Study of Mogamulizumab + Docetaxel in Subjects With Non-small Cell Lung Cancer

• Sponsor: Kyowa Kirin, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02358473
• Collaborator: (none)
• Enrollment: 13
• Locations: 5
• Arm: 1
• Duration (Months): 23
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety of mogamulizumab in combination with docetaxel in adult subjects with previously treated locally advanced or metastatic non-small cell lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Biological: mogamulizumab; Drug: Docetaxel	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label, Multicenter Phase 1 Study of Mogamulizumab (KW-0761) in Combination With Docetaxel in Previously Treated Subjects With Non-small Cell Lung Cancer (NSCLC)
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mogamulizumab + docetaxel Mogamulizumab will be given as monotherapy in a 4-week run-in period. Subjects will then receive up to 6 cycles of mogamulizumab in combination with docetaxel at appropriate intervals. Subjects may then continue to receive mogamulizumab, at the same dose administered in Cycle 1, once every 3 weeks as monotherapy.	Biological: mogamulizumab; Mogamulizumab will be administered by IV infusion.; Other Names: KW-0761 POTELIGEO® ; Drug: Docetaxel; Docetaxel will be administered by IV infusion.; Other Names: Taxotere Docecad DTX

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Reporting Adverse Events [Screening through 90 days after the last dose of study medication]

2. Number of Subjects Reporting Serious Adverse Events [Screening through 90 days after the last dose of study medication]

3. Number of Subjects Experiencing Dose-limiting Toxicity [First dose of study medications through 4 weeks after the last dose of study medication]

Secondary Outcome Measures

1. Overall Response Rate [One year]

2. Progression Free Survival by RECIST 1.1 [One year]

3. Overall Survival [One year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed Stage IIIB or IV advanced or metastatic NSCLC with measurable neoplastic disease. Sputum cytology alone is not considered an acceptable method of diagnosis;

• Prior therapy must meet all of the following criteria:

1. Subject has experienced disease progression or unacceptable toxicity/intolerance after receiving at least 1 systemic platinum-containing regimen;

2. Subject with a tumor of non-squamous histology must be tested for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangement. Subject with EGFR activating mutation or ALK rearrangement must have experienced disease progression or unacceptable toxicity/intolerance after receiving at least one EGFR tyrosine kinase inhibitor or ALK inhibitor;

3. Subject has received PD-1/PD-L1 blockade or has been informed of the results of relevant positive Phase 3 trials with these agents.

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 at baseline;

• Minimum life expectancy of 3 months;

• Agrees to use a medically effective method of contraception. Male subjects and women of child-bearing potential (WOCBP) must agree to use effective contraception, e.g., oral contraceptives, double barrier method (condom plus spermicide or diaphragm plus spermicide), or practice true abstinence from sexual intercourse during the study and for 3 months after the last dose. Women of child-bearing potential include female subjects who have experienced menarche and have not undergone surgical sterilization or are not postmenopausal (defined as amenorrhea ≥ 12 consecutive months without an alternative medical cause);

• WOCBP must have a negative serum pregnancy test within 7 days prior to receiving investigational product and a negative urine pregnancy test on Day 1 of each Cycle;

• Recovered (i.e., Grade ≤ 1 or to a baseline level) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other therapies for cancer (with the exception of alopecia for which no resolution is required and peripheral neuropathy which must have resolved to Grade ≤ 1 for subjects receiving prior taxane-based chemotherapy);

• Adequate organ function defined as below:

1. Total bilirubin ≤ upper limit of normal (ULN);

2. Hemoglobin (Hgb) ≥ 9.0 g/dL;

3. Serum creatinine (sCr) ≤ 1.5 x ULN;

4. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3;

5. Platelets ≥ 100 × 109/L;

• Sufficient archived tumor samples (if taken within 6 months prior to treatment may be submitted) available for PD assessments, or willingness to undergo a pre-treatment core needle biopsy, preferably of the primary tumor, in order to obtain such tissue;

• Willing and able to undergo a post-dose core needle biopsy.

