Clear Cell Renal Cell CancerPhase 1NCT04504669
First Time in Human Study of AZD8701 With or Without Durvalumab in Participants With Advanced Solid Tumours
A Phase 1 study testing AZD8701 and Durvalumab in people with Clear Cell Renal Cell Cancer and Non-Small-Cell Lung Cancer, run by AstraZeneca at 13 sites in 4 countries.
Trial summary
The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of AZD8701 Alone and in Combination with Durvalumab (MEDI4736) in Adult Subjects with Select Advanced Solid Tumors Read more about this study
- Who is it for?
- Ages 18 to 101 years
- Conditions the study is for
- Clear Cell Renal Cell Cancer, Non-Small-Cell Lung Cancer, Triple Negative Breast Neoplasms
- What is being tested?
- AZD8701 and Durvalumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 13 sitesin 4 countries
- Study dates
- 18 Aug 2020to 7 Oct 2024
- 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 101 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The study is comprised of 2 main parts Monotherapy (AZD8701) and Combined Therapy (AZD8701 and Durvalumab).
- Histological or cytological confirmation of a solid, malignant tumour including HNSCC, TNBC, NSCLC, ccRCC, gastroesophageal cancer, melanoma, cervical cancer, SCLC, and/or participants with other solid tumours who have demonstrated a response to prior anti-PD-(L)1 treatment
- Participant with progressive disease that is refractory to standard therapies or for which no standard therapies exist and a clinical trial is the best option for next treatment based on prior response and/or tolerability to standard of care
- Non Small Lung Cancer Participants who have received prior PD(L)1 treatment. Clear Cell Renal Cancer Participants who have not received prior PD(L)1 treatment.
- Triple negative Breast Cancer participants who have who have not received prior PD(L)1 treatment.
- General inclusion criteria:
Show all 16Show fewer
- Must be 18 year old at the time of screening
- Body weight > 35 kg
- Male and Female participants of childbearing potential must use effective methods of contraception
- Capable of giving signed informed consent
- ECOG performance status of 0 to 1
- A serum albumin > 30g/L
- Life expectancy of > 12 weeks
- At least 1 lesion, that qualifies as a RECIST 1.1 target lesion at baseline. Tumour assessment by CT scan or MRI must be performed within 28 days prior to treatment.
- Participants must provide a new or previous tumour sample
- Adequate organ system functions
Who cannot join
- A condition that, in the opinion of the Investigator, would interfere with evaluation of the study intervention or interpretation of participant safety or study results
- History of allogeneic organ transplantation.
- Active or prior documented autoimmune or inflammatory disorders Uncontrolled intercurrent illness
- Significant cardiac disease
- History of another primary malignancy except for
- Malignancy treated with curative intent and with no known active disease ≥ 5 years
Show all 30Show fewer
- non-melanoma skin cancer
- Adequately treated carcinoma in situ without evidence of disease.
- Participant with previous or confirmed Covid 19 diagnosis requiring significant medical intervention
- Current clinical signs and symptoms consistent with COVID-19 or confirmed current infection by appropriate laboratory test within the last 4 weeks prior to screening
- Any major unresolved toxicity from previous anticancer therapy
- Known allergy or hypersensitivity to any of the study interventions or any of the study intervention excipients.
- Prior/Concomitant Therapy
- Receipt of the last dose of anticancer therapy within 5 half-lives or ≤ 21 days prior to the first dose of study
- Prior treatment with potential Treg depletion therapies including agents targeting OX40 or CD357 (GITR) for 90 days prior to enrolment on study.
- Participants who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4:
- Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
- All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline
- Must not have experienced a ≥ Grade 3 imAE or a neurologic or ocular imAE of any grade while receiving prior immunotherapy.
- Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE
- Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug. b. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection).
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
- Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study intervention.
- Major surgical procedure within 28 days prior to the first dose
- Participants receiving anticoagulation therapy with vitamin K antagonists (eg warfarin)
- Participation in another clinical study with study intervention administered in the last 30 days
- Female participants who are pregnant or breastfeeding or male and female participants of reproductive potential who are not willing to employ effective birth control
Trial locations and contacts
13 sites in 4 countries.
