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NCT Number: NCT04999969

Safety, Pharmacokinetics and Clinical Activity of AZD0171 in Combination With Durvalumab and Chemotherapy in 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).

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Locally Advanced or Metastatic Solid Tumours

Age range

18 year–130 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Research Site, Barrie, Ontario, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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
  • 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)

Treatment and study plan

AZD0171

Drug

AZD0171

Other names: MSC-1

Durvalumab

Drug

Durvalumab

Other names: MEDI4736

Gemcitabine

Drug

Chemotherapy (Standard-of-Care)

Nab-paclitaxel

Drug

Chemotherapy (Standard-of-Care)

Primary outcomes

  1. Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs)

    Time frame: 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

    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.

  2. Overall Survival at 12 Months (OS-12)

    Time frame: At 12 months

    Percentage of participants alive at 12 months after initiation of study intervention per Kaplan- Meier estimate of OS at 12 months.

Secondary outcomes

  1. Objective Response Rate (ORR)

    Time frame: 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).

    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.

  2. Disease Control Rate (DCR)

    Time frame: Up to 16 weeks

    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.

  3. Duration of Response (DoR)

    Time frame: From screening until disease progression or last evaluable assessment in the absence of progression, whichever came first (up to 35 months)

    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.

  4. Median Progression Free Survival (PFS)

    Time frame: 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)

    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.

  5. Progression Free Survival at 4 Months (PFS-4)

    Time frame: At 4 months

    The percentage of participants alive and free of progression at 4 months per Kaplan-Meier estimate.

  6. Median Overall Survival (OS)

    Time frame: 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)

    The OS is defined as the time from the start of study intervention to the date of death due to any cause.

  7. Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9)

    Time frame: 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

    Mean change from baseline was assessed for serum CA19-9

  8. Number of Participants With Positive Anti-drug Antibodies (ADAs) Against AZD0171 in Serum

    Time frame: 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 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.

  9. Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Durvalumab in Serum

    Time frame: 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 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.

  10. Maximum Observed Plasma Concentration (Cmax) of AZD0171

    Time frame: Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length)

    The maximum concentration of AZD0171 was determined.

  11. Maximum Observed Plasma Concentration (Cmax) of Nab-paclitaxel

    Time frame: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)

    The Cmax of Nab-paclitaxel was determined.

  12. Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) of AZD0171

    Time frame: Cycle 1 Day 1 (each cycle is 28 days in length)

    The AUCinf of AZD0171 was determined.

  13. Area Under the Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD0171

    Time frame: Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length)

    The AUClast of AZD0171 was determined.

  14. Area Under the Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of Nab-paclitaxel

    Time frame: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)

    The AUClast of Nab-paclitaxel was determined.

  15. Area Under the Concentration-time Curve in the Dose Interval (AUCtau) of AZD0171

    Time frame: Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length)

    The AUCtau of AZD0171 was determined.

  16. Area Under the Concentration-time Curve in the Dose Interval (AUCtau) of Nab-paclitaxel

    Time frame: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)

    The AUCtau of Nab-paclitaxel was determined.

  17. Clearance (CL) of AZD0171

    Time frame: Cycle 1 Day 1 and Cycle 4 and Day 1 (each cycle is 28 days in length)

    The CL of AZD0171 was determined.

  18. Clearance (CL) of Nab-paclitaxel

    Time frame: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)

    The CL of Nab-paclitaxel was determined.

  19. Terminal Elimination Half-life (t1/2λz) of AZD0171

    Time frame: Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length)

    The t1/2λz of AZD0171 was determined.

  20. Terminal Elimination Half-life (t1/2λz) of Nab-paclitaxel

    Time frame: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)

    The t1/2λz of Nab-paclitaxel was determined.

  21. Change From Screening in Cluster of Differentiation 8 (CD8+) T Cell Tumour Infiltration in Central Tumour Region

    Time frame: In cycle 3 (each cycle was 28 days in length), subsequent to the first disease assessment scan conducted at roughly 8 weeks.

    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.

  22. Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time

    Time frame: 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)

    Serum concentration of LIF bound to AZD0171 (total LIF) was assessed.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2024
Study completion
2026
First posted
Aug 11, 2021
Registry last updated
Jun 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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