Clinical trial NCT05123482: A Phase I/IIa Study of AZD8205 Given Alone or in Combination With Anticancer Drugs, in Participants With Advanced or Metastatic Solid Malignancies
Official title: A Phase I/IIa Multi-center, Open-label Master Protocol Dose Escalation and Expansion Study of AZD8205 as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Solid Tumors (BLUESTAR)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Biliary Tract Carcinoma
Ovarian Cancer
Endometrial Cancer
Squamous Non-Small Cell Lung Cancer
Keywords: First In Human, antibody drug conjugate, cancer, solid tumour, Phase I, Phase IIa
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-11-17
Enrollment: 370
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study consists a master protocol with sub studies each evaluating the safety and tolerability of AZD8205 dosed as monotherapy, or in Combination with Anticancer Agents in Participants with Advanced Solid Tumours:

Sub Study 1 (AZD8205 monotherapy)

* Part A Dose Escalation
* Part B Dose Expansion

Sub Study 2 (AZD8205 in combination with rilvegostomig)

* Part A Dose Escalation
* Part B Dose Expansion

Sub Study 3 (AZD8205 in combination with saruparib with or without rilvegostomig)

* Part A Dose Escalation
* Part B Dose Expansion
Primary purpose: TREATMENT

Brief summary: This research study is studying a new compound, AZD8205, as a possible treatment for advanced or metastatic solid tumours alone or in combination with anti-cancer agents

Detailed description: This study is a Phase I/IIa Multi-center, Open-label Master Protocol Dose Escalation and Expansion Study of AZD8205 as Monotherapy and in Combination with Anticancer Agents in Participants with Advanced Solid Tumors

Eligibility criteria: Key Inclusion Criteria:

* Age ≥ 18 years
* Relapsed/metastatic solid tumors treated with prior adequate standard of care therapy for tumor type and stage of disease or where in the opinion of the Investigator, a clinical trial is the best option for the next treatment based on response and/or tolerability to prior therapy.
* Measurable disease per RECIST v1.1
* Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-1
* Life expectancy ≥ 12 weeks
* Adequate bone marrow, hepatic, and renal function as defined in the protocol

Additional Inclusion Criteria For Sub-Study 1 Part A:

• Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC or endometrial cancer

Additional Inclusion Criteria For Sub-Study 1 Part B:

* Histologically or cytologically confirmed metastatic or locally advanced and recurrent disease for the respective cohort:

  1. Cohort B1 (Biliary Tract Cancer)
  2. Cohort B2 (Ovarian Cancer)
  3. Cohort B3 (Breast Cancer)
  4. Cohort B4 (Endometrial Cancer)
  5. Cohort B5 (Squamous Non-Small Cell Lung Cancer)

     Additional Inclusion Criteria For Sub-Study 2 Part A:
* Minimum body weight ≥ 30 kg.
* Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC, endometrial cancer or squamous non-small cell lung cancer.

Additional Inclusion Criteria For Sub-Study 3 Part A:

* Minimum body weight ≥ 30 kg (for participants enrolled in cohorts including rilvegostomig only).
* Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC, endometrial cancer or squamous non-small cell lung cancer.

Key Exclusion Criteria:

* Treatment with any of the following:

  1. Nitrosourea or mitomycin C within 6 weeks prior to the first dose of study treatment
  2. Any investigational agents or study drugs from a previous clinical study within 5 half-lives or 28 days (whichever is shorter) prior to the first dose of study treatment
  3. Any other anticancer treatment within the following time periods prior to the first dose of study intervention:

     1. Cytotoxic treatment: 21 days
     2. Non-cytotoxic drugs: 21 days or 5 half-lives (whichever is shorter)
     3. Biological products including immuno-oncology agents: 28 days
* Spinal cord compression or a history of leptomeningeal carcinomatosis.
* Brain metastases unless treated, asymptomatic, stable, and not requiring continuous corticosteroids at a dose of \> 10 mg prednisone/day or equivalent for at least 4 weeks prior to start of study.
* Active infection including tuberculosis and HBV, HCV or HIV
* History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
* Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
* Participants with any of the following cardiac criteria:

  1. History of arrhythmia which is symptomatic or requires treatment (NCI CTCAE v5.0 Grade 3); symptomatic or uncontrolled atrial fibrillation, or asymptomatic sustained ventricular tachycardia.
  2. Uncontrolled hypertension.
  3. Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention, or coronary artery bypass grafting within 6 months.
  4. History of brain perfusion problems (eg, carotid stenosis) or stroke, or transient ischemic attack in the last 6 months prior to screening.
  5. Symptomatic heart failure (NYHA class ≥ 2).
  6. Prior or current cardiomyopathy.
  7. Severe valvular heart disease.
  8. Mean resting QTcF \> 470 msec.
  9. Risk factors for QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age.

