Phase I/IIa Study of AZD5335 as Monotherapy and Combination Therapy in Participants With Solid Tumors
FONTANA
A Modular Phase I/IIa, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Ascending Doses of AZD5335 Monotherapy and in Combination With Anti-cancer Agents in Participants With Solid Tumors
2 other identifiers
interventional
506
12 countries
60
Brief Summary
This research is designed to determine if experimental treatment with Antibody-drug conjugate, AZD5335, alone, or in combination with anti-cancer agents is safe, tolerable, and has anti-cancer activity in patients with advanced tumors
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 ovarian-cancer
Started Jun 2023
Typical duration for phase_1 ovarian-cancer
60 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 21, 2023
CompletedFirst Posted
Study publicly available on registry
April 4, 2023
CompletedStudy Start
First participant enrolled
June 5, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 6, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 6, 2028
March 2, 2026
February 1, 2026
4.6 years
February 21, 2023
February 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of participants with adverse events/serious adverse events
Number of participants with incidence of adverse events and with serious adverse events including changes from baseline in laboratory parameters, vital signs, ECGs, and physical examination.
From time of Informed Consent to 30 days post last dose.
The number of participants with dose limiting toxicity(DLT), as defined in the protocol
A DLT is defined as any ≥ Grade 3 treatment-emergent AE that occurs during the DLT evaluation period, not attributable to the underlying disease or extraneous causes (as defined in the protocol)
From the first dose of AZD5335 on Cycle 1 Day 1 up to and including the planned end of Cycle 1 (At the end of 21 days)
Secondary Outcomes (21)
Objective Response Rate (ORR)
From time of Informed Consent to progressive disease or withdrawal of consent.(approx 2 years)
Duration of Response (DoR)
From the first documented response to confirmed progression or death in the absence of disease progression.(approx 2 years)
Disease Control Rate (DCR)
From time of Informed Consent until progression.(approx 15 weeks)
Progression free Survival (PFS)
From time of first dose of AZD5335 or AZD5305 until the date of objective disease progression or death (by any cause in the absence of progression).(approx 2 years)
Overall Survival (OS)
From time of first dose of AZD5335 or AZD5305 until death due to any cause.(approx 2 years)
- +16 more secondary outcomes
Study Arms (5)
Module 1: AZD5335 Monotherapy
EXPERIMENTALAZD5335 Monotherapy
Module 2: AZD5335 + Saruparib
EXPERIMENTALAZD5335 + Saruparib
Module 3: AZD5335 + Bevacizumab
EXPERIMENTALAZD5335 + Bevacizumab
Module 4: AZD5335 + Carboplatin +/- Bevacizumab
EXPERIMENTALAZD5335 + Carboplatin +/- Bevacizumab
Module 5: AZD5335 + AZD9574
EXPERIMENTALAZD5335 + AZD9574
Interventions
IV Antibody-drug conjugate
IV Monoclonal antibody
IV Alkylating agent
Eligibility Criteria
You may qualify if:
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative. Participants who do not provide informed consent for Optional Genetic Research may still be enrolled in the study.
- Participant must be ≥ 18 years at the time of signing the informed consent.
- Willing to provide adequate archival and/or baseline tumor sample as applicable per module-specific criteria.
- For participants who have previously received targeted therapies such as ADCs, a fresh baseline biopsy will be required unless the most recent archival tissue sample was collected after receipt of such treatment.
- Eastern Cooperative Oncology Group Performance Status of 0 or 1.
- Participants with advanced solid tumors must have received prior adequate therapy in accordance with local practice for their tumor type and stage of disease, or, 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. Participants with contraindications or who refuse therapy in accordance with local practice may also be considered provided that it is documented that he/she was informed about all therapeutic options.
- Participants must have measurable disease per RECIST v1.1,
- A previously irradiated lesion can be considered a target lesion if the lesion is progressing and well defined.
- For participants who undergo biopsies at screening and/or on treatment, it is preferred though not required, that the biopsied lesion, be distinct from any target lesion used in the RECIST v1.1 evaluation.
- Life expectancy ≥ 12 weeks.
- Adequate organ and marrow function.
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- (a) Male participants: (i) Male participants who are sexually active with a female partner of childbearing potential must use a male condom (plus an additional contraceptive method) post-screening through 5 months following the last dose of study intervention. It is strongly recommended for the female partner of a male participant to also use a highly effective method of contraception throughout this period. In addition, male participants must refrain from freezing or donating sperm while on study and for 5 months following the last dose of study intervention.
- (b) Female participants: (i) Females of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study intervention and a negative urine or serum pregnancy test prior to starting their next cycle of treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- +2 more criteria
You may not qualify if:
- Patients with spinal cord compression or a history of leptomeningeal carcinomatosis.
- Patients with brain metastases unless, asymptomatic, stable, and not requiring continuous corticosteroids at a dose of \> 10 mg prednisone/day or equivalent for at least 4 weeks prior to first dose of study intervention.
- Treatment with any of the protocol defined medications, without adequate washout periods or time before the first dose of study intervention.
- Unresolved toxicities of Grade ≥ 2 (National Cancer Institute \[NCI\] CTCAE v5.0) from prior therapy (excluding vitiligo, alopecia, and endocrine disorders that are controlled with replacement hormone therapy). Participants with stable ≤ Grade 2 neuropathy are eligible.
