Clinical trial NCT04999969: Safety, Pharmacokinetics and Clinical Activity of AZD0171 in Combination With Durvalumab and Chemotherapy in Locally Advanced or Metastatic Solid Tumours
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Locally Advanced or Metastatic Solid Tumours
Keywords: AZD0171
Durvalumab
Gemcitabine
Nab-paclitaxel
Leukaemia inhibitory factor
Pancreatic ductal adenocarcinoma
Immunotherapy
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-08-11
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of participants with adverse events (AEs), immune mediated AEs (imAEs) and serious AEs (SAEs)
timeFrame: Until Day 90 (post last dose of study intervention on Day 15)
measure: Overall survival at 12 months (OS-12)
timeFrame: Up to 12 months
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 24 months
measure: Disease control rate (DCR)
timeFrame: Up to 24 months
measure: Duration of response (DoR)
timeFrame: Up to 24 months
measure: Median progression free survival (PFS)
timeFrame: Up to 24 months
measure: PFS at 4 months (PFS-4)
timeFrame: 4 months
measure: Median overall survival (OS)
timeFrame: Up to 24 months
measure: Number of participants with change from Baseline in serum levels of carbohydrate antigen 19-9 (CA19-9)
timeFrame: From Screening (Day -28 to Day -1) until Day 28 post last dose of study intervention on Day 15
measure: Number of participants developing detectable anti-drug antibodies (ADAs) against AZD0171 and/or durvalumab in serum
timeFrame: Up to Day 90 post last dose of study intervention on Day 15
measure: The PK profile of AZD0171, durvalumab and chemotherapy- Maximum observed plasma concentration (Cmax)
timeFrame: At predefined intervals from first dose of study intervention up to Day 90 post last dose of study intervention on Day 15
measure: The PK profile of AZD0171, durvalumab and chemotherapy - Area under the concentration-time curve (AUC)
timeFrame: At predefined intervals from first dose of study intervention up to Day 90 post last dose of study intervention on Day 15
measure: The PK profile of AZD0171, durvalumab and chemotherapy - Clearance (CL)
timeFrame: At predefined intervals from first dose of study intervention up to Day 90 post last dose of study intervention on Day 15
measure: The PK profile of AZD0171, durvalumab and chemotherapy - Terminal elimination half-life (t1/2)
timeFrame: At predefined intervals from first dose of study intervention up to Day 90 post last dose of study intervention on Day 15
measure: Participants with changes from Baseline in cluster of differentiation 8 (CD8+) T cell tumour infiltration in tumour samples
timeFrame: Up to 24 months
measure: Change from baseline in leukaemia inhibitory factor (LIF) bound to AZD0171 (total LIF)
timeFrame: At predefined intervals from first dose of study intervention up to Cycle 11 (each cycle is 28 days in length)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Ventura
country: United States
facility: Research Site
state: California
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Coeur d'Alene
country: United States
facility: Research Site
state: Idaho
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Grand Rapids
country: United States
facility: Research Site
state: Michigan
city: Buffalo
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Portland
country: United States
facility: Research Site
state: Oregon
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Madison
country: United States
facility: Research Site
state: Wisconsin
city: Barrie
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seongnam-Si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Badalona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
Study officials:
References: