Docetaxel + Plinabulin Compared to Docetaxel + Placebo in... | NCT02504489

Description Module

Detailed Description

Lung cancer is the leading cause of cancer-related mortality worldwide. According to the World Health Organization's Global Cancer Observatory, there were an estimated 2.09 million new cases and 1.76 million deaths worldwide in 2018 (GLOBOCAN, 2018, Fact Sheet N⁰39). The lung cancer incidence and mortality in China is relatively high compared to most countries with an estimated 774,323 new cases and 690,567 deaths in 2018 (GLOBOCAN, 2018, Fact Sheet N⁰160 China). In the US, as per the estimates of the National Cancer Institute, there would be about 228,820 new cases and 135,720 deaths from lung cancer in 2020 accounting for approximately 22.4% of all cancer deaths (SEER program, 2020). About 84% of lung cancers are NSCLCs in the US (American Cancer Society, 2020).

The prognosis for patients with advanced or metastatic NSCLC, either at initial diagnosis or recurrence, remains grim. The standard of care has been chemotherapy with agents including platinum analogs, taxanes, vinca alkaloids, and pemetrexed with vascular endothelial growth factor inhibitors and for patients with appropriate disease genotypes, epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors.

First-line Therapy: For patients without specific molecular target, first-line therapy is usually a programmed cell death protein 1 (PD-1)-inhibitor or a platinum-containing, double agent regimen. Platinum can be either cisplatin or carboplatin, and the most commonly used drugs combined with platinum include paclitaxel, docetaxel, gemcitabine, and vinorelbine; other drugs such as irinotecan, etoposide, and vinblastine.

The arrival of immunotherapy with the PD-1 inhibitor pembrolizumab effectively changed the first-line standard. Pembrolizumab is very effective, with a long Duration of Response (DoR), however response rates remain suboptimal (approximately 45% in first line [Keytruda® Prescribing Information. 2020]). Most patients will eventually fail first line therapy and docetaxel remains a valid treatment option when NSCLC patients fail to respond to targeted or immune-based therapies or become refractory to such therapies.

For patients intolerant to platinum-containing regimens, platinum-free double-agent chemotherapy regimens are used as an alternative. For patients with an Eastern Cooperative Oncology Group score of 2 and elderly patients, single-agent or double agent regimens are recommended. Approval has been obtained in China for the single agent gefitinib to be used in first-line treatment of locally advanced or metastatic NSCLC patients with sensitive mutation of EGFR tyrosine kinase gene.

Second-line Therapy: Drugs used for second-line treatment include docetaxel, pemetrexed, EGFR-tyrosine kinase inhibitor (TKI) for EGFR mutant patients, and the checkpoint inhibitors (such as nivolumab and pembrolizumab).

Several second-line treatment drugs and regimens (docetaxel, pemetrexed, and ramucirumab combined with docetaxel) have been approved as single agents or combination for second-line therapy for locally advanced or metastatic NSCLC with EGFR wild type with limited efficacy, characterized by limited clinical improvement or overall survival (OS). EGFR wild type represents around 85% of western NSCLC population, and around 70% of Asian NSCLC population. Checkpoint inhibition with PD 1/programmed death-ligand 1 (PD-L1) inhibitors in combination with chemotherapy or other checkpoint inhibitors have moved into first line and are increasingly not an option for 2nd/3rd line. This has created a situation where docetaxel-based regimens have become standard-of-care in 2nd/3rd line NSCLC. Therefore, the evaluation of plinabulin combined with docetaxel versus docetaxel alone has become highly relevant.

