A Phase I, Multicenter, Open-label, First-in-Human, Dose Escalation and Expansion Study of AZD9592 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumors

Study Identifier:
D9350C00001
CT.gov Identifier:
NCT05647122
EudraCT Identifier:
202250000000
EU Trial (CTIS) Number:
2022-501570-18-00
Study Contact Information:
N/A
Recruiting

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Study Summary

To evaluate the safety, tolerability, preliminary efficacy, pharmacokinetics (PK), pharmacodynamics, anti-tumor activity, and immunogenicity of AZD9592, as monotherapy or in combination with anti-cancer agents in patients with advanced solid tumors.

Module 1 will evaluate AZD9592 monotherapy in pts with metastatic NSCLC (mNSCLC) with EGFRm (sensitizing L858R mutation or exon 19 deletions) or EGFR wild-type, or recurrent or metastatic HNSCC.

Module 2 will evaluate AZD9592 in combination with osimertinib in pts with EGFRm mNSCLC.

To evaluate AZD9592 monotherapy in patients with metastatic NSCLC (mNSCLC) with EGFR mutations (EGFRm; sensitising L858R mutation or exon 19 deletions) or EGFR wild-type, or recurrent or metastatic HNSCC.

To evaluate AZD9592 in combination with osimertinib in patients with EGFRm mNSCLC. Each module will include dose escalation (Part A) and dose expansion (Part B) cohorts.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
  • Non-Small Cell Lung Cancer
  • Head & Neck
  • Bowel (Colorectal)
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Module 1 AZD9592 Monotherapy
    • Read More
  • Drug: Experimental: Module 2 AZD9592 Combination with Osimertinib
  • Drug: Drug: Osimertinib
  • Drug: Experimental: Module 3 AZD9592 Combination 5-FU, Bevacizumab, Leucovorin
  • Drug: Part A aims to determine the safety, tolerability and/or recommended phase 2 dose (RP2D) of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC) Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC)
  • Drug: Drug: AZD9592
  • Drug: ASCO 2023
  • Drug: experimental drug
  • Drug: 2Chinese common name: Osimertinib mesylate
  • Drug: ; Module 1 AZD9592 Monotherapy Drug: AZD9592 Varying doses of AZD9592 Module 2 AZD9592 Combination with Osimertinib Drug: AZD9592 Varying doses of AZD9592 Drug: Osimertinib tablets administered orally Module 3 AZD9592 Combination 5-FU, Bevacizumab, Leucovorin Module 3 has two parts: Part A aims to determine the safety, tolerability and/or recommended phase 2 dose (RP2D) of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC) Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC)
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • Age 18 years or more - Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-1 - Life expectancy 12 weeks or more - Measurable disease per RECIST v1.1 - Adequate organ and marrow function as defined in the protocol Additional Inclusion Criteria for Module 1: - Histologically or cytologically confirmed metastatic or locally advanced EGFRmut., NSCLC; metastatic EGFRwt. NSCLC; recurrent or metastatic HNSCC of the oral cavity; metastatic CRC. Additional Inclusion Criteria for Module 2: - Histologically or cytologically confirmed metastatic NSCLC EGFRmut. Additional Inclusion Criteria for Module 3: - Histologically or cytologically confirmed metastatic CRC.
    • • Histologically or cytologically confirmed metastatic or locally advanced EGFRmut., NSCLC; metastatic EGFRwt. NSCLC; recurrent or metastatic HNSCC of the oral cavity; metastatic CRC.
    • Additional Inclusion Criteria for Module 2:
    • • Histologically or cytologically confirmed metastatic NSCLC EGFRmut.
    • Additional Inclusion Criteria for Module 3:
    • • Histologically or cytologically confirmed metastatic CRC.
    • Able to provide signed informed consent, including compliance with the requirements and restrictions listed in the ICF and protocol
    • 2 Agrees to provide adequate baseline tumor samples prior to initiation of treatment, according to study module specific criteria
    • 3 Patients must be ≥ 18 years of age at the time of signing the informed consent
    • 4 ECOG performance status score is 0-1.
    • 5 Expected survival time≥ 12 weeks.
