First Time in Human Study of AZD8701 With or Without Durvalumab in Participants With Advanced Solid Tumours

NCT04504669 | Completed Phase 1 FDA Drug

• 3 other identifiers: D9950C00001045046692019-004539-22
• Study Type: interventional
• Target: 60
• Locations: 4 countries
• Sites: 13

Brief 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

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; Melanoma; Cervical Cancer; Advanced Solid Tumours

Keywords

Solid Tumours; Durvalumab; MEDI4736; AZD8701; Non Small cell Lung cancer; ccRenal Cancer; TNBC; first time in human; PD-L1; T regulatory cells; FOXP3

Outcome Measures

Primary Outcomes (5)

• 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

  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)

  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

  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

  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

  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

  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

  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

  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

  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

  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)

Study Arms (2)

Monotherapy

EXPERIMENTAL

Participants will receive AZD8701 intravenously, on Day 1, 3, 5 and 8 and then weekly for a maximum of 2 years.

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.

Drug: AZD8701; Biological: Durvalumab

Interventions

AZD8701 DRUG

FOXP3 antisense oligonucleotide

Combination Therapy; Monotherapy

Durvalumab BIOLOGICAL

anti PDL-1 monoclonal antibody

Also known as: MEDI4736

Combination Therapy

Eligibility Criteria

• Age: 18 Years - 101 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (13)

Research Site

Baltimore, Maryland, 21287, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Huntersville, North Carolina, 28078, United States

Location

Research Site

Franklin, Tennessee, 37067, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Madison, Wisconsin, 53792, United States

Location

Research Site

Toronto, Ontario, M5G 2M9, Canada

Location

Research Site

Rennes, 35000, France

Location

Research Site

Villejuif, 94805, France

Location

Research Site

Barcelona, 08035, Spain

Location

Research Site

L'Hospitalet de Llobregat, 08907, Spain

Location

Research Site

Madrid, 28027, Spain

Location

Research Site

Madrid, 28041, Spain

Location

Related Publications (1)

• 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.

  PMID: 35387780 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Small Cell Lung Carcinoma; Melanoma; Uterine Cervical Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Genital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: August 7, 2020
• Study Start: August 18, 2020
• Primary Completion: October 7, 2024
• Study Completion: October 7, 2024
• Last Updated: November 5, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• 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 rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified 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.

Locations

US (6); CA (1); FR (2); ES (4)