Docetaxel, a taxane, binds to and stabilizes tubulin, thereby inhibiting microtubule disassembly resulting in cell cycle arrest at the G2/M phase and subsequent cell death. In patients with NSCLC, previously treated with a platinum-based chemotherapy, second-line therapy with docetaxel afforded a median OS in the range from 5.7 to 7.5 months (Fossella, 2000; Shepherd, 2000). The most common AEs included infections, neutropenia, anemia, febrile neutropenia (FN), hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions, and myalgia (Taxotere Prescribing Information, 2020). Since the approval of docetaxel in 1999 as the second-line treatment for advanced or metastatic NSCLC, other drugs, namely pemetrexed and erlotinib, have been approved for the same indication. However, despite the availability of newer treatments, patient survival has not improved over that achieved with docetaxel. The OS in these studies was found to remain in the range of 5.6 to 8.3 months (Hanna et al., 2004; Kim et al., 2008; Shepherd et al., 2005).

A retrospective analysis of the plinabulin Phase 2 study suggests that plinabulin prolongs survival in NSCLC patients with measurable lung tumors. The expectation is that patients with a measurable lung lesion may still harbor antigens that are immunogenic, thus capable of still stimulating the immune system. Docetaxel treatment is expected to release these immunogens and plinabulin is expected to enhance presentation of these immunogens via dendritic cell activation, to the T-cell repertoire.

This plinabulin study investigates the efficacy and safety of plinabulin and docetaxel combination in patients with EGFR wild type NSCLC and progressing tumors requiring second- or third- line therapy for advanced or metastatic disease after failing a platinum-containing regimen. The primary endpoint is OS, with docetaxel monotherapy as an active comparator.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Docetaxel (D)	Active Comparator	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction.	Drug: Docetaxel (D)
Docetaxel + Plinabulin (DP)	Experimental	The treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade >1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described.	Drug: Docetaxel + Plinabulin (DP) Drug: Docetaxel (D)

Name	Type	Description	Arm Group Labels	Other Names
Docetaxel + Plinabulin (DP)	Drug	Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2	Docetaxel + Plinabulin (DP)

Measure	Description	Time Frame
Overall Survival	Overall survival is defined as the time (days) from the date of randomization to the date of death due to any cause (i.e., Date of death - date of randomization +1).	The time (Days) from the date of randomization to the date of death, up to 48 months

Measure	Description	Time Frame
ORR	Overall response rate	up to 2 years after study Initiation
PFS	Progress-free survival	Up to 48 months after study initiation.

Eligibility Module

Eligibility Criteria

INCLUSION CRITERIA:

