Clinical Trial - NCT02108964

A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies

Active, not recruiting

Sponsor: Novartis Pharmaceuticals

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02108964

Protocol Info

Short Description: Phase I/II Study of EGFRmut-TKI EGF816 in EGFRmut Solid Malignancies
Long Description: A Phase I/II, Multicenter, Open-Label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients with EGFRmut Solid Malignancies
MGH Status: Closed
Sponsor: Novartis
Disease Program: Thoracic

Next Steps


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Purpose

To estimate the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) (Phase l part) of EGF816 and to investigate the anti-tumor activity of EGF816 (Phase II part).
Condition Title Intervention Phase
Advanced Non-small Cell Lung Cancer EGF816 Phase 1/Phase 2
Study Type Interventional
Official Title A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies

Primary Outcome Measures

Incidence of Dose Limiting Toxicity (DLT) Phase I Part [Time Frame: First 28 days of dosing] [Designated as safety issue: ]

Overall Response Rate (ORR) Phase II Part [Time Frame: At least 24 weeks] [Designated as safety issue: ]


Secondary Outcome Measures

Progression-free survival (Phase I & Phase II Parts) [Time Frame: At least 24 weeks] [Designated as safety issue: ]

Duration of Response (Phase I & II Parts) [Time Frame: At least 24 weeks] [Designated as safety issue: ]

Plasma concentration vs. time profiles, plasma PK parameters (Phase I Part & Phase II part) [Time Frame: 12 weeks (Cycle 1 Day 1,2,8, 15; Cycle 2 Day 1, 2; Cycle 3 Day 1; Cycle 4 Day 1] [Designated as safety issue: ]

Pre- and on-treatment immunohistochemistry of EGFR pathway molecules (prior to PA05) [Time Frame: 15 days (Pre-screening, screening and Cycle 1 Day 15)] [Designated as safety issue: ]

Overall Response Rate (Phase I & II Parts) [Time Frame: At least 24 weeks] [Designated as safety issue: ]

Disease Control Rate (Phase I & II Parts) [Time Frame: At least 24 weeks] [Designated as safety issue: ]

Time to Response (Phase I & II Parts) [Time Frame: At least 24 weeks] [Designated as safety issue: ]

Safety: Incidence and severity of AEs, changes in laboratory values, vital signs & ECGs. Tolerability: Dose interruptions & reductions (Phase I & II Parts) [Time Frame: At least 24 weeks] [Designated as safety issue: ]

Duration of Response (Phase II Part) [Time Frame: At least 24 weeks] [Designated as safety issue: ]

Disease Control Rate (Phase II Part) [Time Frame: At least 24 weeks] [Designated as safety issue: ]

Progression-Free Survival (Phase II Part) [Time Frame: At least 24 weeks] [Designated as safety issue: ]

Time to Response (Phase II Part) [Time Frame: At least 24 weeks] [Designated as safety issue: ]

Overall Survival (Phase II Part) [Time Frame: At least 24 weeks] [Designated as safety issue: ]

Estimated Enrollment: 225
Study Start Date: June 2014
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: March 2018
Arms Assigned Interventions

Experimental:Phase I part

180 patients with EGFR mutations (Recruitment is completed)
Drug:EGF816
EGF816 will be dosed once daily. On the first day of each treatment Cycle, the patient receives an adequate drug supply for self-administration at home. The investigator must emphasize compliance with the study treatment and will instruct the patient to take EGF816 exactly as prescribed.

Experimental:Phase II part

At least 40 patients who have advanced NSCLC and EGFR activating mutations (i.e. L858R and/or ex19del). These patients must be treatment naïve and must have not received any systemic antineoplastic therapy for advanced NSCLC. Note: patients who have received no more than 1 cycle of antineoplastic therapy in the advanced setting are allowed.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria: (For all patients unless otherwise specified)