    • 6 Lesion measurability assessed according to RECIST v1.1 is defined as at least 1 lesion at baseline that can be accurately measured by CT or MRI, with a maximum diameter of ≥ 10 mm (lymph nodes must be ≥ 15 mm in their short axis) and suitable for accurate repeat measurements. Lesions that have received prior radiotherapy or lesions within the radiation field should not be used as target lesions unless it is confirmed that the lesion has clearly progressed on the disease
    • 7 Organs and bone marrow function normally
    • 8 The method of contraception used by men or women should comply with local regulations regarding contraceptive methods in clinical study subjects
    • 9 Patient is willing and able to comply with the study protocol for the duration of the study, including receiving treatment, attending scheduled visits, and examinations
    • 10 Histologically or cytologically confirmed diagnosis of locally advanced or metastatic EGFR-mutant NSCLC harboring one of two common EGFR mutations known to be associated with EGFR-TKI susceptibility (ex19 del/L858R). Disease progression must occur during or after treatment with a third-generation EGFR TKI, and no more than 3 lines of systemic therapy for metastatic disease must be used.
    • 11 Histologically confirmed diagnosis of recurrent or metastatic HNSCC in the oral, oropharynx, hypopharynx, or larynx. Disease progression after at least 1 prior therapy, and no more than 2 prior systemic therapies for locally advanced/metastatic HNSCC
    • 12 Histologically or cytologically confirmed diagnosis of metastatic EGFR wild-type NSCLC, prior treatment with platinum-based chemotherapy with or without PD(L)-1 inhibitors, but the number of prior systemic therapy lines for metastatic disease does not exceed 2.
    Exclusion criteria
    • 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.
    • Spinal cord compression or a history of leptomeningeal carcinomatosis.
    • Active infection including tuberculosis and HBV, HCV or HIV
    • Brain metastases unless treated (prior treatment required only for Module 1), 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 treatment.
    • Participants with cardiac comorbidities as defined in the study protocol
    • Key exclusion criteria for both modules include unresolved toxicities of Grade ≥2 (NCI CTCAE v5.0) from prior therapy, uncontrolled intercurrent illness, cardiovascular disorders, history of drug-induced interstitial lung disease or pneumonitis, and previous treatment with a TOP1i ADC or an EGFR- or MET-targeted ADC
    • Patients with cancer-related spinal cord compression or a history of leptomeningeal cancer metastasis
    • 2Patients with symptomatic brain metastases
    • 3≥2NCI CTCAE v5.0
    • 4Has an uncontrolled intercurrent illness within the past 12 months, including, but not limited to, substance abuse, severe chronic gastrointestinal illness associated with diarrhea, or psychiatric illness/social situations that limit compliance with study requirements, have a significantly increased risk of developing AEs, or affect the patient's ability to provide written informed consent.
    • 5Active or uncontrolled cardiovascular disease
    • 6Has a history of drug-induced non-infectious interstitial lung disease/non-infectious pneumonitis (requiring oral or intravenous steroids). Patients with a history of radiation pneumonitis who have recovered clinically and radiographically and do not require steroid treatment may be eligible for the study.
    • 7Presence of active infection, including tuberculosis and HBV infection, HCV, or HIV
    • 8Has a history of primary malignancy
    • 9Prior/concomitant therapy is not in compliance with protocol
    • 10Concurrent enrollment in another clinical study, unless the study is an observational (non-interventional) clinical study, or is in the follow-up period of an interventional study.
    • 11Patients with known allergies to any of the excipients of the study intervention or product.
    • 12Patients who, in the judgment of the investigator, are unlikely to comply with study procedures, restrictions, and requirements must not participate in this study.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Victor Moreno Garcia
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Non-Small Cell Lung Cancer
    Head & Neck
    Bowel (Colorectal)