Males and females ≥ 18 years of age
ECOG performance status ≤ 2.
Histopathologically or cytologically confirmed non-squamous or squamous NSCLC.
Disease progression during or after treatment with one or two treatment regimen(s) Treatment regimens can be chemotherapy, targeted therapy, biological therapy, or immunotherapy for advanced (Stage IIIB) or metastatic disease (Stage IV). Modification of a regimen to manage toxicity with a different drug does not constitute a new regimen. Maintenance therapy following platinum-based chemotherapy is not considered as a separate regimen. Adjuvant or neoadjuvant chemotherapy and/or chemo-radiation for early stage disease do not count as prior systemic therapy. Prior radiation therapy is not exclusionary. Prior immunotherapy with a PD-1/PD-L1 inhibitor is not exclusionary. Prior treatment for advanced or metastatic disease must have included a platinum-based regimen. (Treatment of early stage disease [Stage IIIA or earlier] with a platinum-containing therapy does not count).
Patients with active brain metastasis or leptomeningeal involvement with brain metastases who are asymptomatic, and whose lesions by imaging are at least stable and without interim development of new lesions for at least 4 weeks may be enrolled. Patients who require continued therapy with steroid medication for management for their brain metastases are eligible; dosing must be stable for at least 4 weeks prior to randomization;
Patients must have at least one measurable lung lesion of ≥10 mm by CT or MRI per RECIST 1.1 criteria. Radiographic tumor assessment is to be performed within 28 days prior to randomization;
All patients with non-squamous NSCLC must have been tested for 19 deletion and exon 21 L858R substitution mutation. Only patients without EGFR sensitizing mutations are eligible, and they must have progressed on platinum-based chemotherapy. Patients with known ALK-rearrangements should be treated with an appropriate tyrosine kinase inhibitor (TKI) before entering the study. The TKI regimen would count as a line of treatment.
All adverse events of any prior systemic therapy, surgery, or radiotherapy, must have resolved to CTCAE (v4.03) Grade ≤2, except for neurological adverse events that must have resolved to Grade ≤1;
The following laboratory results from the central laboratory within 14 days prior to Cycle 1 Day 1 study drug administration.
- Hemoglobin ≥9 g/dL independent of transfusion or growth factor support;
- Absolute neutrophil count ≥1.5 x 109/L independent of growth factor support;
- Platelet count ≥100 x 109/L independent of transfusion or growth factor support;
- Serum total bilirubin ≤ ULN, unless the patient has a diagnosis of Gilbert's disease in which case serum bilirubin ≤3.0 times ULN;
- AST and ALT ≤2.5 x ULN (≤1.5 x ULN if alkaline phosphatase is >2.5 x ULN);
- Serum creatinine ≤1.5 x ULN;
Life expectancy more than 12 weeks;
Female patients of childbearing potential have a negative pregnancy test at baseline. Females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression.
1. Women of childbearing potential (i.e., menstruating women) must have a negative urine pregnancy test (positive urine tests are to be confirmed by serum test) documented within the 24-hour period prior to the first dose of study drug.
2. Sexually active women of childbearing potential enrolled in the study must agree to use two forms of accepted methods of contraception during the course of the study and for 3 months after their last dose of study drug. Effective birth control includes (a) intrauterine device (IUD) plus one barrier method; (b) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus one barrier method; (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm); or (d) a vasectomized partner.
3. For male patients who are sexually active and who are partners of premenopausal women: agreement to use two forms of contraception as in criterion 11b above during the treatment period and for at least 3 months after the last dose of study drug.
Signed informed consent.

EXCLUSION CRITERIA: Patients with any of the following:

Administration of chemotherapy, immunotherapy, biological, targeted, or radiation therapy or investigational agent (therapeutic or diagnostic) within 3 weeks prior to receipt of study medication. Major surgery, other than diagnostic surgery, within 4 weeks before first study drug administration.
Significant cardiac history:
- History of myocardial infarction or ischemic heart disease within 1 year (within a window of 18 days) before first study drug administration;
- Uncontrolled arrhythmia;
- History of congenital QT prolongation;
- ECG findings consistent with active ischemic heart disease;
- New York Heart Association Class III or IV cardiac disease;
- Uncontrolled hypertension: blood pressure consistently greater than 150 mm Hg systolic and 100 mm Hg diastolic in spite of antihypertensive medication.
Patients who have received prior treatment with docetaxel.
Prior transient ischemic attack or cerebrovascular accident within the past year (within an 18-day window). Any neurologic toxicities ≥ Grade 2 within 3 weeks of randomization.
History of hemorrhagic diarrhea, inflammatory bowel disease or active uncontrolled peptic ulcer disease. (Concomitant therapy with ranitidine or its equivalent and/or omeprazole or its equivalent is acceptable). History of ileus or other significant gastrointestinal disorder known to predispose to ileus or chronic bowel hypomotility.
Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
Known infection with human immunodeficiency virus (HIV) or active hepatitis A, B, or C.
Known prior hypersensitivity reaction to any product containing polysorbate 80, polyoxyethylene 15 hydroxystearate/Macrogol 15 hydroxystearate (Solutol HS 15/ Kolliphor HS 15).
Female subject who is pregnant or lactating.
Second malignancy unless in remission for >5 years. (Non-melanoma skin cancer or carcinoma in situ of the cervix treated with curative intent is not exclusionary).
Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient. Examples of such conditions include uncontrolled diabetes, infection requiring parenteral anti-infective treatment, liver failure, any altered mental status or any psychiatric condition that would interfere with the understanding of the informed consent form.
Unwilling or unable to comply with procedures required in this protocol.

