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Study of Inupadenant (EOS100850) With Chemotherapy as Second Line Treatment for Nonsquamous Non-small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT05403385
Recruitment Status : Recruiting
First Posted : June 3, 2022
Last Update Posted : September 21, 2023
Sponsor:
Information provided by (Responsible Party):
iTeos Therapeutics ( iTeos Belgium SA )

Tracking Information
First Submitted Date  ICMJE May 18, 2022
First Posted Date  ICMJE June 3, 2022
Last Update Posted Date September 21, 2023
Actual Study Start Date  ICMJE August 26, 2022
Estimated Primary Completion Date April 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2022)
  • Dose-finding to determine recommended Phase 2 dose [ Time Frame: At the end of Cycle 1 (each cycle is 21 days) ]
    Incidence of dose-limiting toxicities
  • Incidence of treatment-emergent adverse events [Safety and Tolerability] [ Time Frame: Duration of intervention (up to 24 months) plus 30 days follow-up ]
    Incidence of adverse events (AEs), serious adverse events, AEs leading to discontinuation, deaths, and clinically significant laboratory abnormalities.
  • Progression-free survival [Efficacy] [ Time Frame: From randomization to first-documented radiological progression or date of death from any cause, whichever comes first, assessed up to 24 months. ]
    Time from first dose to the date of first documented radiologic progression per RECIST v1.1 or time of death, which ever comes first
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2022)
  • Overall Response Rate [Efficacy] [ Time Frame: From randomization to first-documented radiological improvement, if applicable, assessed up to 24 months. ]
    Proportion of participants with a best overall response of complete (CR) or partial (PR) response as assessed by RECIST v1.1
  • Duration of Response [Efficacy] [ Time Frame: From first-documented CR or PR to first radiological progression or date of death, whichever comes first, assessed up to 24 months. ]
    Time from first CR or PR to first documented progression or death from any cause, per RECIST v1.1
  • Percent Change in Tumor Size [Efficacy] [ Time Frame: From randomization to the documented radiological assessment with the smallest tumor size sum, assessed up to 24 months. ]
    Change in sum of size of target tumors from baseline, per RECIST v1.1
  • Disease Control Rate [Efficacy] [ Time Frame: From randomization to second-documented radiological CR, PR or SD, if applicable, assessed up to 24 months. ]
    Proportion of participants with CR, PR, or stable disease (SD) sustained over at least 2 consecutive tumor assessments, per RECIST v1.1
  • Overall Survival [Efficacy] [ Time Frame: From randomization to death due to any cause, assessed up to 24 months. ]
    Time from randomization to date of death due to any cause.
  • Efficacy (Patient Reported Outcomes) [ Time Frame: Duration of intervention (up to 24 months) plus 30 days follow-up ]
    Time to definitive deterioration in global health status/quality of life
  • Peak plasma concentration (Cmax) [ Time Frame: From first dose of inupadenant through 24 hours ]
    Cmax for inupadenant and its primary metabolite as observed by assessment of concentration-time profile
  • Time to peak plasma concentration (Tmax) [ Time Frame: From first dose of inupadenant through 24 hours ]
    Tmax for inupadenant and its primary metabolite as observed by assessment of concentration-time profile
  • Plasma half-life (T-1/2) [ Time Frame: At the end of Cycle 12 (each cycle is 3 weeks) ]
    T-1/2 for inupadenant and its primary metabolite
  • Area under the concentration-time curve (AUCinf) [ Time Frame: At the end of Cycle 12 (each cycle is 3 weeks) ]
    AUC from Time 0 extrapolated to infinity for inupadenant and its primary metabolite
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Inupadenant (EOS100850) With Chemotherapy as Second Line Treatment for Nonsquamous Non-small Cell Lung Cancer
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled, Phase 2 Study Evaluating Efficacy and Safety of Inupadenant in Combination With Carboplatin and Pemetrexed in Adults With Nonsquamous Non-small Cell Lung Cancer Who Have Progressed on Immunotherapy
Brief Summary Part 1 of the study determines the optimal dose of inupadenant to be given in combination with carboplatin and pemetrexed to patients that progressed after receiving specific first line treatments for Stage 3 or metastatic non-small cell lung cancer. Part 2 compares the efficacy of inupadenant to placebo when both are combined with carboplatin and pemetrexed for patients that progressed after receiving the same first line treatments for Stage 3 or metastatic non-small cell lung cancer.
Detailed Description

In both Part 1 and Part 2, there are two nonsquamous NSCLC patient populations eligible for the study treatment: 1)patients with Stage III, non-resectable cancer that have received chemoradiotherapy, followed by durvalumab, and then have progressed; 2)patients who have received only first-line immunotherapy with anti-PD-L1 therapy, but no chemotherapy, in the metastatic setting, then progressed.

In Part 1, all participants receive open-label inupadenant with standard of care doses of carboplatin and pemetrexed. Carboplatin is given at q3week intervals for no more than 4 cycles; pemetrexed continues at q3week as prescribed by the Investigator. Inupadenant is given orally BID. Dose-limiting toxicities are monitored during the first 21 days of treatment and a modified 3+3 escalation method is utilized to determine the recommended phase 2 dose (RP2D). Imaging and safety and PRO assessments are performed during the treatment and follow-up phase. Treatment continues until progression, withdrawal of consent, start of new anti-cancer treatment, end of study, or death.