13 sites in 4 countries
United States6 sites
Research Site
Baltimore, Maryland, 21287
Research Site
Franklin, Tennessee, 37067
Research Site
Houston, Texas, 77030
Research Site
Huntersville, North Carolina, 28078
Research Site
Madison, Wisconsin, 53792
Research Site
St Louis, Missouri, 63110
Spain4 sites
Research Site
Barcelona, 08035
Research Site
L'Hospitalet de Llobregat, 08907
Research Site
Madrid, 28027
Research Site
Madrid, 28041
About this study
Official title: A Phase I First-in-Human Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of AZD8701 Administered Intravenously as Monotherapy and in Combination With Durvaluamb (MEDI4736) in Participants With Advanced Solid Tumours.
The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of AZD8701 Alone and in Combination with Durvalumab (MEDI4736) in Adult Subjects with Select Advanced Solid Tumors
Read the detailed description
This is a Phase I, First in Human, multicentre, open-label, multiple arm study with dose escalations and expansions at selected doses. Dose-escalation will occur with AZD8701 in monotherapy (Part 1) and in combination with durvalumab (Part 3) in selected participants with HNSCC, TNBC, NSCLC, ccRCC, gastroesophageal cancer, melanoma, cervical cancer, small-cell lung cancer and/or participants with solid tumours who have demonstrated a response to prior PD-(L)1 treatment.
Disease specific expansions will occur with a selected dose of AZD8701 in participants with NSCLC (Part 2) and with a selected dose of AZD8701 and durvalumab in participants with TNBC and clear cell RCC (Part 4).
- Conditions
- Clear Cell Renal Cell Cancer, Non-Small-Cell Lung Cancer, Triple Negative Breast Neoplasms, Squamous Cell Cancer of Head and Neck, Small Cell Lung Cancer, Gastroesophageal Cancer
- Being tested
- AZD8701, Durvalumab
- Keywords
- Solid Tumours, Durvalumab, MEDI4736, AZD8701, Non Small cell Lung cancer, ccRenal Cancer, TNBC, first time in human, PD-L1, T regulatory cells, FOXP3
- Medical subject headings
- Carcinoma, Renal Cell, Carcinoma, Non-Small-Cell Lung, Triple Negative Breast Neoplasms, Small Cell Lung Carcinoma, Melanoma, Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD8701Drug
FOXP3 antisense oligonucleotide
DurvalumabBiological
Also called MEDI4736
anti PDL-1 monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| Monotherapy | Experimental | Participants will receive AZD8701 intravenously, on Day 1, 3, 5 and 8 and then weekly for a maximum of 2 years. Receives: Drug: AZD8701 |
| Combination Therapy | Experimental | Participants will receive AZD8701 (intravenously, on Day 1, 3, 5 and 8 and then weekly) and durvalumab (MEDI4736) intravenously monthly for a maximum of 2 years. Receives: Drug: AZD8701; Biological: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated dose (or optimal dose or maximum feasible dose) and RP2D of AZD8701 as monotherapy and in combination with Durvalumab assessed through evaluation of AEs and SAEs
Determined according to Incidence and treatment related AEs and SAEs
Measured: From screening until 105 days after last dose of study treatment
Maximum Tolerated dose (or optimal dose or maximum feasible dose) and RP2D of AZD8701 as monotherapy and in combination with Durvalumab assessed through evaluation of Dose Limiting Toxicities (DLTs)
Determined according to Incidence of DLTs (during the first 28 day cycle)
Measured: First 28 day cycle
Maximum Tolerated dose (or optimal dose or maximum feasible dose) and RP2D of AZD8701 as monotherapy and in combination with Durvalumab assessed through evaluation of vital signs and abnormal laboratory parameters
Determined according to Incidence of abnormal vital signs and laboratory parameters
Measured: From screening until 105 days after last dose of study treatment
Incidence of AEs and SAEs related to AZD8701 as monotherapy and in combination with Durvalumab in disease specific expansions treated at the MTD/OBD/MFD
Safety and tolerability of the MTD/OBD/MFD assessed through incidence of AEs and SAEs
Measured: From screening until 105 days after last dose of study treatment
Objective Response Rate according to RECIST 1.1 by investigator assessment in disease specific expansions treated at the MTD/OB/MFD
The proportion of subjects achieving a confirmed complete or partial response according to RECIST 1.1 by investigator assessment
Measured: Every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death, start of subsequent anti-cancer therapy or end of study (for max 42 months)
Secondary outcomes (16)
Progression-free survival according to RECIST 1.1 by investigator assessment
Time from start of study treatment to the date of objective disease progression or death (by any cause in the absence of progression)
Measured: every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death or end of study (for max 42 months)
Duration of Response according to RECIST 1.1 by investigator assessment
Time from first documented response (that is subsequently confirmed) to the date of objective disease progression or death (by any cause in the absence of progression)