Facility	Status	City	State	ZIP	Country	Contacts
Ironwood Cancer & Research Centers		Chandler	Arizona	85224	United States
Pacific Cancer Medical Center, Inc.

PubMed Identifier	Type	Citation	Retractions
39265599	Derived	Han B, Feinstein T, Shi Y, Chen G, Yao Y, Hu C, Shi J, Feng J, Wu H, Cheng Y, Guo QS, Jie Z, Ye F, Zhang Y, Liu Z, Mao W, Zhang L, Lu J, Zhao J, Bazhenova L, Ruiz J, Kloecker GH, Sujith KR, Oliff IA, Wong M, Liu B, Wu Y, Huang L, Sun Y; DUBLIN-3 study group. Plinabulin plus docetaxel versus docetaxel in patients with non-small-cell lung cancer after disease progression on platinum-based regimen (DUBLIN-3): a phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial. Lancet Respir Med. 2024 Oct;12(10):775-786. doi: 10.1016/S2213-2600(24)00178-4. Epub 2024 Sep 9.

Label	URL
BeyondSpring Pharmaceuticals, Inc. Web-site	View source

ID	Title	Description
FG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 19, 2021	Oct 10, 2025

Arm/Group Information

ID	Title	Description
BG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV
BG001	Docetaxel + Plinabulin (DP)	The treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade >1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described. Docetaxel + Plinabulin (DP): Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2 Docetaxel (D): Docetaxel 75 mg/m2 IV
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00059.8± 9.41 BG00160.6± 8.96 BG00260.2± 9.19

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00074 BG00179 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Tumor histology

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Non-squamous	BG000178 BG001154 BG002

ECOG score

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
0 (Fully active, able to carry on all pre-disease performance without restriction)	BG00044 BG00140 BG002

Regional distribution

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Asian	BG000245 BG001243 BG002

Cancer stage

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
IIIB (The Cancer has spread extensively to the lymph nodes in the chest)	BG00041 BG00150 BG002

Previous PD-1 or PD-L1 therapy received

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Yes	BG00057 BG00149 BG002

Line of previous therapy

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
First-line	BG000212 BG001204 BG002

Previous radiotherapy

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Yes	BG00084 BG00187 BG002

Previous surgery

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Yes	BG000138 BG001123 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Survival

Overall survival is defined as the time (days) from the date of randomization to the date of death due to any cause (i.e., Date of death - date of randomization +1).

All randomized participants

Posted

Median

95% Confidence Interval

months

The time (Days) from the date of randomization to the date of death, up to 48 months

ID	Title	Description
OG000	Docetaxel Plus Placebo (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV
OG001	Docetaxel + Plinabulin (DP)	The treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade >1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described. Docetaxel + Plinabulin (DP): Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2 Docetaxel (D): Docetaxel 75 mg/m2 IV

Units	Counts
Participants	OG000281 OG001278

Title

Denominators

Categories

Title	Measurements
	OG0009.4(8.38 to 10.68) OG00110.5(9.34 to 11.87)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.0399		Hazard Ratio (HR)	0.82			2-Sided	95	0.68	0.99					Other

Secondary

ORR

Overall response rate

All randomized participants

Posted

Count of Participants

Participants

up to 2 years after study Initiation

ID	Title	Description
OG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV
OG001	Docetaxel + Plinabulin (DP)	The treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade >1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described. Docetaxel + Plinabulin (DP): Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2 Docetaxel (D): Docetaxel 75 mg/m2 IV

Secondary

PFS

Progress-free survival

All randomized participants

Posted

Median

95% Confidence Interval

months

Up to 48 months after study initiation.

ID	Title	Description
OG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV
OG001	Docetaxel + Plinabulin (DP)	The treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade >1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described. Docetaxel + Plinabulin (DP): Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2 Docetaxel (D): Docetaxel 75 mg/m2 IV

Secondary

Severe Neutropenia

Percent of patients without severe neutropenia on Day 8 of Cycle 1

All participants who received at least 1 dose of study treatment

Posted

Count of Participants

Participants

Day 8 of Cycle 1 (±1 day)

ID	Title	Description
OG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV
OG001	Docetaxel + Plinabulin (DP)	The treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade >1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described. Docetaxel + Plinabulin (DP): Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2 Docetaxel (D): Docetaxel 75 mg/m2 IV

Secondary

Month 24 OS Rate

To compare 24-month overall survival rate

All randomized participants

Posted

Number

95% Confidence Interval

percentage of participants

up to 24months after study initiation

ID	Title	Description
OG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV
OG001	Docetaxel + Plinabulin (DP)	The treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade >1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described. Docetaxel + Plinabulin (DP): Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2 Docetaxel (D): Docetaxel 75 mg/m2 IV

Secondary

Month 36 OS Rate

To compare 36-month overall survival rate

All randomized participants

Posted

Number

95% Confidence Interval

percentage of participants

up to 36 months after study initiation

ID	Title	Description
OG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV
OG001	Docetaxel + Plinabulin (DP)	The treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade >1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described. Docetaxel + Plinabulin (DP): Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2 Docetaxel (D): Docetaxel 75 mg/m2 IV

Secondary

DoR

Duration of response

Posted

Median

95% Confidence Interval

months

Up to 2 years after study initiation.

ID	Title	Description
OG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV
OG001	Docetaxel + Plinabulin (DP)	The treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade >1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described. Docetaxel + Plinabulin (DP): Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2 Docetaxel (D): Docetaxel 75 mg/m2 IV

Secondary

Change From Baseline in EORTC QLQ-C30 Global Health Status / Quality of Life Score

The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status / Quality of Life scale was used.

The Global Health Status / Quality of Life scale is transformed to a 0-100 scale according to the EORTC scoring manual.

Minimum value: 0 Maximum value: 100 Higher scores indicate better quality of life The reported values represent the mean change from baseline to end of treatment (end of treatment score minus baseline score).

Posted

Mean

Standard Error

Score on a 0-100 scale

Baseline and End of Treatment (Last study assessment prior to treatment discontinuation), assessed up to 2 years after study initiation.

ID	Title	Description
OG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV
OG001	Docetaxel + Plinabulin (DP)

Secondary

Q-TWiST

To compare the mean difference in quality-adjusted time without symptoms of disease and toxicity

Posted

Mean

95% Confidence Interval

Months

up to 2 years after study initiation.

ID	Title	Description
OG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV
OG001	Docetaxel + Plinabulin (DP)	The treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade >1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described. Docetaxel + Plinabulin (DP): Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2 Docetaxel (D): Docetaxel 75 mg/m2 IV

Secondary

QoL (QLQ-LC13)

EORTC QLQ C30/QLQ LC13, this instrument consists of one multi-item dyspnea scale and several single item symptom scales (e.g. pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia and hemoptysis).

All LC13 symptom scales were scored according to the EORTC QLQ C30/QLQ LC13 scoring manuals. On this 0-100 scale, higher scores represent a higher level of symptoms (worse outcome).

The QLQ LC13 Symptom Combined Score used for this outcome is the average of all available LC13 symptom scale scores, if all 3 dyspnea items are non-missing, the dyspnea scale score and all other symptom scales are calculated and the Symptom Combined Score is the average of all available scales.

The reported LSMeans (SE) and LSMeans differences (95% CI) are based on this 0-100 Symptom Combined Score, where 0 indicates no lung cancer-related symptoms and 100 indicates the highest level of symptoms.

Posted

Least Squares Mean

Standard Error

score on a scale

Up to 2 years after study initiation.

