy-naïve patients with colorectal carcinoma.
Receives: Drug: AZD4635; Drug: Durvalumab
Arm LExperimentalAZD4635 monotherapy as nanoparticle suspension in immunotherapy naïve patients with other solid tumours.
Receives: Drug: AZD4635
Arm CAExperimentalAZD4635 capsule formulation monotherapy 75 mg, 150 mg, and 200 mg QD. A lower dose of 125 mg or 100 mg may be given. The pharmacokinetics of the single dose AZD4635 capsule formulation will be characterized on Cycle 1 Day 1 in Arm CA. Steady-state pharmacokinetics will be assessed on Cycle 1 Day 15. Cycle 1 and Cycle 2 will be administered in 3-week cycles to assess the safety and dose-limiting toxicity (DLT). After Cycle 1, PKs will be collected on Day 1 of every even numbered cycle (Cycles 2, 4, and 6).
Receives: Drug: AZD4635
Arm CBExperimentalAZD4635 capsule formulation 50 mg QD or 75 mg QD plus durvalumab and oleclumab. The pharmacokinetics of AZD4635 capsule formulation will be characterized on Cycle 1, 2, and 4 (Day 1) in Arm CB. Steady-state pharmacokinetics will be assessed on Cycle 2 Day 15. Cycle 1 will be administered in a 3-week cycle to assess the safety and dose-limiting toxicity (DLT). PKs will also be collected on Day 1 of Cycles 3 and 5.
Receives: Drug: AZD4635; Drug: Durvalumab; Drug: Oleclumab
Arm CCExperimentalAZD4635 capsule formulation 50 mg QD or 75 mg QD plus docetaxel. The pharmacokinetics of the single dose AZD4635 capsule formulation will be characterized on Cycle 1 Day 1 in Arm CC. Steady-state pharmacokinetics will be assessed on Cycle 1 Day 15. Cycles will be administered in 3-week cycles to assess the safety and dose-limiting toxicity (DLT). After Cycle 1, PKs will be collected on Day 1 of every even numbered cycle (Cycles 2, 4, and 6).
Receives: Drug: AZD4635; Drug: Docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The incidence of Dose-Limiting Toxicities (DLTs) in patients receiving AZD4635 monotherapy orally.

    A Bayesian Logistic Regression Model (BLRM) based approach will be used to identify the set of AZD4635 doses where the incidence of DLTs is no larger than 33%. In each arm, up to 3 patients will be initially assessed. The dose will be escalated to the next higher dose level if all 3 patients in the previous dose level complete the DLT evaluation period without a DLT. Following the first DLT, the BLRM model will be run and the output made available to the safety review committee (SRC) to guide further dosing decisions. Each dose cohort will include a maximum of 6 patients.

    Measured: 3 weeks (One Cycle)

  2. The incidence of Dose-Limiting Toxicities (DLTs) in patients receiving AZD4635 in combination with durvalumab.

    A Bayesian Logistic Regression Model (BLRM) based approach will be used to identify the set of AZD4635 doses where the incidence of DLTs is no larger than 33%. In each arm, up to 3 patients will be initially assessed. The dose will be escalated to the next higher dose level if all 3 patients in the previous dose level complete the DLT evaluation period without a DLT. Following the first DLT, the BLRM model will be run and the output made available to the safety review committee (SRC) to guide further dosing decisions. Each dose cohort will include a maximum of 6 patients.

    Measured: 7 weeks (Including Cycle 0)

  3. The incidence of Dose-Limiting Toxicities (DLTs) in patients receiving AZD4635 in combination with either abiraterone acetate or enzalutamide.

    The starting dose of AZD4635 is 50 mg PO QD. Escalations of AZD4635 will be made based on emerging data, including nonclinical or clinical evidence, and assessment by the Safety Review Committee (SRC). Each dose cohort will include a maximum of 6 evaluable patients. An additional 6 patients will be treated at selected dose(s) to obtain further the safety, tolerability, and PK.

    Measured: 21 days (Cycle 1)

  4. The incidence of adverse events

    Safety and tolerability will be assessed in monotherapy and combination cohorts by determining the incidence of adverse events, including abnormal laboratory results, physical examination findings, vital signs, and urinalysis.

    Measured: Patients will be followed for either 21 days in Cycles 1 and 2 or 28 days in Cycles 3 and beyond to determine the incidence of adverse events.