Measured: every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death or end of study (for max 42 months)
Disease Control Rate at 16 weeks according to RECIST 1.1 by investigator assessment
The proportion of subjects with a best response of CR or PR in the first 16 weeks or SD for at least 16 weeks according to RECIST 1.1 by investigator assessment
Measured: Every 8 weeks from start of treatment until earlier of progression, death or start of subsequent anti-cancer therapy (for up to 24 weeks). Subjects followed to 24 weeks for assessment of SD for 16 weeks from first tumour assessment at 8 weeks
Time to Response according to RECIST 1.1 by investigator assessment
Time from the start of study treatment until the date of first documented response (which is subsequently confirmed)
Measured: Every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death or end of study (for max 42 months)
Best percentage change in tumour size according to RECIST 1.1 by investigator assessment
Best percentage change from baseline in sum of the diameters of target lesions
Measured: Every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death, start of subsequent anti-cancer therapy or end of study (for max 42 months)
Overall Survival at 18 months
The survival rate of subjects at 18 months from start of treatment
Measured: From start of treatment until the earlier of death or end of study (for max of 42 months). Each subject is followed for a minimum of 18 months and the landmark OS rate at 18 months will be estimated using a Kaplan-Meier analysis
Maximum concentration (Cmax) of AZD8701 in plasma when administered as monotherapy and in combination with Durvalumab
Maximum concentration (Cmax) of AZD8701 in plasma
Measured: Cycle 1: Day 1, 2, 3, 5, 8. Cycle 2: Day 1, 22, 23. Cycle 3 & 4: Day 1 and at 105 day follow up (up to 28 months)
Time to maximum concentration (tmax) of AZD8701 in plasma when administered as monotherapy and in combination with Durvalumab
Time to maximum concentration (tmax) of AZD8701 in plasma
Measured: Cycle 1: Day 1, 2, 3, 5, 8. Cycle 2: Day 1, 22, 23. Cycle 3 & 4: Day 1 and at 105 day follow up (up to 28 months)
Exposure to AZD8701 through measurement of area under the curve (AUC) in plasma when administered as monotherapy and in combination with Durvalumab
Exposure to AZD8701 through measurement of area under the curve (AUC) in plasma
Measured: Cycle 1: Day 1, 2, 3, 5, 8. Cycle 2: Day 1, 22, 23. Cycle 3 & 4: Day 1 and at 105 day follow up (up to 28 months)
Maximum concentration (Cmax) of AZD8701 in urine when administered as monotherapy and in combination with Durvalumab
Maximum concentration (Cmax) of AZD8701 in urine
Measured: Cycle 1: Day 1, 2. Cycle 2: Day 22, 23 (up to 2 months)
Time to maximum concentration (tmax) of AZD8701 in urine when administered as monotherapy and in combination with Durvalumab
Time to maximum concentration (tmax) of AZD8701 in urine
Measured: Cycle 1: Day 1, 2. Cycle 2: Day 22, 23 (up to 2 months)
Exposure to AZD8701 through measurement of area under the curve (AUC) in urine when administered as monotherapy and in combination with Durvalumab
Exposure to AZD8701 through measurement of area under the curve (AUC) in urine
Measured: Cycle 1: Day 1, 2. Cycle 2: Day 22, 23 (up to 2 months)
Urine concentrations of AZD8701 to assess renal clearance when administered as monotherapy and in combination with Durvalumab
Urine samples will be collected to assess urine concentrations of AZD8701 at a series of timepoints to derive renal clearance
Measured: Cycle 1: Day 1, 2. Cycle 2: Day 22, 23 (up to 2 months)
Maximum concentration (Cmax) of Durvalumab in serum when administered in combination with AZD8701
Maximum concentration (Cmax) of Durvalumab in serum
Measured: Cycle 1, 2, 3, 4 on Day 1 and 105 follow up (up to 28 months)
Minimum concentration (Cmin) of Durvalumab in serum when administered in combination with AZD8701
Minimum concentration (Cmin) of Durvalumab in serum
Measured: Cycle 1, 2, 3, 4 on Day 1 and 105 follow up (up to 28 months)
Change in FOXP3 mRNA expression
Percentage change in FOXP3 mRNA expression from pre-treatment (baseline) to post treatment
Measured: From day 1 to day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2020
- Study start18 Aug 2020
- Primary completion7 Oct 2024
- Study completion7 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clear Cell Renal Cell CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Sequential
- Model description
- This is a Phase I, FIH, multicentre, open-label, multiple arm study. Dose-escalation will occur with AZD8701 in monotherapy and in combination with durvalumab in selected participants with HNSCC, TNBC, NSCLC, ccRCC, gastroesophgeal cancer, melanoma, cervical cancer, small-cell lung cancer and/or participants with solid tumours who have demonstrated a response to prior PD-(L)1 treatment. Disease specific expansions will occur with a selected dose of AZD8701 in participants with NSCLC and with a selected dose of AZD8701 and durvalumab in participants with TNBC and clear cell RCC.