ID	Title	Description
OG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV

Secondary

Proportion of Patients Who Received Docetaxel

To compare proportion of patients who received docetaxel >8 cycles, >10 cycles, and >12 cycles

All randomized participants

Posted

Count of Participants

Participants

Up to 29 cycles

ID	Title	Description
OG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV
OG001	Docetaxel + Plinabulin (DP)	The treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade >1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described. Docetaxel + Plinabulin (DP): Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2 Docetaxel (D): Docetaxel 75 mg/m2 IV

Secondary

Month 18 OS Rate

To compare 18-month overall survival rate

All randomized participants

Posted

Number

95% Confidence Interval

percentage of participants

up to 18 months after study initiation

ID	Title	Description
OG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV
OG001	Docetaxel + Plinabulin (DP)	The treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade >1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described. Docetaxel + Plinabulin (DP): Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2 Docetaxel (D): Docetaxel 75 mg/m2 IV

Secondary

Analysis of the Relative Dose Intensity of Docetaxel Over the First 4, 6, 8, 10, 12 Cycles

Relative Dose Intensity (RDI) was defined as the ratio of the actual delivered dose intensity to the planned dose intensity of docetaxel. Dose intensity was calculated as the total dose (mg/m²) divided by the actual cycle duration (days) and normalized to the planned 21-day treatment cycle. Thus, RDI = [(Actual dose / actual duration) / (Planned dose / 21 days)]. RDI values were summarized as mean (SD), median, and range per treatment group after 4, 6, 8, 10, and 12 cycles."

Note: Analysis population: ITT (Docetaxel [D] n=281; Docetaxel + Plinabulin [DP] n=278). Means (SD) were calculated using participants with available data at each duration; therefore, the number analyzed varies by row.

Evaluable population, defined as participants with available data for the analysis; the largest evaluable sample size was observed at Cycle 4.

Posted

Mean

Standard Deviation

Ratio (unitless)

First Cycle 1 Day 1 to the end of Cycle 12 (approximately up to 36 weeks)

ID	Title	Description
OG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV

Secondary

Month 12 OS Rate

To compare 12-month overall survival rate

All randomized participants

Posted

Number

95% Confidence Interval

percentage of participants

up to 12 months after study initiation

ID	Title	Description
OG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV
OG001	Docetaxel + Plinabulin (DP)	The treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade >1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described. Docetaxel + Plinabulin (DP): Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2 Docetaxel (D): Docetaxel 75 mg/m2 IV

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Docetaxel (D)	A treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction. Docetaxel (D): Docetaxel 75 mg/m2 IV	230	281	92	278	269	278
EG001	Docetaxel + Plinabulin (DP)	The treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade >1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described. Docetaxel + Plinabulin (DP): Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2 Docetaxel (D): Docetaxel 75 mg/m2 IV	214	278	115	274	270	274

