A Study of DS-2248 in Participants With Advanced Solid Tumors

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01288430
• Collaborator: Daiichi Sankyo UK Ltd. (Other)
• Enrollment: 60
• Locations: 9
• Arm: 1
• Actual Duration (Months): 34.6
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase 1 clinical trial is intended to understand the safety and tolerability of a new anticancer drug in subjects with advanced solid tumors. The patients who qualify for the study will receive a once daily dose of the drug taken by mouth and will undergo several tests to measure the drug in the blood and to understand the safety, tolerability and any effect of the drug on the tumor. The antitumor effect of the drug is not known in human.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors; Non-small Cell Lung Carcinoma	Drug: DS-2248	Phase 1

Detailed Description

The study will be conducted in two parts. Part 1 is a dose escalation study in which subjects in each cohort will be given increasing doses of the study drug until a maximum tolerated dose (MTD) or maximum administered dose (MAD) is determined as the recommended phase 2 dose (RP2D). The drug will be administered as oral capsules once daily in 21 day cycles, with no interruption between cycles if no unacceptable treatment-related toxicity or tumor progression are observed.

After determining the RP2D, Part 2 of the study, which is a dose expansion study will begin in which subjects with advanced non-small cell lung cancer who developed acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI), erlotinib, gefitinib, afatinib (and others) or whose tumors carry an ALK translocation and are resistant to ALK inhibitor therapy, will be treated with DS-2248 at RP2D. The drug will be administered as oral capsules once daily in 21 day cycles, with no interruption between cycles if no unacceptable treatment-related toxicity or tumor progression are observed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-Label, Multiple-Ascending-Dose Study of DS-2248, an Orally Bioavailable Heat Shock Protein 90 Inhibitor, in Subjects With Advanced Solid Tumors
• Actual Study Start Date: Mar 29, 2011
• Actual Primary Completion Date: Feb 13, 2014
• Actual Study Completion Date: Feb 13, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: DS-2248 Study Part 1: DS-2248 oral capsule(s) of increasing strength in a dose escalation study in subjects with advanced solid tumors, administered once daily in 21-day cycles, with no interruption between cycles if no unacceptable treatment-related toxicity or tumor progression is observed. Study Part 2: DS-2248 oral capsule(s) dose of 4.5 mg/m^2, in subjects with non-small cell lung cancer who have developed acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors or whose tumors carry an ALK translocation and are resistant to ALK inhibitor therapy, administered once daily in 21 day-cycles, with no interruption between cycles if no unacceptable treatment-related toxicity or tumor progression are observed.

Drug: DS-2248; Oral capsules, of various strengths (1, 5 , 20 ,or 50 milligrams), once daily during 21-day cycles, until unacceptable treatment-related toxicity or tumor progression are observed.

Outcome Measures

Primary Outcome Measures

1. Summary of Objective Response Rate Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors [Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months]

   Objective response rate was defined as the sum of complete response (CR) and partial response (PR) rates. CR was defined as a disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Secondary Outcome Measures

1. Summary of Best Overall Response Rate Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors [Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months]

   Complete response (CR) was defined as a disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to <10 mm. Partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Objective response rate (ORR) was defined as the sum of CR and PR rates.

2. Summary of Disease Control Rate Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors [Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months]

   Disease control rate (DCR) was defined as the sum of complete response (CR) and partial response (PR) rates, and stable disease (SD) rate for a minimum of 12 weeks. Complete response (CR) was defined as a disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to <10 mm. Partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions), taking as reference the smallest sum diameters while on study.

3. Duration of Stable Disease Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors [Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months]

   Duration of response measured from the time at which criteria were first met for complete (CR) or partial response (PR) until the first date that progressive disease (PD) was objectively documented. Participants who had not progressed at the data cut-off date were censored at their last evaluable tumor assessment date. Duration of stable disease (SD) measured from the date of enrollment until the first date that criteria for disease progression were met. The minimum time interval for the duration of SD was 6 weeks. Participants who had not progressed at the data cut-off date were censored at their last evaluable tumor assessment date.

4. Summary of Progression-free Survival Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors [Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months]

   Progression-free survival (PFS) defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of radiographic disease progression (as per RECIST V1.1) or death due to any cause. Participants who were alive with no objective documentation of (radiographic) disease progression by the data cut-off date were censored at the date of their last evaluable tumor assessment. Participants who were lost to follow-up or withdrew early from the study with no documented disease progression were censored at the last evaluable tumor assessment.

5. Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve From Zero to Infinity Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors [Cycle 1, Day 1 predose, 0.5, 1, 2, 3, 4, 6, and 8 h postdose; Cycle 1, Day 2 and Day 15; Cycle 1, Day 8 predose, 1 and 6 h postdose; Cycle 2 and 3, Day 1, 8, and 15]

6. Summary of Pharmacokinetic Parameter Maximum Concentration Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors [Cycle 1, Day 1 predose, 0.5, 1, 2, 3, 4, 6, and 8 h postdose; Cycle 1, Day 2 and Day 15; Cycle 1, Day 8 predose, 1 and 6 h postdose; Cycle 2 and 3, Day 1, 8, and 15]

7. Summary of Pharmacokinetic Parameter Time at Maximum Concentration Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors [Cycle 1, Day 1 predose, 0.5, 1, 2, 3, 4, 6, and 8 h postdose; Cycle 1, Day 2 and Day 15; Cycle 1, Day 8 predose, 1 and 6 h postdose; Cycle 2 and 3, Day 1, 8, and 15]

8. Summary of Pharmacokinetic Parameter Terminal Half-life Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors [Cycle 1, Day 1 predose, 0.5, 1, 2, 3, 4, 6, and 8 h postdose; Cycle 1, Day 2 and Day 15; Cycle 1, Day 8 predose, 1 and 6 h postdose; Cycle 2 and 3, Day 1, 8, and 15]

9. Summary of Pharmacokinetic Parameter Total Body Clearance Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors [Cycle 1, Day 1 predose, 0.5, 1, 2, 3, 4, 6, and 8 h postdose; Cycle 1, Day 2 and Day 15; Cycle 1, Day 8 predose, 1 and 6 h postdose; Cycle 2 and 3, Day 1, 8, and 15]

10. Summary of Drug Related Treatment Emergent Adverse Events Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors [Baseline up to 30 days post last dose, up to 2 years 11 months]

    A treatment-emergent adverse event (TEAE) is defined as an adverse event that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pre-treatment state, when the AE is continuous. A DS-2248-related TEAE is an TEAE that is related to DS-2248 in the relationship.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. A pathologically documented advanced solid malignant tumor refractory to standard treatment or for which no standard treatment is available.

2. Eastern Cooperative Oncology Group (ECOG) performance status ≤1.

3. Have adequate bone marrow function, defined as:

• Platelet count ≥100x10^9/L or more.

• Hemoglobin (Hb) level ≥9.0 g/dL.

• Absolute neutrophil count ≥1.5 x 10^9/L.

1. Have adequate renal function, defined as:

• Creatinine clearance ≥60 mL/min, as calculated using the modified Cockcroft-Gault equation AND creatinine ≤1.5 times upper limit of normal(ULN).

1. Have adequate hepatic function, defined as:

• Aspartate aminotransferase (AST) levels ≤3 times ULN (if liver metastases are present, ≤5x ULN)

• Alanine aminotransferase (ALT) levels ≤3x ULN (if liver metastases are present, ≤5x ULN

• Bilirubin ≤1.5x ULN

1. Have adequate blood clotting function, defined as:

• Prothrombin time and activated partial thromboplastin time ≤1.5x ULN

1. Participants should be able to provide written informed consent, comply with protocol visits and procedures, be able to take oral medication, and not have any active infection or chronic co-morbidity that would interfere with therapy.

2. Participants (male and female) of childbearing/reproductive potential must agree to use double-barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug. If female and of childbearing potential, must have a negative result of a pregnancy test (serum or urine)within 72 hours prior to initiating study treatment. Surgically sterile individuals and postmenopausal females are considered not having child-bearing potential.

3. Participants must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an Institutional Review Board approved informed consent form (including Health Insurance Portability and Accountability Act authorization, if applicable) before performance of any study-specific procedures or tests.

4. Participants must be willing to provide pre-existing diagnostic or resected tumor samples, such as formalin-fixed paraffin-embedded sections, if available. Providing fresh pre-treatment tumor biopsy is optional for participants in dose escalation cohorts and in dose expansion Stage 1. Post-treatment biopsies are optional for all the participants in the study (dose escalation and dose expansion cohorts).

Additional Inclusion Criteria for Part 2 (Dose Expansion)

1. Pathologically documented stage IIIB/IV non-small cell lung cancer.

2. Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) criteria, Version 1.1.

3. Participants must meet 1 of the following 3 criteria in order to be included in Part 2:

4. Acquired resistance to reversible Epidermal Growth Factor Receptor-Tyrosine

Kinase Inhibitor (EGFR-TKI), which should meet the following criteria:

• Previous treatment with single-agent therapy (erlotinib, gefitinib, afatinib or others).