Part 2 is double-blinded, with subjects randomized 1:1 to receive the RP2D of inupadenant or matched placebo. All subjects receive the carboplatin and pemetrexed per standard of care. Imaging, safety and PRO assessments are performed during the treatment and follow-up phase. Treatment continues until progression, withdrawal of consent, start of new anti-cancer treatment, end of study, or death.

In both Parts 1 and 2, blood samples are drawn to further define the pharmacokinetic profile of inupadenant and biosamples are collected for additional exploratory analyses.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Single Group Assignment Part 1 sequential dose escalation. Part 2 randomized double-blind.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
The dose-finding part (Part 1) of this study is open-label whereas the randomized part (Part 2) is double-blinded. Therefore, for Part 2, the subject, the Investigator and Sponsor personnel or delegate(s) who are involved in the treatment administration or clinical evaluation of the subjects will be unaware of the group assignments. The chemotherapy agents administered during Part 2 will be open label.
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic NSCLC
  • Stage III NSCLC
Intervention  ICMJE
  • Drug: inupadenant
    Adenosine 2a receptor antagonist
    Other Name: EOS100850
  • Drug: Placebo
    matched placebo capsule to inupadenant
  • Drug: Carboplatin
    standard of care chemotherapeutic, alkylating agent
  • Drug: Pemetrexed
    standard of care chemotherapeutic, anti-metabolite
    Other Name: Alimta
Study Arms  ICMJE
  • Experimental: Part 1, open label
    Inupadenant will be given at one or more dose levels to determine the recommended Phase 2 dose (RP2D).
    Interventions:
    • Drug: inupadenant
    • Drug: Carboplatin
    • Drug: Pemetrexed
  • Experimental: Part 2, active treatment
    Treatment with inupadenant combined with carboplatin and pemetrexed
    Interventions:
    • Drug: inupadenant
    • Drug: Carboplatin
    • Drug: Pemetrexed
  • Placebo Comparator: Part 2, placebo
    Treatment with matched placebo combined with carboplatin and pemetrexed
    Interventions:
    • Drug: Placebo
    • Drug: Carboplatin
    • Drug: Pemetrexed
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 31, 2022)
192
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2025
Estimated Primary Completion Date April 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Confirmed diagnosis of metastatic (Stage IV) or locally advanced, unresectable (Stage III) NSCLC of nonsquamous pathology that has relapsed or progressed
  2. Measurable disease as defined by RECIST v1.1 criteria
  3. PD-L1 expression status available at or after the time of diagnosis of advanced or metastatic NSCLC disease
  4. Can provide existing biopsy taken within 2 years prior to entering trial or provide fresh biopsy
  5. Have relapsed or progressed after prior anti- PD-(L)1 therapy as follows:

    1. At least 12 weeks of treatment with only 1 line of anti-PD-(L)1 therapy (mono or combo) in the metastatic setting, without concomitant chemotherapy OR
    2. At least 12 weeks of single-agent durvalumab
  6. Adequate organ function
  7. ECOG performance status of 0 to 1.

Exclusion Criteria:

  1. Symptomatic and/or untreated central nervous system (CNS) metastases or leptomeningeal disease.
  2. Presence of active second malignancy
  3. EGFR or ALK mutation. Participants with presence of other driver mutations are allowed if targeted therapy is not available as per local standard of care.
  4. Preexisting gastrointestinal disorders/conditions that may interfere with ingestion or absorption of oral medications.
  5. History of or active (non-infectious) pneumonitis/ interstitial disease or lung fibrosis, except for Grade 1 pneumonitis from prior chemoradiation therapy (Stage III patients).
  6. History of or active autoimmune disease requiring systemic treatment in the last 6 months or persistent immune-mediated toxicity caused by checkpoint inhibitor therapy > Grade 2
  7. Known active or chronic hepatitis B or C infection unless adequately treated for at least 4 weeks with no detectable viral load; known infection with human immunodeficiency virus (HIV) unless receiving antiretroviral therapy with well-controlled disease.
  8. History of life-threatening toxicity related to prior immune therapy or any toxicity resulting in permanent discontinuation from prior therapy.
  9. Diagnosis of immunodeficiency or any condition requiring concurrent use of systemic immunosuppressants or corticosteroids.
  10. Active infection requiring systemic therapy ≤ 7 days prior to first dose of study treatment.
  11. Any other oncologic treatments administered ≤14 days (<28 days in case of checkpoint inhibitor therapy) prior to first dose of study treatment. Also, ongoing adverse effects from such treatment > Grade 1 with the exception for alopecia and Grade 2 peripheral neuropathy.
  12. Non-study related minor surgical procedure ≤7 days, or major surgical procedure of ≤ 5 weeks prior to first dose of study treatment.
  13. Uncontrolled or significant cardiovascular disease
  14. History of allergy or hypersensitivity to any of the study treatments.
  15. Treatment with a live or live attenuated vaccine.
  16. Treatment with moderate or strong inducers or inhibitor of CYP 3A4, inhibitors of P-glycoprotein, or substrates of breast cancer resistance protein
  17. Pregnant or breast-feeding
  18. Male and Female participants: Lack of agreement to use highly effective method of contraception during treatment and for 6 months after the last administration of chemotherapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical Monitor +32 71 91 99 33 clinical_info@iteostherapeutics.com
Listed Location Countries  ICMJE Belgium,   Canada,   Czechia,   France,   Italy,   Poland,   Spain,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05403385
Other Study ID Numbers  ICMJE A2A-005
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party iTeos Therapeutics ( iTeos Belgium SA )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE iTeos Belgium SA
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account iTeos Therapeutics
Verification Date September 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP