Locally Advanced or Metastatic Solid TumoursPhase 2NCT04999969
Safety, Pharmacokinetics and Clinical Activity of AZD0171 in Combination With Durvalumab and Chemotherapy in Locally Advanced or Metastatic Solid Tumours
A Phase 2 study testing AZD0171, Durvalumab and Gemcitabine in people with Locally Advanced or Metastatic Solid Tumours, run by AstraZeneca at 34 sites in 4 countries.
Trial summary
The proposed study is designed to examine the effects of AZD0171 and durvalumab in combination with standard-of-care chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Locally Advanced or Metastatic Solid Tumours
- What is being tested?
- AZD0171, Durvalumab and Gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- 34 sitesin 4 countries
- Study dates
- 10 Dec 2021to 30 Nov 2026
- Phase
- Phase 2
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
- Eastern Cooperative Oncology Group performance status of 0 or 1 at screening/enrolment
- Must have a Gustave Roussy Immune Score of 0 or 1
- Participants diagnosed with histologically confirmed metastatic pancreatic adenocarcinoma
- Participants must have at least 1 measurable lesion to be called a target lesion according to RECIST v1.1
- All participants must consent to providing sufficient archival specimen taken during metastatic stage or fresh tumour specimens for tumoural CD8+ T cell testing for enrolment
- Presence of tumoural CD8+ T cells based on a predetermined benchmarked PDAC external sample
- Normal organ and bone marrow function measured within 28 days prior to first dose of study intervention
- Body weight ≥ 35 kg
Who cannot join
- Symptomatic central nervous system metastasis or any history of leptomeningeal disease or cord compression
- A participant with an already known sensitising mutation or tumour characteristic for pancreatic cancer for which there is a preferred local standard-of-care treatment
- History of thromboembolic event within the past 3 months prior to the scheduled first dose of study intervention
- Any unresolved toxicities ≥ Grade 2 per Common Terminology Criteria for Adverse Events v5.0 from prior therapy (excluding vitiligo, alopecia, controlled diabetes)
- History of solid organ transplantation
- History of active primary immunodeficiency
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- Ongoing or an active infection, including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus. A negative COVID-19 PCR test taken within 28 days of the start of the study treatment is required.
- Uncontrolled intercurrent illness
- Participants with prior history of myocardial infarction, transient ischemic attack, coronary bypass, or stroke within the past 3 months prior to the first dose of study intervention
- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 electrocardiograms
- Active or prior documented autoimmune or inflammatory disorders
- History of another primary malignancy
- Receipt of any conventional or investigational anticancer therapy prior to the scheduled first dose of study intervention
- Prior receipt of any immune-mediated therapy
- Use of immunosuppressive medication within 14 days prior to the first dose of study intervention
- Receipt of live, attenuated vaccine within 28 days prior to the first dose of study intervention (Participants can receive non-live COVID-19 vaccines, at the discretion of the Investigator)
Trial locations and contacts
34 sites in 4 countries.
34 sites in 4 countries
United States16 sites
Research Site
Ann Arbor, Michigan, 48109
Research Site
Atlanta, Georgia, 30318
Research Site
Boston, Massachusetts, 02114
Research Site
Buffalo, New York, 14263
Research Site
Charlottesville, Virginia, 22908
Research Site
Coeur d'Alene, Idaho, 83814
Research Site
Grand Rapids, Michigan, 49503
Research Site
La Jolla, California, 92037
Research Site
Los Angeles, California, 90025
Research Site
Madison, Wisconsin, 53792
Research Site
New York, New York, 10065
Research Site
Orange, California, 92868
Research Site
Portland, Oregon, 97239
Research Site
San Antonio, Texas, 78229
Research Site
Seattle, Washington, 98195
Research Site
Ventura, California, 93003
Spain8 sites
Research Site
Badalona, 08916
Research Site
Barcelona, 08035
Research Site
Madrid, 28027
Research Site
Madrid, 28034
Research Site
Madrid, 28041
Research Site
Madrid, 28050
Research Site
Majadahonda, 28222
Research Site
Pamplona, 31008
South Korea7 sites
Research Site
Seongnam-si, 13620
Research Site
Seongnam-si, 463-712
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Research Site
Seoul, 06591
Canada3 sites
Research Site
Barrie, Ontario, L4M 6M2
Research Site
Toronto, Ontario, M4N 3M5
Research Site
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase II Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of AZD0171 in Combination With Durvalumab and Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumours
The proposed study is designed to examine the effects of AZD0171 and durvalumab in combination with standard-of-care chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC).