Exclusion Criteria:

• Prior treatment with docetaxel or mogamulizumab;

• Requires administration of a prohibited medication or treatment;

• Has a significant uncontrolled intercurrent illness including, but not limited to:

1. Ongoing or active infection requiring antibiotics;

2. Clinically significant cardiac disease (class III, or IV of the New York Heart Association classification; unstable angina pectoris, myocardial infarction within 6 months or is post angioplasty or stenting within 6 months; clinically significant cardiac arrhythmia, or uncontrolled hypertension (i.e., systolic blood pressure > 150 mm Hg, diastolic blood pressure > 90 mmHg) despite anti-hypertensive medication;

3. Uncontrolled diabetes, active liver disease, poorly controlled chronic obstructive pulmonary disease, serious or non-healing wound, ulcer, or fracture;

4. Known or tests positive for human immunodeficiency virus, hepatitis B, or hepatitis C

5. Active known auto-immune disease with the exception of autoimmune thyroiditis, vitiligo, and alopecia;

6. Pleural effusion requiring repetitive drainage, i.e., an indwelling catheter or 2 thoracenteses with 6 weeks of the first dose of mogamulizumab;

• Received monoclonal antibodies (for any reason), chemotherapy, surgery, investigational therapy, or radiotherapy within 14 days of the first dose of mogamulizumab;

• Received live, attenuated vaccine within 28 days prior to the first dose of mogamulizumab;

• Use of immunosuppressive medication within 14 days before the first dose of mogamulizumab. Note: Inhaled, intranasal, intra-articular, or topical corticosteroids are allowed. Non-immunosuppresive doses of systemic steroids for adrenal replacement or for contrast allergy are allowed;;

• Any history or signs of central nervous system metastases;

• Any history or signs of pulmonary lymphangitic spread;

• Experienced a Grade 3 or higher hypersensitivity reaction to monoclonal antibodies or other therapeutic proteins, and the reaction could not be controlled or prevented on subsequent infusion with standard therapies such as antihistamines, 5-hydroxytryptamine (5-HT3) receptor antagonists, or corticosteroids;

• The subject has a history of severe hypersensitivity reactions to drugs formulated with polysorbate 80;

• History of second primary cancer within the past 5 years, with the exception of:

1. Curatively resected non-melanomatous skin cancer;

2. Curatively treated cervical intraepithelial neoplasia or prostate carcinoma with current prostate specific antigen (PSA) < 0.01 ng/mL; or

3. Curatively treated ductal carcinoma in situ of the breast;

• The subject is pregnant or breastfeeding.

• The subject has aspartate aminotransferase and/or alanine aminotransferase > 1.5 × ULN, with concomitant alkaline phosphatase > 2.5 × ULN.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Horizon Oncology	Lafayette	Indiana	United States	47905
2	John Hopkins University School of Medicine	Baltimore	Maryland	United States	21231
3	Gabrail Cancer Center Research	Canton	Ohio	United States	44718
4	MD Anderson	Houston	Texas	United States	77025
5	Cancer Therapy and Research Center	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Kyowa Kirin, Inc.

Investigators

• Study Director: Michael Kurman, Kyowa Kirin, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kyowa Kirin, Inc.
• ClinicalTrials.gov Identifier: NCT02358473
• Other Study ID Numbers: 0761-011
• First Posted: Feb 9, 2015
• Last Update Posted: Nov 30, 2018
• Last Verified: Aug 1, 2017

• Keywords provided by Kyowa Kirin, Inc.: Nonsmall Cell Lung Cancer; NSCLC; Non-Small-Cell Lung Carcinoma; Carcinoma, Non-Small Cell Lung; KW-0761; Mogamulizumab
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Docetaxel; Mogamulizumab

Study Results

Participant Flow

Arm/Group Title	Mogamulizumab + Docetaxel
Arm/Group Description	Mogamulizumab (1.0 mg/kg, iv) was administered as monotherapy once weekly for 4 weeks. Subsequently, subjects received mogamulizumab (1.0 mg/kg) in combination with docetaxel (75 mg/m2), as separate infusions, on Day 1 every 3-weeks for up to 6 cycles.
Period Title: Overall Study
STARTED	13
COMPLETED	0
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Mogamulizumab + Docetaxel
Arm/Group Description	Mogamulizumab (1.0 mg/kg, iv) was administered as monotherapy once weekly for 4 weeks. Subsequently, subjects received mogamulizumab (1.0 mg/kg) in combination with docetaxel (75 mg/m2), as separate infusions, on Day 1 every 3-weeks for up to 6 cycles.
Overall Participants	13
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 53.8%
>=65 years	6 46.2%
Sex: Female, Male (Count of Participants)
Female	8 61.5%
Male	5 38.5%
Region of Enrollment (Count of Participants)
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Reporting Adverse Events
Time Frame	Screening through 90 days after the last dose of study medication