  • Histologically or cytologically confirmed locally advanced (stage IIIB not amenable to definitive multi-modality therapy including surgery) or metastatic (stage IV) EGFR mutant NSCLC.
  • Patients with controlled brain metastases
  • ECOG performance status: Phase I part: 0, 1, or 2; Phase II part: 0 or 1
  • Presence of at least one measurable lesion according to RECIST 1.1
  • Patients who are either HBsAg positive or HBV-DNA positive must be willing and able to take antiviral therapy 1-2 weeks prior to 1st dose of EGF816 treatment and continue on antiviral therapy for at least 4 weeks after the last dose of EGF816
  • Patients must have negative hepatitis C antibody (HCV-Ab) or positive HCV-Ab but undetectable level of HCV-RNA. Note: patients with detectable HCV-RNA are not eligible for the study.
  • For Phase I: patients must have failed no more than 3 lines of any systemic antineoplastic therapy for advanced NSCLC, including EGFR-TKI
  • For Phase II: patients must be naïve from any systemic antineoplastic therapy in the advanced setting. Patients who have failed no more than 1 cycle of systemic antineoplastic therapy in the advanced setting are allowed.

Exclusion criteria: (Applies to all patients unless otherwise specified)

  • Patients with a history or presence of ILD or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention)
  • Presence or history of another malignancy
  • Undergone a bone marrow or solid organ transplant
  • Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory)
  • Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use at the time of study entry except for control of brain metastases, topical applications, inhaled sprays, eye drops or local injections
  • Patients with clinically significant, uncontrolled heart disease
  • Any prior therapies ≤ 4 weeks prior to the first dose of study treatment
  • Patients who are receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5 and cannot be discontinued 1 week prior to the start of EGF816 treatment and for the duration of the study.
  • Patients who have impairment of GI function or GI disease that may significantly alter the absorption of EGF816 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome)
  • Patients who are receiving treatment with any enzyme-inducing anticonvulsant that cannot be discontinued at least 1 week before first dose of study treatment, and for the duration of the study
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception
  • Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after stopping treatment Other protocol-defined inclusion and exclusion criteria may apply.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02108964

Locations

  • United States, Massachusetts
    • Massachusetts General Hospital Mass General Boston, Massachusetts, United States, 02114
  • United States, New York
    • Memorial Sloan Kettering Oncology Department New York, New York, United States, 10017
  • Canada, Ontario
    • Novartis Investigative Site Toronto, Ontario, Canada, M5G 2M9
  • Germany, Nordrhein-Westfalen
    • Novartis Investigative Site Koeln, Nordrhein-Westfalen, Germany, 50937
  • Germany,
    • Novartis Investigative Site Berlin, , Germany, 13125
  • Italy, MI
    • Novartis Investigative Site Milano, MI, Italy, 20133
  • Japan, Aichi
    • Novartis Investigative Site Nagoya, Aichi, Japan, 464 8681
  • Japan, Fukuoka
    • Novartis Investigative Site Fukuoka-city, Fukuoka, Japan, 811-1395
  • Korea, Republic of, Gyeonggi Do
    • Novartis Investigative Site Seoul, Gyeonggi Do, Korea, Republic of, 03080
  • Korea, Republic of, Korea
    • Novartis Investigative Site Seoul, Korea, Korea, Republic of, 05505
  • Netherlands,
    • Novartis Investigative Site Amsterdam, , Netherlands, 1066
  • Singapore,
    • Novartis Investigative Site Singapore, , Singapore, 169610
  • Spain, Catalunya
    • Novartis Investigative Site Barcelona, Catalunya, Spain, 08035
  • Spain,
    • Novartis Investigative Site Madrid, , Spain, 28041
  • Taiwan, Taiwan ROC
    • Novartis Investigative Site Taipei, Taiwan ROC, Taiwan, 10041

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02108964
Other Study ID Numbers: 2013-004482-14
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Novartis:

NSCLC

Non-small Cell Lung Cancer EGFRmut

EGFR TKIs (EGF816)

acquired T790M mutation

de novo T790M mutation

EGFR TKI activating mutation (i.e. L858R or ex19del)

Treatment naive advanced NSCLC with EGFR activating mutations

Locally advanced NSCLC (Stage IIIB NSCLC not amenable to definitive multi-modality therapy including surgery)

Metastatic NSCLC refers to Stage IV NSCLC

1st line

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung

(R,E)-N-(7-chloro-1-(1-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-1H-benzo(d)imidazol-2-yl)-2-methylisonicotinamide

Nicotine

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on July 18, 2019