Secondary outcomes (22)

  1. Peak plasma concentration (Cmax) of AZD4635 after single-dose administration in Cycle 0

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points for up to one-week following a single-dose of AZD4635 (Cycle 0). The multiple-dose PK sampling will commence with Cycle 1 Day 1.

  2. Time to peak plasma concentration (tmax) of AZD4635 after single-dose administration in Cycle 0

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points for up to one-week following a single-dose of AZD4635 (Cycle 0). The multiple-dose PK sampling will commence with Cycle 1 Day 1.

  3. Terminal elimination rate constant (λz) of AZD4635 after single-dose administration in Cycle 0

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points for up to one-week following a single-dose of AZD4635 (Cycle 0). The multiple-dose PK sampling will commence with Cycle 1 Day 1.

  4. Terminal elimination half-life (t½λz) of AZD4635 after single-dose administration in Cycle 0

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points for up to one-week following a single-dose of AZD4635 (Cycle 0). The multiple-dose PK sampling will commence with Cycle 1 Day 1.

  5. Area under the plasma concentration-time curve following single dose administration of AZD4635 in Cycle 0

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points for up to one-week following a single-dose of AZD4635 (Cycle 0). The multiple-dose PK sampling will commence with Cycle 1 Day 1

  6. Apparent plasma clearance (CL/F) after single-dose administration of AZD4635 in Cycle 0

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points for up to one-week following a single-dose of AZD4635 (Cycle 0). The multiple-dose PK sampling will commence with Cycle 1 Day 1.

  7. Apparent volume of distribution (Vz/F) after single-dose administration of AZD4635 in Cycle 0

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points for up to one-week following a single-dose of AZD4635 (Cycle 0). The multiple-dose PK sampling will commence with Cycle 1 Day 1.

  8. Mean residence time (MRT) of AZD4635 after single-dose administration in Cycle 0

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points for up to one-week following a single-dose of AZD4635 (Cycle 0). The multiple-dose PK sampling will commence with Cycle 1 Day 1.

  9. Renal clearance (CLR) of AZD4635 after single-dose administration in Cycle 0

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points for up to one-week following a single-dose of AZD4635 (Cycle 0). The multiple-dose PK sampling will commence with Cycle 1 Day 1.

  10. Amount of AZD4635 excreted unchanged in urine (Ae) after single-dose administration in Cycle 0

    The amount of AZD4635 (and metabolites) in urine will be determined in all patients. Pooled collections of urine 0 to 4 hours post dose, 4 to 8 hours post dose, and 8 to 24 hours post dose. Patients will collect all urine at home and bring the 8 to 24 hour pooled collection to the clinic. The total volume of each pooled sample will be recorded after which a 10 mL aliquot will be taken for analysis.

    Measured: Urine will be collected and pooled at specific intervals: pre-dose (spot urine), 0 to 4 hours, 4 to 8 hours, and 8 to 24 hours.

  11. Fraction of AZD4635 excreted unchanged in urine (fe) after single-dose administration in Cycle 0

    The amount of AZD4635 (and metabolites) in urine will be determined in all patients. Pooled collections of urine 0 to 4 hours post dose, 4 to 8 hours post dose, and 8 to 24 hours post dose. Patients will collect all urine at home and bring the 8 to 24 hour pooled collection to the clinic. The total volume of each pooled sample will be recorded after which a 10 mL aliquot will be taken for analysis.

    Measured: Urine will be collected and pooled at specific intervals: pre-dose (spot urine), 0 to 4 hours, 4 to 8 hours, and 8 to 24 hours.

  12. Peak plasma concentration of AZD4635 at steady state (Cmax, ss) following multiple-doses on Cycle 1 Day 15 in monotherapy arms and Cycle 1 Day 1 and Cycle 3 Day 15 in combination therapy arms.

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points in the multiple-dose portion of the study beginning with Cycle 1 Day 1. Sampling be done on 1 of 3 schedules: i) Intensive sampling, ii) ECG-matched sampling, or iii) Sparse sampling.

  13. Time to peak plasma concentration of AZD4635 at steady state (tmax, ss) following multiple-doses on Cycle 1 Day 15 in monotherapy arms and Cycle 1 Day 1 and Cycle 3 Day 15 in combination therapy arms.

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points in the multiple-dose portion of the study beginning with Cycle 1 Day 1. Sampling be done on 1 of 3 schedules: i) Intensive sampling, ii) ECG-matched sampling, or iii) Sparse sampling.