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mogamulizumab + Docetaxel
Arm/Group Description	Mogamulizumab (1.0 mg/kg, iv) was administered as monotherapy once weekly for 4 weeks. Subsequently, subjects received mogamulizumab (1.0 mg/kg) in combination with docetaxel (75 mg/m2), as separate infusions, on Day 1 every 3-weeks for up to 6 cycles.
Measure Participants	13
Count of Participants [Participants]	13 100%

2. Primary Outcome

Title	Number of Subjects Reporting Serious Adverse Events
Time Frame	Screening through 90 days after the last dose of study medication

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mogamulizumab + Docetaxel
Arm/Group Description	Mogamulizumab (1.0 mg/kg, iv) was administered as monotherapy once weekly for 4 weeks. Subsequently, subjects received mogamulizumab (1.0 mg/kg) in combination with docetaxel (75 mg/m2), as separate infusions, on Day 1 every 3-weeks for up to 6 cycles.
Measure Participants	13
Count of Participants [Participants]	6 46.2%

3. Primary Outcome

Title	Number of Subjects Experiencing Dose-limiting Toxicity
Time Frame	First dose of study medications through 4 weeks after the last dose of study medication

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mogamulizumab + Docetaxel
Arm/Group Description	Mogamulizumab (1.0 mg/kg, iv) was administered as monotherapy once weekly for 4 weeks. Subsequently, subjects received mogamulizumab (1.0 mg/kg) in combination with docetaxel (75 mg/m2), as separate infusions, on Day 1 every 3-weeks for up to 6 cycles.
Measure Participants	13
Count of Participants [Participants]	1 7.7%

4. Secondary Outcome

Title	Overall Response Rate
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mogamulizumab + Docetaxel
Arm/Group Description	Mogamulizumab (1.0 mg/kg, iv) was administered as monotherapy once weekly for 4 weeks. Subsequently, subjects received mogamulizumab (1.0 mg/kg) in combination with docetaxel (75 mg/m2), as separate infusions, on Day 1 every 3-weeks for up to 6 cycles.
Measure Participants	7
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	Progression Free Survival by RECIST 1.1
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mogamulizumab + Docetaxel
Arm/Group Description	Mogamulizumab (1.0 mg/kg, iv) was administered as monotherapy once weekly for 4 weeks. Subsequently, subjects received mogamulizumab (1.0 mg/kg) in combination with docetaxel (75 mg/m2), as separate infusions, on Day 1 every 3-weeks for up to 6 cycles.
Measure Participants	7
Median (95% Confidence Interval) [months]	1.87

6. Secondary Outcome

Title	Overall Survival
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mogamulizumab + Docetaxel
Arm/Group Description	Mogamulizumab (1.0 mg/kg, iv) was administered as monotherapy once weekly for 4 weeks. Subsequently, subjects received mogamulizumab (1.0 mg/kg) in combination with docetaxel (75 mg/m2), as separate infusions, on Day 1 every 3-weeks for up to 6 cycles.
Measure Participants	7
Median (95% Confidence Interval) [months]	8.88