Read the detailed description
This is a Phase II, open-label, single arm, multicentre study to assess the safety, preliminary antitumour activity, immunogenicity, pharmacodynamics (PD), and pharmacokinetics (PK) of AZD0171 in combination with durvalumab and standard-of-care chemotherapy (gemcitabine and nab-paclitaxel) in participants with first line (1L) metastatic pancreatic ductal adenocarcinoma (mPDAC).
All participants will be treated until progressive disease or unacceptable toxicity or withdrawal of consent or another discontinuation criterion is met.
- Being tested
- AZD0171, Durvalumab, Gemcitabine, Nab-paclitaxel
- Keywords
- AZD0171, Durvalumab, Gemcitabine, Nab-paclitaxel, Leukaemia inhibitory factor, Pancreatic ductal adenocarcinoma, Immunotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD0171Drug
Also called MSC-1
AZD0171
DurvalumabDrug
Also called MEDI4736
Durvalumab
GemcitabineDrug
Chemotherapy (Standard-of-Care)
Nab-paclitaxelDrug
Chemotherapy (Standard-of-Care)
| Study group | Role | What they receive |
|---|---|---|
| AZD0171 + Durvalumab + chemotherapy | Experimental | Participants will receive AZD0171 (intravenous [IV]) along with durvalumab (IV) in combination with standard-of-care chemotherapy IV (gemcitabine and nab-paclitaxel). Receives: Drug: AZD0171; Drug: Durvalumab; Drug: Gemcitabine; Drug: Nab-paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs)
The safety and tolerability of study intervention (AZD0171, durvalumab, and standard-of-care chemotherapy) was assessed. The grading scales found in the revised National Cancer Institute CTCAE latest version was utilized for all events with an assigned CTCAE grading. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL); Grade 4: Life-threatening, urgent intervention required; Grade 5: Death related to AE.
Measured: From Cycle 1 Day 1 (each cycle was 28 days in length) until Day 90 (post last dose of study intervention), up to 34 months
Overall Survival at 12 Months (OS-12)
Percentage of participants alive at 12 months after initiation of study intervention per Kaplan- Meier estimate of OS at 12 months.
Measured: At 12 months
Secondary outcomes (22)
Objective Response Rate (ORR)
The ORR is defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) that occurred prior to the initiation of subsequent anti-cancer treatment and prior to progression. The ORR was assessed per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.
Measured: From Cycle 1 Day 1 (each cycle was 28 days in length) until initiation of subsequent anti-cancer treatment and prior to progression (up to 35 months).
Disease Control Rate (DCR)
The DCR is defined as the percentage of participants with a best overall response of confirmed CR or PR, or who had stable disease (SD) maintained for 16 weeks from first dose. DCR was assessed per RECIST v1.1 criteria.
Measured: Up to 16 weeks
Duration of Response (DoR)
The DoR is defined as the time from first documented objective response (confirmed CR or confirmed PR) until date of first documented disease progression or death (by any cause in the absence of disease progression). The DoR was assessed per RECIST v1.1 criteria.
Measured: From screening until disease progression or last evaluable assessment in the absence of progression, whichever came first (up to 35 months)
Median Progression Free Survival (PFS)
The PFS is defined as the time from first dose of study intervention until the date of objective disease progression or death (by any cause in the absence of progression), whichever was earlier. The PFS was analyzed using the Kaplan-Meier method.
Measured: From first dose of study intervention until disease progression or last evaluable assessment in the absence of progression, whichever came first (up to 35 months)
Progression Free Survival at 4 Months (PFS-4)
The percentage of participants alive and free of progression at 4 months per Kaplan-Meier estimate.
Measured: At 4 months
Median Overall Survival (OS)
The OS is defined as the time from the start of study intervention to the date of death due to any cause.
Measured: From first dose of study intervention until death (Up to 35 months) or from first dose of study intervention until last evaluable assessment (Up to 35 months)
Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9)
Mean change from baseline was assessed for serum CA19-9
Measured: Day 1 of each Cycle through Cycle 27 (each cycle was 28 days in length), at end of treatment and at Day 28 follow up (post last dose); up to 35 months
Number of Participants With Positive Anti-drug Antibodies (ADAs) Against AZD0171 in Serum
Number and percentage of participants in the below categories are provided:(i)ADA positive (+ve) at baseline and/or post-baseline visits. The percentage of these participants in a population is known as ADA prevalence(ii)ADA +ve post-baseline and not detected at baseline (treatment-induced ADA positive)(iii)Treatment-boosted ADA +ve:Baseline +ve ADA titre-boosted to a 4-fold or higher level following drug administration(iv)Treatment-emergent ADA +ve:The sum of treatment-induced ADA +ve and treatment-boosted ADA +ve. The percentage of these participants in a population is known as ADA incidence(v)Persistent +ve:ADA negative (-ve) at baseline and having at least 2 post-baseline ADA +ve measurements with ≥ 16 weeks between first and last positive, or an ADA +ve result at the last available post-baseline assessment(vi)Transient +ve:ADA -ve at baseline and at least 1 post-baseline ADA +ve measurement and not fulfilling the conditions for persistently +ve.
