A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Participants With Advanced Solid Tumors

Advanced Solid Tumors Cancer Clinical Trial

Official title:

A Multicenter, Phase 1/1b, Open-Label, Dose-Escalation Study of ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02099058
• Other study ID #: M14-237
• Secondary ID: 2014-003154-14
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 15, 2014
• Est. completion date: November 16, 2024

Study information

• Verified date: June 2024
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1/1b open-label study evaluating the safety, pharmacokinetics (PK), and preliminary efficacy of ABBV-399 as monotherapy and in combination with osimertinib, erlotinib, and nivolumab in participants with advanced solid tumors likely to express c-Met. Enrollment is closed for the monotherapy arms, Arm A, and Arm D.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 237
• Est. completion date: November 16, 2024
• Est. primary completion date: November 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant must have advanced Non-Small Cell Lung Cancer (NSCLC) that is not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit.

• Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2. For Monotherapy Expansion Cohort, participant must have ECOG Performance Status of 0 or 1.

• Participant must have measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.

• Participant has archived diagnostic formalin-fixed paraffin embedded (FFPE) tumor tissue confirmed available for analyses.

• Participant has adequate bone marrow, renal, and hepatic function.

• Women of childbearing potential must have a negative serum pregnancy test at baseline.

• Participants in the combination therapy arms A and D must be eligible to receive erlotinib, or nivolumab per most locally approved labeling, or at the discretion of the Investigator.

• Participants in the combination therapy Arm E must satisfy following criteria.

• Participant must have metastatic/locally advanced nonsquamous NSCLC with documented Epidermal Growth Factor Receptor (EGFR) mutation(s) del19 or L858R, with or without T790M mutation, and none of the EGFR mutations known to be resistant to osimertinib.

• Participant must have received at least 1 but no more than 2 prior regimens, one of which must have contained osimertinib. Participant must have had disease progression while on osimertinib. Only 1 prior regimen may have contained chemotherapy. Consecutive EGFR TKIs will count as 1 regimen

• Participant must have available post-progression tumor tissue for central c-Met immunohistochemistry (IHC) testing.

• Participant has adequate bone marrow function.

• Participants in the Monotherapy Expansion Cohort must satisfy following criteria.

• Participant must have locally advanced or metastatic, non-squamous, EGFR wild type, c-Met+ NSCLC. Participants must not have adenosquamous histology.

• Participant must have received no more than 2 lines of prior systemic therapy (including no more than 1 line of systemic cytotoxic chemotherapy) in the locally advanced or metastatic setting.

• Participant must have progressed on systemic cytotoxic chemotherapy (or are ineligible for systemic cytotoxic chemotherapy) and an immune checkpoint inhibitor (as monotherapy or in combination with systemic cytotoxic chemotherapy, or ineligible for an immune checkpoint inhibitor), and prior anti-cancer therapies targeting driver gene alterations (if applicable).

• Participant should not have received prior c-Met-targeted antibody-based therapies.

Exclusion Criteria:

• Participant has received radiation therapy to the lung < 6 months prior to the first dose of ABBV-399.

• Participant has received anticancer therapy including chemotherapy, immunotherapy, biologic, or any investigational therapy within a period of 21 days or herbal therapy within 7 days prior to the first dose of ABBV-399.

• Participant has uncontrolled metastases to the central nervous system (CNS) based on head CT or MRI. Participants with brain metastases may be eligible 2-4 weeks after definitive therapy to all known sites of CNS disease provided they are asymptomatic and either off or on a non-increasing dose (in last 2 weeks) of systemic steroids and not on anticonvulsants for seizure activity directly related to progressive CNS metastases.

• Participant has history of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids.

• Participant has evidence of pulmonary fibrosis on screening imaging assessment or any history of pneumonitis or interstitial lung disease (ILD) within 3 months of the planned first dose of the study drug.

• Participant has unresolved clinically significant adverse events >= Grade 2 from prior anticancer therapy, except for alopecia or anemia.

• Participant has had major surgery within 21 days prior to the first dose of ABBV-399.

• Participant has a clinically significant condition(s) described in the protocol.

• History of major immunologic reaction to any Immunoglobulin G (IgG) containing agent.

• Participant has any medical condition which in the opinion of the Investigator or Medical Monitor places the participant at an unacceptably high risk for toxicities.

• Participant is a lactating or pregnant female.

• Participant with known active COVID-19 infection, subjects with signs/symptoms associated with COVID-19 infection or known exposure to a confirmed case of COVID-19 infection during 14 days prior to Screening must be screen failed and may only rescreen after they have recovered from COVID-19 and they are no longer considered contagious, per investigator assessment.

• Participants enrolled on the combination therapy phase must satisfy the above exclusion criteria and also the following:

• Participants may not receive ABBV-399 in combination with osimertinib, erlotinib or nivolumab if they have any medical condition which in the opinion of the Investigator places the participant at an unacceptably high risk for toxicities from the combination.

• Participants may not receive nivolumab if they have:

• Active autoimmune disease with exceptions of vitiligo, type I diabetes mellitus, hypothyroidism and psoriasis.

• Used systemic corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration, with exception of inhaled, locally injected or topical steroids.

