This Phase II study will recruit 40 metastatic non-small cell lung cancer patients who failed treatment with a platinum-containing doublet treatment and an anti-PD1 or PD-L1 immune checkpoint antibody, administered simultaneously or sequentially. All recruited patients will receive AB-16B5 at a dose of 12 mg/kg once weekly combined with docetaxel at a dose of 75 mg/m2 once every 3 weeks.
This is an open-label, single-arm, multi-center Phase II trial of AB-16B5 in combination with docetaxel in previously treated subjects with metastatic non-small cell lung cancer who have experienced disease progression following treatment with a platinum-containing doublet treatment and an anti-PD1 or PD-L1 immune checkpoint antibody, administered simultaneously or sequentially. Approximately 40 subjects will be enrolled in this trial and receive AB-16B5 at a dose of 12 mg/kg once weekly on Days 1, 8 and 15 combined with docetaxel at a dose of 75 mg/m2 once every 3 weeks on Day 1. One cycle of treatment will consist of 21 days (3 weeks). The safety profile of the AB-16B5 and docetaxel combination will be examined during a safety lead-in period with the first 8 subjects completing one cycle of treatment. No dose escalation will be performed but a decision to de-escalate the AB-16B5 dose could be made using the modified toxicity probability interval method. Subjects will be evaluated every 6 weeks with radiographic imaging to assess response to treatment using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for determination of the objective response rate (ORR) and progression free survival (PFS). Paired tumor biopsies (pre-treatment and on-treatment) will be collected in all subjects. Study treatment will continue until there is evidence of disease progression, treatment-related adverse events of unacceptable severity, subject request for discontinuation or Investigator determination that further treatment is not in the subject's best interest. Treatment through progression will be allowed if the Investigator considers the subject to be clinically stable. Subjects who must discontinue docetaxel due to toxicity will continue on AB-16B5.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
AB-16B5 is an inhibitor of the epithelial to mesenchymal transition. It is a fully humanized monoclonal antibody of IgG2 isotype against tumor-associated secreted clusterin (TA-sCLU).
Docetaxel is an anticancer chemotherapy drug approved in the treatment of non-small cell lung cancer
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Hôpital Maisonneuve-Rosemont
Montreal, Quebec, Canada
Centre Hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, Canada
Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ)
Québec, Quebec, Canada
Objective Response Rate (ORR)
Objective response rate (ORR) was defined as the percent of subjects documented to have a confirmed complete response (CR) or partial response (PR) as per RECIST 1.1 where Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions.
Time frame: Every 6 weeks until the date of objectively documented progression for up to 2 years.
Clinical Benefit Rate (CBR)
Clinical benefit rate (CBR) was defined as the percentage of subjects with complete response (CR), partial response (PR) or stable disease (SD) as per RECIST 1.1 where Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions; Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Every 6 weeks until the date of objectively documented progression for up to 2 years.
Duration of Response (DOR)
Duration of response (DOR) was defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of objective progression of disease (PD) as per RECIST 1.1 or to death due to any cause in the absence of documented PD. DOR was calculated only for the subjects achieving a confirmed CR or PR. As per RECIST 1.1, Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions, or the appearance of one or more new lesions.
Time frame: Every 6 weeks until the date of objectively documented progression for up to 2 years.
Duration of Clinical Benefit
Duration of clinical benefit (CB) was defined as the time from date of the first documentation of clinical benefit (either CR, PR or SD) to the first documentation of objective progression of disease (PD) as per RECIST 1.1 or to death due to any cause in the absence of documented PD. Duration of clinical benefit was calculated only for the subjects achieving a clinical benefit. As per RECIST 1.1, Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions; Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions, or the appearance of one or more new lesions.
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Centre Intégré de Santé et de Services Sociaux des Laurentides (Hôpital Régional de St-Jérôme)
Saint-Jérôme, Quebec, Canada
Time frame: Every 6 weeks until the date of objectively documented progression for up to 2 years.
Duration of Stable Disease
Duration of stable disease (SD) was defined as the time from the date of the first study treatment to the first documentation of objective progression of disease (PD) as per RECIST 1.1 or to death due to any cause in the absence of documented PD. Duration of stable disease was calculated only for the subjects achieving a stable disease as their best overall response. The best overall response was defined as the best response recorded from the start of the study treatment until the end of study. As per RECIST 1.1, Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions, or the appearance of one or more new lesions.
Time frame: Every 6 weeks until the date of objectively documented progression for up to 2 years.
Progression Free Survival (PFS)
Progression-free survival (PFS) was defined as the time from the date of first study treatment to the first documentation of objective progression of disease (PD) as per RECIST 1.1 or to death due to any cause in the absence of documented PD. For subjects who remained alive without progression at the end of the study, the event date was censored at the date of last disease assessment. As per RECIST 1.1, Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions, or the appearance of one or more new lesions.
Time frame: Every 6 weeks until the date of objectively documented progression for up to 2 years.
Overall Survival (OS)
Overall survival (OS) was defined as the time from date of first study treatment to death due to any cause. For surviving subjects at the end of the study, the OS endpoint was censored at the date of last contact (or last date known to be alive).
Time frame: From the start of study treatment up to the date of death or date of last contact for up to 3 years.