Adverse Events

Arm/Group Title	Mogamulizumab + Docetaxel
Arm/Group Description	Mogamulizumab (1.0 mg/kg, iv) was administered as monotherapy once weekly for 4 weeks. Subsequently, subjects received mogamulizumab (1.0 mg/kg) in combination with docetaxel (75 mg/m2), as separate infusions, on Day 1 every 3-weeks for up to 6 cycles.
All Cause Mortality
	Mogamulizumab + Docetaxel
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Mogamulizumab + Docetaxel
	Affected / at Risk (%)	# Events
Total	6/13 (46.2%)
Blood and lymphatic system disorders
Febrile neutropenia	1/13 (7.7%)
Cardiac disorders
Acute myocardial infarction	1/13 (7.7%)
Atrial fibrillation	1/13 (7.7%)
Cardiac failure congestive	1/13 (7.7%)
Gastrointestinal disorders
Vomiting	1/13 (7.7%)
General disorders
Pyrexia	1/13 (7.7%)
Infections and infestations
Sepsis	2/13 (15.4%)
Pneumonia Bacterial	1/13 (7.7%)
Septic shock	1/13 (7.7%)
Metabolism and nutrition disorders
Dehydration	1/13 (7.7%)
Renal and urinary disorders
Renal failure actue	1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	2/13 (15.4%)
Vascular disorders
Hypotension	1/13 (7.7%)
Other (Not Including Serious) Adverse Events
	Mogamulizumab + Docetaxel
	Affected / at Risk (%)	# Events
Total	12/13 (92.3%)
Blood and lymphatic system disorders
Neutrophil count decreased	4/13 (30.8%)
Neutropenia	2/13 (15.4%)
Anaemia	1/13 (7.7%)
Thrombocytopenia	1/13 (7.7%)
Cardiac disorders
Cardiac failure congestive	2/13 (15.4%)
Atrial fibrilliation	2/13 (15.4%)
Eye disorders
Deafness	1/13 (7.7%)
Gastrointestinal disorders
Nausea	5/13 (38.5%)
Diarrhea	3/13 (23.1%)
Vomiting	2/13 (15.4%)
Haemorrhoids	1/13 (7.7%)
Dyspepsia	1/13 (7.7%)
Abdominal hernia	1/13 (7.7%)
Stomatitis	1/13 (7.7%)
Abdominal pain	1/13 (7.7%)
General disorders
Fatigue	6/13 (46.2%)
Pyrexia	4/13 (30.8%)
Pain	2/13 (15.4%)
Asthenia	1/13 (7.7%)
Chest pain	1/13 (7.7%)
Peripheral swelling	1/13 (7.7%)
Chills	1/13 (7.7%)
Local swelling	1/13 (7.7%)
Oedema peripheral	1/13 (7.7%)
Infections and infestations
Pneumonia	2/13 (15.4%)
Sepsis	2/13 (15.4%)
Thrush	1/13 (7.7%)
Oral candidiasis	1/13 (7.7%)
Urinary tract infection	1/13 (7.7%)
Injury, poisoning and procedural complications
Procedural site reaction	1/13 (7.7%)
Laceration	1/13 (7.7%)
Fall	1/13 (7.7%)
Post procedural oedema	1/13 (7.7%)
Infusion related reaction	1/13 (7.7%)
Investigations
Platelet count decreased	1/13 (7.7%)
Metabolism and nutrition disorders
Decreased appetite	4/13 (30.8%)
Dehydration	3/13 (23.1%)
Weight decreased	2/13 (15.4%)
Hyperuricaemia	1/13 (7.7%)
Hypomagnesaemia	1/13 (7.7%)
Hypokalemia	1/13 (7.7%)
Gout	1/13 (7.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/13 (15.4%)
Musculoskeletal pain	1/13 (7.7%)
Bone pain	1/13 (7.7%)
Musculoskeletal chest pain	1/13 (7.7%)
Back pain	1/13 (7.7%)
Myalgia	1/13 (7.7%)
Neck pain	1/13 (7.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system	1/13 (7.7%)
Nervous system disorders
Paraesthesia	2/13 (15.4%)
Dizziness	1/13 (7.7%)
Balance disorder	1/13 (7.7%)
Neuropathy peripheral	1/13 (7.7%)
Hypoaesthesia	1/13 (7.7%)
Headache	1/13 (7.7%)
Psychiatric disorders
Anxiety	1/13 (7.7%)
Mental status change	1/13 (7.7%)
Insomnia	1/13 (7.7%)
Disorientation	1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/13 (23.1%)
Paranasal sinus hypersecretion	1/13 (7.7%)
Cough	1/13 (7.7%)
Haemoptysis	1/13 (7.7%)
Dyspnea exertional	1/13 (7.7%)
Hypoxia	1/13 (7.7%)
Productive cough	1/13 (7.7%)
Skin and subcutaneous tissue disorders
Alopecia	2/13 (15.4%)
Rash	2/13 (15.4%)
Palmer-plantar erythrodysaesthesia syndrome	1/13 (7.7%)
Rash macular	1/13 (7.7%)
Rash papular	1/13 (7.7%)
Night sweats	1/13 (7.7%)
Rash maculo-papular	1/13 (7.7%)
Skin exfoliation	1/13 (7.7%)
Vascular disorders
Orthostatic hypotension	2/13 (15.4%)
Hypertension	1/13 (7.7%)
Hypotension	1/13 (7.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.