Study of AZD2811 + Durvalumab in ES-SCLC (TAZMAN)

A Phase II Multicenter, Open-Label, Single Arm Study to Determine the Efficacy, Safety and Tolerability of AZD2811 and Durvalumab Combination as Maintenance Therapy After Induction With Platinum-Based Chemotherapy Combined With Durvalumab, for the First-Line Treatment of Patients With Extensive Stage Small-Cell Lung Cancer

A Phase II Multicenter, Open-Label, Single Arm Study to Determine the Efficacy, Safety and Tolerability of AZD2811 and Durvalumab Combination as Maintenance Therapy After Induction with Platinum-Based Chemotherapy Combined with Durvalumab, for the First-Line Treatment of Patients with Extensive Stage Small-Cell Lung Cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Small-Cell Lung Cancer
• Intervention / Treatment: Drug: Durvalumab; Drug: AZD2811; Drug: Carboplatin; Drug: Cisplatin; Drug: Etoposide

Detailed Description

Primary objective of this study is to evaluate the efficacy of AZD2811 and durvalumab in patients who have not progressed following induction therapy with platinum-based chemotherapy combined with durvalumab.

This is an open-label, single arm study. Patients will be treated in an induction phase with platinum-based induction therapy and durvalumab. At the end of this induction period, participants will be assessed for disease progression, per RECIST v1.1.

Participants who have not progressed per RECIST v1.1 at the end of the induction phase will roll over into the maintenance phase of the trial, where patients will commence AZD2811 and durvalumab combination.

Participants will be treated with AZD2811 and durvalumab as maintenance therapy until confirmed progressive disease, start of non-protocol defined anticancer therapy, unacceptable toxicity, or withdrawal of consent.

If study intervention is permanently discontinued, the participant will remain in the study to be evaluated for safety assessment, as well as for confirmed disease progression and for survival.

Targeted population are adult patients (aged ≥18 years) with histologically or cytologically documented extensive disease (American Joint Committee on Cancer Stage (7th edition) IV SCLC [T any, N any,M1 a/b]), or T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan. Patients must have WHO/ECOG performance status of 0 or 1.

Tumor assessments will be performed at Screening as baseline with follow-up every 6 weeks ± 1 week for the first 36 weeks, and then every 8 weeks ±1 week until confirmed objective disease progression.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Cheongju-si, Korea, Republic of, 28644
    • Research Site
  • Jinju-si, Korea, Republic of, 52727
    • Research Site
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 06591
    • Research Site
  • Seoul, Korea, Republic of, 6351
    • Research Site
  • Seoul, Korea, Republic of, 138-736
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-796
    • Research Site
  • Olsztyn, Poland, 10-357
    • Research Site
  • Poznan, Poland, 60-693
    • Research Site
• Spain
  • Sevilla, Spain, 41071
    • Research Site
  • Valencia, Spain, 46015
    • Research Site
• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 128 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented evidence of extensive stage SCLC (ES-SCLC)
• Participants must be considered suitable to receive an induction platinum-based chemotherapy regimen, combined with durvalumab, as first-line treatment for ES-SCLC
• No prior exposure to immune-mediated therapy
• Life expectancy ≥12 weeks at Day 1.
• ECOG 0 or 1 at enrolment.

Exclusion Criteria:

• Any history of radiotherapy to the chest prior to systemic therapy or planned consolidation chest radiation therapy
• Has a paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic treatment (systemic steroids or immunosuppressive agents) or has a clinical symptomatology suggesting worsening of PNS
• Active infection including tuberculosis, HIV, hepatitis B and C
• Active or prior documented autoimmune or inflammatory disorders
• Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: AZD2811 + Durvalumab; Induction: Durvalumab + Platinum Chemotherapy (Carboplatin or cisplatin & Etoposide) Maintenance: AZD2811 + Durvalumab

Drug: Durvalumab; IV infusions through induction phase. IV infusions through maintenance phase until PD or other discontinuation criteria.; Other Names: Imfinzi; Drug: AZD2811; IV infusions through maintenance phase until PD or other discontinuation criteria.; Drug: Carboplatin; IV infusions through induction phase if chosen by Investigator.; Drug: Cisplatin; IV infusions through induction phase if chosen by Investigator.; Drug: Etoposide; IV infusions through induction phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maintenance participants alive and progression free (APF12) per RECIST 1.1 [Efficacy]	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance participants alive at 12 months (OS12), 15 months (OS15), and 18 months (OS18)		Up to 18 months
Maintenance participants alive and progression free at 6 months (APF6) and 9 months (APF9) using investigator assessments according to RECIST 1.1		Up to 9 months
Objective response rate (ORR) for all participants using investigator assessments according to RECIST 1.1		Approximately 3 years
Maintenance participants Progression-free survival (PFS) using investigator assessments according to RECIST 1.1		Approximately 3 years
Overall survival (OS) in maintenance participants		Approximately 3 years
Assess safety and tolerability profile in terms safety assessments, adverse events per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event [CTCAE] v5.0, and dose modifications	Incidence of adverse events as measured by CTCAE 5.0	Approximately 3 years
Cmin of durvalumab		Predose Maintenance Day 1 of Cycles 5 and 7 (up to approximately 3 years)
Cmax of durvalumab		Predose Maintenance Day 1 of Cycles 5 and 7 (up to approximately 3 years)
AZD2811 PK: Pharmacokinetics of AZD2811 and its metabolites by measuring whole blood concentration		Approximately 3 years
EORTC 30: Health related quality of life based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire - Cancer (QLQ-C30) v3.0.	The EORTC QLQ-C30 consists of 30 questions that can be combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 6 individual items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global measure of health status. The EORTC QLQ-C30 will be scored according to the EORTC QLQ-C30 Scoring Manual. Quality of life issues are assessed using a four-point scale (1= not at all, 2 = a little, 3 = quite a bit, 4 = very much), apart from two questions which are measured between 1 (Very Poor) to 7 (Excellent).	Approximately 3 years
EORTC 13: Lung cancer specific quality of life based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire - Lung Cancer (QLQ-LC13) v1.0.	The EORTC QLQ-LC13 is a 13-item questionnaire comprised of 1 symptom scale assessing dysponea, and a series of single questions assessing cough, haemoptysis, sore mouth, dysphagis, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, and use of pain medication. All items are assessed using a Likert four-point scale (1= not at all to 4 = very much). Scoring will be done according to the EORTC QLQ-C30 Scoring Manual (Fayers et al., 2001). A high score for a symptom scale or single item represents a high level of symptomology or problems.	Approximately 3 years

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2021
• Primary Completion (Actual): June 18, 2022
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: December 16, 2020
• First Submitted That Met QC Criteria: February 8, 2021
• First Posted (Actual): February 9, 2021

Study Record Updates

• Last Update Posted (Estimate): December 15, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Small Cell Lung Cancer; ES-SCLC; SCLC; Extensive Stage Small-Cell Lung Cancer; Carcinoma, Small Cell Lung; Oat Cell Carcinoma of Lung; Oat Cell Lung Cancer; Small Cell Cancer Of The Lung
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Carboplatin; Etoposide; Cisplatin; Durvalumab
• Other Study ID Numbers: D6132C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: 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.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No