• Known immunosuppressive disease, for example human immunodeficiency virus infection or history of bone marrow transplant or chronic lymphocytic leukemia.

• Participants may not be enrolled into the osimertinib Combination Therapy Arm E if they have the following:

• History of hypersensitivity to active or inactive excipients of osimertinib.

• History of osimertinib dose reduction.

• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib.

• Any of the following cardiac criteria: a) Mean resting corrected QT interval (QTc) > 470 ms; b) Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, e.g., complete left bundle branch block, second- or third-degree heart block, PR interval > 250 ms; c) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, or any concomitant medication known to prolong the QT interval.

Related Conditions & MeSH terms

• Advanced Solid Tumors Cancer
• Neoplasms

Intervention

Drug:
• Osimertinib
It is administered orally everyday.
• Nivolumab
It is an intravenous infusion administered every 14 days.
• Telisotuzumab vedotin
It is administered by infusion in 21-day dosing cycles.
• Telisotuzumab vedotin
It is administered by infusion in 28-day dosing cycles.
• Erlotinib
It is administered orally everyday.

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Antwerpen /ID# 170118	Edegem	Antwerpen
Finland	Duplicate_Tampere University Hospital /ID# 165065	Tampere	Pirkanmaa
France	AP-HM - Hopital de la Timone /ID# 151570	Marseille CEDEX 05	Bouches-du-Rhone
France	Institut Gustave Roussy /ID# 132747	Villejuif Cedex	Val-de-Marne
Italy	Duplicate_Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRCCS /ID# 164077	Meldola	Emilia-Romagna
Japan	National Cancer Center Hospital /ID# 217571	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East /ID# 217570	Kashiwa-shi	Chiba
Korea, Republic of	Asan Medical Center /ID# 217334	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Yonsei University Health System Severance Hospital /ID# 217333	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Duplicate_The Catholic University of Korea, ST. Vincent's Hospital /ID# 233378	Suwon	Gyeonggido
Netherlands	Radboud Universitair Medisch Centrum /ID# 246908	Nijmegen	Gelderland
Taiwan	China Medical University Hospital /ID# 217494	Taichung
Taiwan	National Cheng Kung University Hospital /ID# 167175	Tainan
Taiwan	Taipei Veterans General Hosp /ID# 217392	Taipei
Taiwan	National Taiwan University Hospital /ID# 167173	Taipei City	Taipei
United States	Univ of Colorado Cancer Center /ID# 123759	Aurora	Colorado
United States	Dana-Farber Cancer Institute /ID# 168782	Boston	Massachusetts
United States	Massachusetts General Hospital /ID# 129804	Boston	Massachusetts
United States	Montefiore Medical Park at Eastchester /ID# 218445	Bronx	New York
United States	The University of Chicago Medical Center /ID# 136995	Chicago	Illinois
United States	Mary Crowley Cancer Research /ID# 123760	Dallas	Texas
United States	Henry Ford Health System /ID# 149857	Detroit	Michigan
United States	City of Hope /ID# 153759	Duarte	California
United States	Duke Cancer Center /ID# 123763	Durham	North Carolina
United States	Virginia Cancer Specialists - Fairfax /ID# 165708	Fairfax	Virginia
United States	Summit Medical Group-Florham Park /ID# 217651	Florham Park	New Jersey
United States	Ingalls Memorial Hosp /ID# 165876	Harvey	Illinois
United States	University of Texas MD Anderson Cancer Center /ID# 154648	Houston	Texas
United States	Northwell Health - Monter Cancer Center /ID# 218170	Lake Success	New York
United States	Herbert Herman Cancer Center /ID# 149858	Lansing	Michigan
United States	University of California, Los Angeles /ID# 148295	Los Angeles	California
United States	Tennessee Oncology, PLLC /ID# 129802	Nashville	Tennessee
United States	UC Irvine /ID# 165107	Orange	California
United States	University of California, Davis Comprehensive Cancer Center /ID# 129805	Sacramento	California
United States	Washington University-School of Medicine /ID# 143798	Saint Louis	Missouri
United States	Scottsdale Healthcare /ID# 123761	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Belgium,  Finland,  France,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.	Up to 24 Months
Primary	Recommended Phase 2 Dose (RPTD) of ABBV-399 when Administered as Monotherapy and in Combination with Osimertinib, Erlotinib or Nivolumab	The RPTD of ABBV-399 when administered as monotherapy and in combination with osimertinib, erlotinib or nivolumab will be determined during the dose escalation phase of the study. RPTD will be determined using available safety and pharmacokinetics data.	Up to 24 Months
Primary	Area under the curve (AUC) from time zero to the last measurable concentration AUC (0-t)	AUC (0-t) = Area under the serum concentration versus time curve from time zero (pre-dose) to the time of the last measurable concentration.	Up to 24 months
Primary	Maximum observed plasma concentration (Cmax)	Maximum observed plasma concentration (Cmax).	Up to 24 months
Primary	Time to Cmax (Tmax)	Time to Cmax (Tmax).	Up to 24 months
Primary	Terminal elimination half life	Terminal elimination half life.	Up to 24 months