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0 or later	Non-systematic Assessment	EG000112 affected278 at risk EG001120 affected274 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 21.0 or later	Systematic Assessment	EG00018 affected278 at risk EG00115 affected274 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.0 or later	Systematic Assessment	EG00063 affected278 at risk EG00193 affected274 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0 or later	Systematic Assessment	EG00047 affected278 at risk EG001101 affected274 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.0 or later	Systematic Assessment	EG00033 affected278 at risk EG00177 affected274 at risk
Constipation	Gastrointestinal disorders	MedDRA 21.0 or later	Systematic Assessment	EG00045 affected278 at risk EG00157 affected274 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 21.0 or later	Systematic Assessment	EG00014 affected278 at risk EG00135 affected274 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 21.0 or later	Systematic Assessment	EG0008 affected278 at risk EG00125 affected274 at risk
Malaise	General disorders	MedDRA 21.0 or later	Systematic Assessment	EG00046 affected278 at risk EG00157 affected274 at risk
Pyrexia	General disorders	MedDRA 21.0 or later	Systematic Assessment	EG00028 affected278 at risk EG00163 affected274 at risk
Stomatitis	General disorders	MedDRA 21.0 or later	Systematic Assessment	EG00032 affected278 at risk EG00131 affected274 at risk
Fatigue	General disorders	MedDRA 21.0 or later	Systematic Assessment	EG00030 affected278 at risk EG00132 affected274 at risk
Asthenia	General disorders	MedDRA 21.0 or later	Systematic Assessment	EG00020 affected278 at risk EG00129 affected274 at risk
Non-cardiac chest pain	General disorders	MedDRA 21.0 or later	Systematic Assessment	EG00015 affected278 at risk EG00122 affected274 at risk
Pain	General disorders	MedDRA 21.0 or later	Systematic Assessment	EG00012 affected278 at risk EG00115 affected274 at risk
Chills	General disorders	MedDRA 21.0 or later	Systematic Assessment	EG0004 affected278 at risk EG00115 affected274 at risk
Lung infection	Infections and infestations	MedDRA 21.0 or later	Systematic Assessment	EG00024 affected278 at risk EG00116 affected274 at risk
White blood cell count decreased	Investigations	MedDRA 21.0 or later	Systematic Assessment	EG000189 affected278 at risk EG001159 affected274 at risk
Neutrophil count decreased	Investigations	MedDRA 21.0 or later	Systematic Assessment	EG000196 affected278 at risk EG001140 affected274 at risk
Platelet count decreased	Investigations	MedDRA 21.0 or later	Systematic Assessment	EG00047 affected278 at risk EG00175 affected274 at risk
Blood pressure increased	Investigations	MedDRA 21.0 or later	Systematic Assessment	EG0009 affected278 at risk EG00191 affected274 at risk
Hepatic enzyme increased	Investigations	MedDRA 21.0 or later	Systematic Assessment	EG00039 affected278 at risk EG00139 affected274 at risk
Blood bilirubin increased	Investigations	MedDRA 21.0 or later	Systematic Assessment	EG00020 affected278 at risk EG00124 affected274 at risk
Lymphocyte count decreased	Investigations	MedDRA 21.0 or later	Systematic Assessment	EG00018 affected278 at risk EG00120 affected274 at risk
Weight decreased	Investigations	MedDRA 21.0 or later	Systematic Assessment	EG00014 affected278 at risk EG00119 affected274 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 21.0 or later	Systematic Assessment	EG00073 affected278 at risk EG00188 affected274 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 21.0 or later	Systematic Assessment	EG00027 affected278 at risk EG00135 affected274 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 21.0 or later	Systematic Assessment	EG00018 affected278 at risk EG00140 affected274 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 21.0 or later	Systematic Assessment	EG00018 affected278 at risk EG00130 affected274 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 21.0 or later	Systematic Assessment	EG0004 affected278 at risk EG00115 affected274 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 21.0 or later	Systematic Assessment	EG00030 affected278 at risk EG00123 affected274 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0 or later	Systematic Assessment	EG00019 affected278 at risk EG00121 affected274 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0 or later	Systematic Assessment	EG00014 affected278 at risk EG00114 affected274 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 21.0 or later	Systematic Assessment	EG00014 affected278 at risk EG00118 affected274 at risk
Peripheral neuropathy	Nervous system disorders	MedDRA 21.0 or later	Systematic Assessment	EG0008 affected278 at risk EG00119 affected274 at risk
Sleep disorder	Psychiatric disorders	MedDRA 21.0 or later	Systematic Assessment	EG00016 affected278 at risk EG00113 affected274 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0 or later	Systematic Assessment	EG00018 affected278 at risk EG00112 affected274 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 21.0 or later	Systematic Assessment	EG000118 affected278 at risk EG001117 affected274 at risk

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D000077143	Docetaxel
C514351	NPI 2358
C007792	Fumigant 93

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes