Protocol No.: OCR15173
Sponsor Protocol No.: 16044
An open-label Phase I dose-escalation study to evaluate the safety, tolerability, maximum tolerated dose, pharmacokinetics, and pharmacodynamics of the anti-C4.4a antibody drug conjugate BAY 1129980 in subjects with advanced solid tumors known to express C4.4a
This study is being conducted to determine if BAY1129980 is helpful in treating individuals with tumors expressing C4.4a.
The relatively restricted C4.4a expression pattern provides a target for the selective delivery of a cytotoxic drug to C4.4.a-expressing tumor cells by means of a suitable antibody-drug conjugate. The subject population eligible for the current study will be those subjects with advanced malignancies known to express C4.4a, which are refractory to standard therapy or those without standard therapy or actively refusing any treatment, which would be regarded as standard and in whom, in the opinion of the investigator, experimental therapy with BAY1129980 may be beneficial.Depending on the number of dose-escalating steps and the occurrence of DLTs, the planned numbers of subjects could vary.It is expected that up to 90 subjects may participate in the dose-expansion phase of the study and up to 6-9 subjects may participate in the dose re-escalation phase.The study assessments in the expansion phase of the study are identical to those in the dose-escalation phase.
Phase: Phase I
Age Group: Adult
Dose escalation with consecutive expansion at MTD (maximum tolerated dose) with BAY1129980. Starting dose is 0.15mg/kg intravenous (I.V.) administration every 21 days.
1. Ages 18 years old or older
2. 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
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
4. Life expectancy of at least 12 weeks
5. Radiographically or clinically evaluable tumor. In the expansion phase, disease must be measurable according to RECIST 1.1.
6. Adequate bone marrow, liver, and renal function
7. 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.
8. A signed informed consent must be obtained prior to any study-specific procedures.
9. Measurable disease with at least one lesion that can be accurately measured in at least one dimension according to RECIST 1.1
1. 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.
2. Skin toxicity including but not limited to erythema, rash, ulceration, and open wound that is still clinically present and considered as acute or chronic.
3. Subjects with psoriasis or other severe skin disease (eg, autoimmune skin disease, active erythematous skin lesions, etc.)
4. Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.
5. 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
6. Significant liver dysfunction determined as Child-Pugh score B or C
7. 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.
8. History of clinically significant cardiac disease.
9. 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.
10. Participation in another clinical trial in which they received active therapy within 4 weeks prior to the first dose of study drug.
11. 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.
12. Subjects with severe renal impairment (GFR 13. 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.
14. 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.
15. Major surgery or significant trauma within 2 weeks prior to the first dose of study drug.
** Contact study team for full eligibility details
Applicable Disease Sites
Head & Neck Cancer
UF Gainesville : Elena Nelson
Phone: +1 352-265-0680 ext. 50144
View study listing on ClinicialTrials.gov