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04504669
- Sponsor's protocol ID
- D9950C00001
- Other IDs
- 04504669, 2019-004539-22, 2019
- Status last verified
- Nov 2024
- First submitted
- 16 Jul 2020
- Last updated
- 5 Nov 2024
- 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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Publications
Revenko A, Carnevalli LS, Sinclair C, Johnson B, Peter A, Taylor M, Hettrick L, Chapman M, Klein S, Solanki A, Gattis D, Watt A, Hughes AM, Magiera L, Kar G, Ireland L, Mele DA, Sah V, Singh M, Walton J, Mairesse M, King M, Edbrooke M, Lyne P, Barry ST, Fawell S, Goldberg FW, MacLeod AR. Direct targeting of FOXP3 in Tregs with AZD8701, a novel antisense oligonucleotide to relieve immunosuppression in cancer. J Immunother Cancer. 2022 Apr;10(4):e003892. doi: 10.1136/jitc-2021-003892.
PubMed 35387780
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I First-in-Human Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of AZD8701 Administered Intravenously as Monotherapy and in Combination With Durvaluamb (MEDI4736) in Participants With Advanced Solid Tumours.
- ClinicalTrials.gov ID
- NCT04504669
- Acronym / sponsor ID
- D9950C00001
- Conditions
- Clear Cell Renal Cell Cancer, Non-Small-Cell Lung Cancer, Triple Negative Breast Neoplasms, Squamous Cell Cancer of Head and Neck, Small Cell Lung Cancer, Gastroesophageal Cancer
- Keywords
- Solid Tumours, Durvalumab, MEDI4736, AZD8701, Non Small cell Lung cancer, ccRenal Cancer, TNBC, first time in human
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 18 Aug 2020 (actual)
- Primary completion
- 7 Oct 2024 (actual)
- Study completion
- 7 Oct 2024 (actual)
- First posted
- 7 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of AZD8701 Alone and in Combination with Durvalumab (MEDI4736) in Adult Subjects with Select Advanced Solid Tumors
Detailed description
This is a Phase I, First in Human, multicentre, open-label, multiple arm study with dose escalations and expansions at selected doses. Dose-escalation will occur with AZD8701 in monotherapy (Part 1) and in combination with durvalumab (Part 3) in selected participants with HNSCC, TNBC, NSCLC, ccRCC, gastroesophageal cancer, melanoma, cervical cancer, small-cell lung cancer and/or participants with solid tumours who have demonstrated a response to prior PD-(L)1 treatment.
Disease specific expansions will occur with a selected dose of AZD8701 in participants with NSCLC (Part 2) and with a selected dose of AZD8701 and durvalumab in participants with TNBC and clear cell RCC (Part 4).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a Phase I, FIH, multicentre, open-label, multiple arm study. Dose-escalation will occur with AZD8701 in monotherapy and in combination with durvalumab in selected participants with HNSCC, TNBC, NSCLC, ccRCC, gastroesophgeal cancer, melanoma, cervical cancer, small-cell lung cancer and/or participants with solid tumours who have demonstrated a response to prior PD-(L)1 treatment. Disease specific expansions will occur with a selected dose of AZD8701 in participants with NSCLC and with a selected dose of AZD8701 and durvalumab in participants with TNBC and clear cell RCC.
| Arm | Type | Receives |
|---|---|---|
| Monotherapy | Experimental | Drug: AZD8701Participants will receive AZD8701 intravenously, on Day 1, 3, 5 and 8 and then weekly for a maximum of 2 years. |
| Combination Therapy | Experimental | Drug: AZD8701, Biological: DurvalumabParticipants will receive AZD8701 (intravenously, on Day 1, 3, 5 and 8 and then weekly) and durvalumab (MEDI4736) intravenously monthly for a maximum of 2 years. |
Who may qualify
- Ages
- 18 to 101 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- The study is comprised of 2 main parts Monotherapy (AZD8701) and Combined Therapy (AZD8701 and Durvalumab).
- Histological or cytological confirmation of a solid, malignant tumour including HNSCC, TNBC, NSCLC, ccRCC, gastroesophageal cancer, melanoma, cervical cancer, SCLC, and/or participants with other solid tumours who have demonstrated a response to prior anti-PD-(L)1 treatment
- Participant with progressive disease that is refractory to standard therapies or for which no standard therapies exist and a clinical trial is the best option for next treatment based on prior response and/or tolerability to standard of care
- Non Small Lung Cancer Participants who have received prior PD(L)1 treatment. Clear Cell Renal Cancer Participants who have not received prior PD(L)1 treatment.
- Triple negative Breast Cancer participants who have who have not received prior PD(L)1 treatment.
Key exclusion criteria (30 listed)
- A condition that, in the opinion of the Investigator, would interfere with evaluation of the study intervention or interpretation of participant safety or study results
- History of allogeneic organ transplantation.
- Active or prior documented autoimmune or inflammatory disorders Uncontrolled intercurrent illness
- Significant cardiac disease
- History of another primary malignancy except for
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD8701FOXP3 antisense oligonucleotide | Drug | Combination Therapy, Monotherapy |
| DurvalumabAlso: MEDI4736anti PDL-1 monoclonal antibody | Biological | Combination Therapy |
Primary outcome
Maximum Tolerated dose (or optimal dose or maximum feasible dose) and RP2D of AZD8701 as monotherapy and in combination with Durvalumab assessed through evaluation of AEs and SAEs
Time frame: From screening until 105 days after last dose of study treatment
Determined according to Incidence and treatment related AEs and SAEs
Maximum Tolerated dose (or optimal dose or maximum feasible dose) and RP2D of AZD8701 as monotherapy and in combination with Durvalumab assessed through evaluation of Dose Limiting Toxicities (DLTs)
Time frame: First 28 day cycle
Determined according to Incidence of DLTs (during the first 28 day cycle)
Maximum Tolerated dose (or optimal dose or maximum feasible dose) and RP2D of AZD8701 as monotherapy and in combination with Durvalumab assessed through evaluation of vital signs and abnormal laboratory parameters
Time frame: From screening until 105 days after last dose of study treatment
Determined according to Incidence of abnormal vital signs and laboratory parameters
Incidence of AEs and SAEs related to AZD8701 as monotherapy and in combination with Durvalumab in disease specific expansions treated at the MTD/OBD/MFD
Time frame: From screening until 105 days after last dose of study treatment
Safety and tolerability of the MTD/OBD/MFD assessed through incidence of AEs and SAEs
Objective Response Rate according to RECIST 1.1 by investigator assessment in disease specific expansions treated at the MTD/OB/MFD
Time frame: Every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death, start of subsequent anti-cancer therapy or end of study (for max 42 months)
The proportion of subjects achieving a confirmed complete or partial response according to RECIST 1.1 by investigator assessment
16 secondary outcomes
Progression-free survival according to RECIST 1.1 by investigator assessment
Time frame: every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death or end of study (for max 42 months)
Duration of Response according to RECIST 1.1 by investigator assessment
Time frame: every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death or end of study (for max 42 months)
Disease Control Rate at 16 weeks according to RECIST 1.1 by investigator assessment
Time frame: Every 8 weeks from start of treatment until earlier of progression, death or start of subsequent anti-cancer therapy (for up to 24 weeks). Subjects followed to 24 weeks for assessment of SD for 16 weeks from first tumour assessment at 8 weeks
Time to Response according to RECIST 1.1 by investigator assessment
Time frame: Every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death or end of study (for max 42 months)
Best percentage change in tumour size according to RECIST 1.1 by investigator assessment
Time frame: Every 8 weeks (first 48 weeks) and then every 12 weeks from start of treatment until the earlier of progression, death, start of subsequent anti-cancer therapy or end of study (for max 42 months)