Additional Exclusion Criteria For Sub-Study 2 Part A:

* Thromboembolic event within 3 months before the first dose of study intervention - No longer applicable per amendment 7
* Experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
* Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
* History of organ transplant

Additional Exclusion Criteria For Sub-Study 3 Part A:

* Concomitant use of medications or herbal supplements known to be strong cytochrome P (CYP) 3A4 inducers/inhibitors.
* Any history of persisting (\> 2 weeks) severe cytopenia due to any cause
* Patients with any known predisposition to bleeding
* Patients with history of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML (as determined by prior diagnostic investigation).
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of saruparib.

Primary outcomes:
measure: The number of patients with adverse events
timeFrame: From time of Informed consent to 30 days post last dose (approximately 1 year).
measure: The number of patients with serious adverse events
timeFrame: From time of Informed consent to 30 days post last dose (approximately 1 year)
measure: The number of patients with dose-limiting toxicity (DLT), as defined in the protocol.
timeFrame: From first dose of study treatment until the end of Cycle 1 (approximately 21 days).
measure: The number of patients with changes from baseline laboratory findings, ECGs and vital signs
timeFrame: From time of informed consent to 30 days post last dose (approximately 1 year)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years )
measure: Duration of response (DoR)
timeFrame: From the first documented response to confirmed progressive disease or death ( approx. 2 years )
measure: Progression free Survival (PFS)
timeFrame: From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years )
measure: Disease Control Rate at 12 weeks (DCR-12)
timeFrame: Measured from first dose until progression. For each patient, this is expected to be at 12 weeks
measure: Overall Survival (OS)
timeFrame: From first dose of AZD8205 to death ( approx. 2 years )
measure: Pharmacokinetics of AZD8205: Area Under the concentration-time curve (AUC)
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
measure: Pharmacokinetics of AZD8205: Maximum plasma concentration of the study drug (Cmax)
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
measure: Pharmacokinetics of AZD8205: Time to maximum plasma concentration of the study drug (T-max)
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
measure: Pharmacokinetics of AZD8205: Clearance
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
measure: Pharmacokinetics of AZD8205: Terminal elimination half-life (t 1/2)
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
measure: Immunogenicity of AZD8205.
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
measure: Sub Study 1: AZD8205 monotherapy Pharmacodynamics
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
measure: Sub Study 2: AZD8205 in combination with rilvegostomig Pharmacodynamics
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
measure: Sub-study 2: Rilvegostomig Pharmacokinetics when in combination with AZD8205
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years)
measure: Sub-study 2: Immunogenicity of Rilvegostomig when in combination with AZD8205
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years)
measure: Sub-Study 3: Pharmacokinetics of saruparib in combination with AZD8205 with or without rilvegostomig
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years)
measure: Sub-study 3: Pharmacokinetics of rilvegostomig in combination with AZD8205 and saruparib
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years)
measure: Sub-Study 3: Immunogenicity of rilvegostomig in combination with AZD8205 and saruparib
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Research Site
state: California
city: Irvine
country: United States
facility: Research Site
state: California
city: Santa Monica
country: United States
facility: Research Site
state: California
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Sarasota
country: United States
facility: Research Site
state: Florida
city: Shreveport
country: United States
facility: Research Site
state: Louisiana
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Commack
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Houston
country: United States
facility: Research Site
state: Texas
city: Clayton
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: Nedlands
country: Australia
facility: Research Site
city: South Brisbane
country: Australia
facility: Research Site
city: Anderlecht
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Beijing
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Shandong
country: China
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Modena
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Hidaka-shi
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Kurume-shi
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
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: Amsterdam
country: Netherlands
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Cardiff
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
References:
citation: Kinneer K, Wortmann P, Cooper ZA, Dickinson NJ, Masterson L, Cailleau T, Hutchinson I, Vijayakrishnan B, McFarlane M, Ball K, Davies M, Lewis A, Huang Y, Rosenbaum AI, Yuan J, Chesebrough J, Anderton J, Monks N, Novick S, Wang J, Dimasi N, Christie RJ, Sabol D, Tosto FA, Wallez Y, Leo E, Albertella MR, Staniszewska AD, Tice DA, Howard PW, Luheshi N, Sapra P. Design and Preclinical Evaluation of a Novel B7-H4-Directed Antibody-Drug Conjugate, AZD8205, Alone and in Combination with the PARP1-Selective Inhibitor AZD5305. Clin Cancer Res. 2023 Mar 14;29(6):1086-1101. doi: 10.1158/1078-0432.CCR-22-2630.