Dose-escalation Study of Lupartumab Amadotin (BAY1129980)

NCT02134197 | Terminated Phase 1 FDA Drug

• 1 other identifier: 16044
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 15

Brief Summary

The purpose of this study is to evaluate:

• The side effects of BAY1129980 when given every 21 days different dose levels.
• Determine the dose level of BAY1129980 that should be tested in future clinical research studies.
• Measure how much BAY1129980 is in the blood at specific times after administration.
• If treatment with BAY1129980 shows any effect on reducing the tumor growth.
• If there are specific biomarkers that might be able to explain why some patients respond to treatment and others do not.
• If treatment with BAY1129980 causes an immune response from the body against the drug (immunogenicity).

Conditions

Neoplasms

Keywords

Oncology; Solid tumors; Antibody drug conjugate; Maximum tolerated dose

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD)

  MTD is defined as the maximum dose at which the incidence of DLTs (dose limiting toxicities) during Cycle 1 is below 20%, or the maximum dose administered, whichever is achieved first during dose escalation.

  21 days

• Number of participants with adverse events as a measure of safety and tolerability

  Up to 2 years

Secondary Outcomes (4)

• C4.4a expression levels in tumour tissue as measured by immunohistochemistry (IHC)

  Baseline

• Tumor response evaluation following RECIST 1.1 criteria

  Up to 2 years

• Plasma concentration of BAY1129980 characterized by AUC (0-tlast)

  2 years

• Antidrug and antibody titer

  Baseline and up to 2 years

Study Arms (1)

Lupartumab Amadotin (BAY1129980)

EXPERIMENTAL

Dose escalation with consecutive expansion at MTD (maximum tolerated dose) with BAY1129980.

Drug: Lupartumab Amadotin (BAY1129980)

Interventions

Lupartumab Amadotin (BAY1129980) DRUG

Starting dose is 0.15mg/kg intravenous (I.V.) administration every 21 days.

Lupartumab Amadotin (BAY1129980)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must be ≥ 18 years at the first screening examination / visit
• All subjects must provide a tumor tissue sample from \[Formalin Fixed Paraffin Embedded (FFPE) slides\] archival tissue or fresh biopsy collected before Cycle 1, Day 1
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
• Life expectancy of at least 12 weeks
• Radiographically or clinically evaluable tumor. In the expansion phase, disease must be measurable according to RECIST 1.1.
• Adequate bone marrow, liver, and renal function
• Histologically or cytologically confirmed solid tumors known to express C4.4a (eg, carcinomas of the lung, head \& neck SCC, esophagus SCC (squamous cell carcinoma),colon, ovary, prostate, and breast) that are refractory to any standard therapy, or have no standard therapy available, or for which subjects actively refuse any treatment that would be regarded as standard and in whom, in the opinion of the investigator, experimental therapy with BAY1129980 may be beneficial.
• A signed informed consent must be obtained prior to any study-specific procedures.
• Measurable disease with at least one lesion that can be accurately measured in at least one dimension according to RECIST 1.1

You may not qualify if:

• Anticancer chemotherapy, experimental cancer therapy, or cancer immunotherapy within 4 weeks prior to first dose study drug. Anticancer therapy is defined as any agent or combination of agents with clinically proven anti tumor activity administered by any route with the purpose of affecting the malignancy, either directly or indirectly, including palliative and therapeutic endpoints.
• Skin toxicity including but not limited to erythema, rash, ulceration, and open wound that is still clinically present and considered as acute or chronic.
• Subjects with psoriasis or other severe skin disease (eg, autoimmune skin disease, active erythematous skin lesions, etc.)
• Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.
• Prior local radiotherapy is allowed if it is completed at least 4 weeks prior to the first dose of study drug and the subject has evaluable lesions not previously irradiated
• Significant liver dysfunction determined as Child-Pugh score B or C
• History of symptomatic metastatic brain or meningeal tumors unless the subject is \>3 months from the end of definitive therapy before the first dose of study drug and has clinically or radiologically no evidence of tumor growth.
• History of clinically significant cardiac disease.
• Anti-platelet drugs within 4 weeks prior to the first dose of study drug. Anti-platelet drugs are defined as any agent or combination of agents with clinically proven anti-thrombotic activity administered by any route with the purpose of affecting blood clotting ability of the subject.
• Participation in another clinical trial in which they received active therapy within 4 weeks prior to the first dose of study drug.
• Subjects with CNS symptoms should undergo a CT scan or MRI of the brain to exclude new or progressive brain metastases. Spinal cord metastasis is acceptable. However, subjects with spinal cord compression should be excluded.
• Subjects with severe renal impairment (GFR \<50 mL/min/1.73 m²) or on dialysis.
• History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of study drug.
• Current evidence or previous medical history of (ie, any absolute risk of latent infection) hepatitis B or C, any active hepatitis, or human immunodeficiency virus (HIV) infection. Active clinically serious infections \> CTCAE Grade 2.
• Major surgery or significant trauma within 2 weeks prior to the first dose of study drug.

Sponsors & Collaborators

• Bayer: lead

Study Sites (15)

Unknown Facility

La Jolla, California, 92093, United States

Location

Unknown Facility

Stanford, California, 94305, United States

Location

Unknown Facility

Aurora, Colorado, 80045, United States

Location

Unknown Facility

Washington D.C., District of Columbia, 20007-2197, United States

Location

Unknown Facility

Gainesville, Georgia, 32610, United States

Location

Unknown Facility

Westwood, Kansas, 66205, United States

Location

Unknown Facility

Hackensack, New Jersey, 07601, United States

Location

Unknown Facility

Buffalo, New York, 14263, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Durham, North Carolina, 27710, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19104, United States

Location

Unknown Facility

Nashville, Tennessee, 37203, United States

Location

Unknown Facility

Dallas, Texas, 75230, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Seattle, Washington, 98109-1023, United States

Location

Related Publications (1)

• Willuda J, Linden L, Lerchen HG, Kopitz C, Stelte-Ludwig B, Pena C, Lange C, Golfier S, Kneip C, Carrigan PE, Mclean K, Schuhmacher J, von Ahsen O, Muller J, Dittmer F, Beier R, El Sheikh S, Tebbe J, Leder G, Apeler H, Jautelat R, Ziegelbauer K, Kreft B. Preclinical Antitumor Efficacy of BAY 1129980-a Novel Auristatin-Based Anti-C4.4A (LYPD3) Antibody-Drug Conjugate for the Treatment of Non-Small Cell Lung Cancer. Mol Cancer Ther. 2017 May;16(5):893-904. doi: 10.1158/1535-7163.MCT-16-0474. Epub 2017 Mar 14.

  PMID: 28292941 DERIVED

MeSH Terms

Conditions

Neoplasms

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2014
• First Posted: May 9, 2014
• Study Start: May 22, 2014
• Primary Completion: August 30, 2018
• Study Completion: August 30, 2018
• Last Updated: December 11, 2019

Record last verified: 2019-12

Locations

US (15)