Overall Survival at 18 months
Time frame: From start of treatment until the earlier of death or end of study (for max of 42 months). Each subject is followed for a minimum of 18 months and the landmark OS rate at 18 months will be estimated using a Kaplan-Meier analysis
Maximum concentration (Cmax) of AZD8701 in plasma when administered as monotherapy and in combination with Durvalumab
Time frame: Cycle 1: Day 1, 2, 3, 5, 8. Cycle 2: Day 1, 22, 23. Cycle 3 & 4: Day 1 and at 105 day follow up (up to 28 months)
Time to maximum concentration (tmax) of AZD8701 in plasma when administered as monotherapy and in combination with Durvalumab
Time frame: Cycle 1: Day 1, 2, 3, 5, 8. Cycle 2: Day 1, 22, 23. Cycle 3 & 4: Day 1 and at 105 day follow up (up to 28 months)
Exposure to AZD8701 through measurement of area under the curve (AUC) in plasma when administered as monotherapy and in combination with Durvalumab
Time frame: Cycle 1: Day 1, 2, 3, 5, 8. Cycle 2: Day 1, 22, 23. Cycle 3 & 4: Day 1 and at 105 day follow up (up to 28 months)
Maximum concentration (Cmax) of AZD8701 in urine when administered as monotherapy and in combination with Durvalumab
Time frame: Cycle 1: Day 1, 2. Cycle 2: Day 22, 23 (up to 2 months)
Time to maximum concentration (tmax) of AZD8701 in urine when administered as monotherapy and in combination with Durvalumab
Time frame: Cycle 1: Day 1, 2. Cycle 2: Day 22, 23 (up to 2 months)
Exposure to AZD8701 through measurement of area under the curve (AUC) in urine when administered as monotherapy and in combination with Durvalumab
Time frame: Cycle 1: Day 1, 2. Cycle 2: Day 22, 23 (up to 2 months)
Urine concentrations of AZD8701 to assess renal clearance when administered as monotherapy and in combination with Durvalumab
Time frame: Cycle 1: Day 1, 2. Cycle 2: Day 22, 23 (up to 2 months)
Maximum concentration (Cmax) of Durvalumab in serum when administered in combination with AZD8701
Time frame: Cycle 1, 2, 3, 4 on Day 1 and 105 follow up (up to 28 months)
Minimum concentration (Cmin) of Durvalumab in serum when administered in combination with AZD8701
Time frame: Cycle 1, 2, 3, 4 on Day 1 and 105 follow up (up to 28 months)
Change in FOXP3 mRNA expression
Time frame: From day 1 to day 29
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2024.
- Derived from this study: PubMed 35387780Revenko A, Carnevalli LS, Sinclair C, Johnson B, Peter A, Taylor M, Hettrick L, Chapman M, Klein S, Solanki A, Gattis D, Watt A, Hughes AM, Magiera L, Kar G, Ireland L, Mele DA, Sah V, Singh M, Walton J, Mairesse M, King M, Edbrooke M, Lyne P, Barry ST, Fawell S, Goldberg FW, MacLeod AR. Direct targeting of FOXP3 in Tregs with AZD8701, a novel antisense oligonucleotide to relieve immunosuppression in cancer. J Immunother Cancer. 2022 Apr;10(4):e003892. doi: 10.1136/jitc-2021-003892.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: 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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Carcinoma, Renal Cell
Active, not recruitingPhase 1/2
Pazopanib Hydrochloride and Bevacizumab in Treating Patients With Previously Untreated Metastatic Kidney Cancer
Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer
RecruitingPhase 2
Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
Metastatic Melanoma, Advanced Locoregional Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD8701 and Durvalumab in people with Clear Cell Renal Cell Cancer and Non-Small-Cell Lung Cancer, run by AstraZeneca at 13 sites in 4 countries.
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 16 inclusion and 30 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 5 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Spain, France, Canada. 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?
Maximum Tolerated dose (or optimal dose or maximum feasible dose) and RP2D of AZD8701 as monotherapy and in combination with Durvalumab assessed through evaluation of AEs and SAEs (time frame: From screening until 105 days after last dose of study treatment). The study lists 5 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 NCT04504669, which also lists 1 linked publication.
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 5 Nov 2024.