- Active infection, including tuberculosis and infections with hepatitis B virus (HBV; verified by known positive hepatitis B surface antigen \[HBsAg\] result), hepatitis C virus (HCV) or known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA, CD4+ count ≥ 350/mm3, no history of acquired immune deficiency syndrome-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti-HIV medications (meaning there are no expected further changes in that time to the number or type of antiretroviral drugs in the regimen).
- Patients with a past or resolved HBV/HCV infection are eligible if:
- Negative for HBsAg and positive for anti-hepatitis B virus core protein (HBc) or
- Are HBsAg + with chronic HBV infection (lasting 6 months or longer) and meet conditions i-iii below:
- (i) HBV DNA viral load \<100 IU/mL. (ii) Have normal transaminase values, or, if liver metastases are present, abnormal transaminases, with a result of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \<3 x upper limit of normal (ULN), which are not attributable to HBV infection.
- (iii) Start or maintain antiviral treatment if clinically indicated as per the Investigator or as per local guideline.
- Note for Japan: Japanese patients with positive anti-HBs/anti-HBc and negative HBsAg will be assessed following local guidelines.
- (c) Participants testing positive for HCV antibody are eligible only if the polymerase chain reaction test result is negative for HCV RNA.
- Patient has ILD/pneumonitis or has a history of (non-infectious) ILD/pneumonitis that required oral or IV steroids or supplemental oxygen, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- Patients with a history of radiation pneumonitis which has clinically and radiologically resolved and not requiring treatment with steroids may be eligible.
- History of another malignancy except for:
- +25 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (60)
Research Site
Duarte, California, 91010, United States
Research Site
Irvine, California, 92618, United States
Research Site
La Jolla, California, 92093, United States
Research Site
Aurora, Colorado, 80045, United States
Research Site
Louisville, Kentucky, 40202, United States
Research Site
Boston, Massachusetts, 02114, United States
Research Site
Detroit, Michigan, 48201, United States
Research Site
Columbus, Ohio, 43201, United States
Research Site
Portland, Oregon, 97239, United States
Research Site
Providence, Rhode Island, 02903, United States
Research Site
Providence, Rhode Island, 02905, United States
Research Site
Houston, Texas, 77030, United States
Research Site
Fairfax, Virginia, 22031, United States
Research Site
Liverpool, 2170, Australia
Research Site
Melbourne, 3000, Australia
Research Site
Edmonton, Alberta, T6G 1Z2, Canada
Research Site
London, Ontario, N6A 5W9, Canada
Research Site
Toronto, Ontario, M5G 2M9, Canada
Research Site
Montreal, Quebec, H2X 0A9, Canada
Research Site
Montreal, Quebec, H4A 3J1, Canada
Research Site
Chengdu, 610041, China
Research Site
Chongqing, 400030, China
Research Site
Guangzhou, 510000, China
Research Site
Guangzhou, 510060, China
Research Site
Jinan, 250117, China
Research Site
Xi'an, 710061, China
Research Site
Zhengzhou, 450008, China
Research Site
Berlin, 13353, Germany
Research Site
Essen, 45136, Germany
Research Site
Freiburg im Breisgau, 79106, Germany
Research Site
Hanover, 30625, Germany
Research Site
Leipzig, 04103, Germany
Research Site
Mannheim, 68167, Germany
Research Site
Regensburg, 93053, Germany
Research Site
Haifa, 3109601, Israel
Research Site
Ramat Gan, 52621, Israel
Research Site
Hidaka-shi, 350-1298, Japan
Research Site
Kashiwa, 227-8577, Japan
Research Site
Kōtoku, 135-8550, Japan
Research Site
Sunto-gun, 411-8777, Japan
Research Site
Tokyo, 104-0045, Japan
Research Site
Seoul, 03080, South Korea
Research Site
Seoul, 06351, South Korea
Research Site
Barcelona, 8035, Spain
Research Site
Madrid, 28041, Spain
Research Site
Madrid, 28050, Spain
Research Site
Málaga, 29010, Spain
Research Site
Taichung, 40705, Taiwan
Research Site
Tainan, 70403, Taiwan
Research Site
Taipei, 10002, Taiwan
Research Site
Taipei, 11259, Taiwan
Research Site
Ankara, 06050, Turkey (Türkiye)
Research Site
Ankara, 06200, Turkey (Türkiye)
Research Site
Ankara, 06800, Turkey (Türkiye)
Research Site
Istanbul, 34718, Turkey (Türkiye)
Research Site
Cambridge, CB2 0XY, United Kingdom
Research Site
Glasgow, Scotland, G12 0YN, United Kingdom
Research Site
London, SE1 9RT, United Kingdom
Research Site
London, SW3 6JJ, United Kingdom
Research Site
Sutton, SM2 5PT, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Funda Meric-Bernstam, MD
UT MD Anderson Cancer Center
Central Study Contacts
AstraZeneca Clinical Study Information Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 21, 2023
First Posted
April 4, 2023
Study Start
June 5, 2023
Primary Completion (Estimated)
January 6, 2028
Study Completion (Estimated)
January 6, 2028
Last Updated
March 2, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- 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.
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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.