Measured: Cycle 1 (Days 1 and 15), Cycle 2 (Days 1 and 15), until Day 90 post last dose of study intervention (each cycle is 28 days in length), assessed up to 35 months
Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Durvalumab in Serum
Number and percentage of participants in the below categories are provided:(i)ADA positive (+ve) at baseline and/or post-baseline visits. The percentage of these participants in a population is known as ADA prevalence(ii)ADA +ve post-baseline and not detected at baseline (treatment-induced ADA positive)(iii)Treatment-boosted ADA +ve:Baseline +ve ADA titre-boosted to a 4-fold or higher level following drug administration(iv)Treatment-emergent ADA +ve:The sum of treatment-induced ADA +ve and treatment-boosted ADA +ve. The percentage of these participants in a population is known as ADA incidence(v)Persistent +ve:ADA negative (-ve) at baseline and having at least 2 post-baseline ADA +ve measurements with ≥ 16 weeks between first and last positive, or an ADA +ve result at the last available post-baseline assessment(vi)Transient +ve:ADA -ve at baseline and at least 1 post-baseline ADA +ve measurement and not fulfilling the conditions for persistently +ve.
Measured: Cycle 1 (Days 1 and 15), Cycle 2 (Days 1 and 15), until Day 90 post last dose of study intervention (each cycle is 28 days in length), assessed up to 35 months
Maximum Observed Plasma Concentration (Cmax) of AZD0171
The maximum concentration of AZD0171 was determined.
Measured: Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length)
Maximum Observed Plasma Concentration (Cmax) of Nab-paclitaxel
The Cmax of Nab-paclitaxel was determined.
Measured: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) of AZD0171
The AUCinf of AZD0171 was determined.
Measured: Cycle 1 Day 1 (each cycle is 28 days in length)
Area Under the Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD0171
The AUClast of AZD0171 was determined.
Measured: Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length)
Area Under the Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of Nab-paclitaxel
The AUClast of Nab-paclitaxel was determined.
Measured: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)
Area Under the Concentration-time Curve in the Dose Interval (AUCtau) of AZD0171
The AUCtau of AZD0171 was determined.
Measured: Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length)
Area Under the Concentration-time Curve in the Dose Interval (AUCtau) of Nab-paclitaxel
The AUCtau of Nab-paclitaxel was determined.
Measured: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)
Clearance (CL) of AZD0171
The CL of AZD0171 was determined.
Measured: Cycle 1 Day 1 and Cycle 4 and Day 1 (each cycle is 28 days in length)
Clearance (CL) of Nab-paclitaxel
The CL of Nab-paclitaxel was determined.
Measured: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)
Terminal Elimination Half-life (t1/2λz) of AZD0171
The t1/2λz of AZD0171 was determined.
Measured: Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length)
Terminal Elimination Half-life (t1/2λz) of Nab-paclitaxel
The t1/2λz of Nab-paclitaxel was determined.
Measured: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)
Change From Screening in Cluster of Differentiation 8 (CD8+) T Cell Tumour Infiltration in Central Tumour Region
The changes in CD8+ T cell tumour infiltration (on-treatment during cycle 3 minus baseline) associated with AZD0171 treatment in combination with durvalumab and chemotherapy was assessed in participants with 1L metastatic pancreatic ductal adenocarcinoma.
Measured: In cycle 3 (each cycle was 28 days in length), subsequent to the first disease assessment scan conducted at roughly 8 weeks.
Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time
Serum concentration of LIF bound to AZD0171 (total LIF) was assessed.
Measured: Cycle 1 Day 1 and Day 15, Cycle 2 Day 1 and Day 15, Cycle 3 Day 1 and Day 15, Cycle 4 Day 1 and Day 15, Cycle 5Day 1, Cycle 6 Day 1, Cycle 7 Day 1, Cycle 8 Day 1 and Cycle 11 Day 1 (each cycle is 28 days in length)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2021
- Study start10 Dec 2021
- Primary completion7 Oct 2024
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Locally Advanced or Metastatic Solid TumoursStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 126 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04999969
- Sponsor's protocol ID
- D8151C00001
- Other IDs
- 2021-002040-78
- Status last verified
- Jul 2026
- First submitted
- 3 Aug 2021
- Last updated
- 19 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- 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.