  14. Minimum plasma concentration of AZD4635 at steady state (Cmin, ss) following multiple-doses on Cycle 1 Day 15 in monotherapy arms and Cycle 1 Day 1 and Cycle 3 Day 15 in combination therapy arms.

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points in the multiple-dose portion of the study beginning with Cycle 1 Day 1. Sampling be done on 1 of 3 schedules: i) Intensive sampling, ii) ECG-matched sampling, or iii) Sparse sampling.

  15. Area under the plasma concentration-time curve within the dosing interval (AUCtau) following multiple-doses on Cycle 1 Day 15 in monotherapy arms and Cycle 1 Day 1 and Cycle 3 Day 15 in combination therapy arms.

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points in the multiple-dose portion of the study beginning with Cycle 1 Day 1. Sampling be done on 1 of 3 schedules: i) Intensive sampling, ii) ECG-matched sampling, or iii) Sparse sampling.

  16. Apparent plasma clearance at steady state (CLss/F) following multiple-doses on Cycle 1 Day 15 in monotherapy arms and Cycle 1 Day 1 and Cycle 3 Day 15 in combination therapy arms.

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points in the multiple-dose portion of the study beginning with Cycle 1 Day 1. Sampling be done on 1 of 3 schedules: i) Intensive sampling, ii) ECG-matched sampling, or iii) Sparse sampling.

  17. Extent of accumulation of AZD4635 (Rac) after multiple dosing

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points in the multiple-dose portion of the study beginning with Cycle 1 Day 1. Sampling will be done on 1 of 3 schedules: i) Intensive sampling, ii) ECG-matched sampling, or iii) Sparse sampling.

  18. Time dependency of AZD4635 pharmacokinetic parameters (TCP) after multiple dosing.

    The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

    Measured: Samples will be collected at pre-specified time points in the multiple-dose portion of the study beginning with Cycle 1 Day 1. Sampling will be done on 1 of 3 schedules: i) Intensive sampling, ii) ECG-matched sampling, or iii) Sparse sampling.

  19. The concentration of durvalumab and anti-drug antibody in plasma when given in combination with AZD4635

    Plasma concentration of durvalumab and anti-drug antibody will be determined by inspection of the concentration-time profile. The date and time of collection of each sample will be recorded.

    Measured: Preinfusion and end of infusion on Day 1 of Cycles 2 and 5. Preinfusion of Day 1 of Cycles 3 and 8 and 90-days after the last dose of durvalumab.

  20. The effect of AZD4635 on QTc interval

    Twelve-lead ECGs will be obtained after the patient has been resting supine for at least 10 minutes. For each time point 3 ECG recordings should be taken at about 2- to 5 minute intervals.

    Measured: In screening and on Days 1, 2 and 15 in Cycle 1, Day 1 of each cycle thereafter, and at the end of treatment and at each progression-free follow-up visit.

  21. Tumour Response

    Categorization of objective tumour response assessment will be based on the RECIST Version 1.1 guidelines for response (CR (complete response), PR (partial response), SD (stable disease), and PD (progressive disease).

    For patients who only have non-measurable disease at baseline, categorization of objective tumour response assessment will be based on the RECIST Version 1.1 guideline for response for non-target lesions (NTLs): CR, PD, and Non CR/Non PD.

    Measured: Tumour response will be assessed 6 weeks after the start of treatment and then every 8 weeks; after 18 months, assessments will be every 12 weeks.

  22. Progression free survival

    Progression free survival is defined as the time interval from the first dose of AZD4635 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from study treatment. Subjects who have not progressed or died at the time of analysis will be censored at the time of the last evaluable RECIST assessment.

    Measured: Patients will be restaged after 6 weeks (+/- 7 days) and every 8 weeks (+/- 7 days) thereafter, at the end of treatment visit if required, and at progression free follow up visits if they discontinue study treatment prior to progression.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Apr 2016 (estimated)
  2. Study start17 Jun 2016
  3. Primary completion31 Dec 2020
  4. Study completion31 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
313 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02740985
Sponsor's protocol ID
D8730C00001
Other IDs
REFMAL 435
Status last verified
May 2023
First submitted
29 Feb 2016
Last updated
26 May 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD4635, Durvalumab and Abiraterone Acetate in people with Advanced Solid Malignancies and Non-Small Cell Lung Cancer (NSCLC), run by AstraZeneca at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 45 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The incidence of Dose-Limiting Toxicities (DLTs) in patients receiving AZD4635 monotherapy orally. (time frame: 3 weeks (One Cycle)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02740985.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2023.

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