• Either of the following: A tumor that harbors an EGFR mutation known to be associated with drug sensitivity (i.e., G719X, exon 19 deletion, L858R, L861Q) -OR- Prior objective clinical benefit from EGFR-TKI, as evidenced by complete response (CR), partial response (PR), or stable disease (SD) ≥6 months as defined by RECIST or World Health Organization criteria.

• Systemic progression of disease as defined by RECIST or World Health Organization criteria while treatment with gefitinib, erlotinib, afatinib or others.

• No intervening therapy other than EGFR-TKIs (erlotinib, gefitinib, afatinib or others) after progression on an EGFR-TKI.

• Pre-treatment biopsy (performed via bronchoscopy or imaging guidance) for molecular testing of the tumor is desired but not mandatory for enrollment in Stage 1. However, pre-treatment biopsy within 21 days prior to the first day of treatment is required for enrollment in Stage 2.

1. Presence of ALK fusion gene in the tumor demonstrated by fluorescence in situ hybridization (FISH) and the participant has acquired resistance to ALK inhibitor therapy.

Exclusion Criteria:

1. History of second malignancies or primary central nervous system malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years.

2. Gastrointestinal diseases that could affect the absorption of DS-2248.

3. Subjects with peptic ulcer disease requiring on-going treatment with pH-modifiers

4. Subjects with history of inflammatory bowel disease.

5. Subjects with retinal or uveal diseases including macular degeneration with central vision loss, retinal detachment, diabetic retinopathy, and uveitis.

6. Recipient of a stem cell or bone marrow transplant.

7. Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor.

8. Clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 4 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (2 weeks for stereotactic radiotherapy).

9. Has unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0, Grade ≤1 or baseline. Subjects with chronic Grade 2 toxicities may be eligible per the discretion of the Investigator or Sponsor (e.g., Grade 2 chemotherapy-induced neuropathy).

10. Systemic treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy (except megestrol acetate as supportive care) within 3 weeks before study drug treatment; or treatment with nitrosoureas or mitomycin C within 6 weeks before study drug treatment; or treatment with small-molecule Tyrosine Kinase Inhibitors within 7 days for erlotinib and afatinib and 10 days for gefitinib before study drug treatment. Previous and concurrent use of hormone replacement therapy, the use of gonadotropin-releasing hormone modulators for prostate cancer, and the use of somatostatin analogs for neuroendocrine tumors are permitted.

11. Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug treatment.

12. Participation in a clinical drug study within 3 weeks for small-molecule TKIs before study drug treatment, or current participation in other investigational procedures.

13. Concomitant treatment with potent inducers or potent inhibitors of cytochrome P450 3A4 (CYP3A4).

14. Concomitant treatment with a medication known to cause renal tubular damage or reduce renal perfusion at the dose administered, including aminoglycosides, amphotericin B, pentamidine, nonsteroidal anti-inflammatory drugs, and zoledronate.

15. Corrected QT interval (QTc by Bazett's formula) prolongation at rest, where the mean QTc interval is >450 msec based on triplicate ECG.

16. Pregnant or breastfeeding.

17. Substance abuse or medical, psychological, or social conditions that may, in the opinion of the Investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results.

18. Less than 1 week since using systemically acting drugs that increase gastric pH, such as H2-blockers and proton pump inhibitors. Antacids should be avoided within 48 hours of the first dose of DS-2248.

19. Use of St. John's Wort (hypericin) is not permitted for 30 days before and during the study. Foods or beverages containing grapefruit should be avoided within 48 hours before and during the study.

Additional Exclusion Criteria for Part 2 (Dose Expansion)

1. Prior treatment with Hsp90 inhibitors

2. Intervening therapy after progression on an EGFR-TKI (erlotinib, gefitinib, afatinib or others), unless re-treated with EGFR-TKI.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Duarte	California	United States
2		Loma Linda	California	United States
3		Orange	California	United States
4		Orlando	Florida	United States
5		Indianapolis	Indiana	United States
6		Detroit	Michigan	United States
7		Portland	Oregon	United States
8		San Antonio	Texas	United States
9		Seattle	Washington	United States

Sponsors and Collaborators

• Daiichi Sankyo, Inc.
• Daiichi Sankyo UK Ltd.

Investigators

• Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT01288430
• Other Study ID Numbers: DS2248-A-U101; 2011-002666-21
• First Posted: Feb 2, 2011
• Last Update Posted: Oct 5, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Daiichi Sankyo, Inc.: Heat shock protein 90; Advanced solid tumors; Non-small cell lung carcinoma; Epidermal growth factor receptor; Tyrosine kinase inhibitor acquired resistance; Non-small cell lung carcinoma with acquired resistance to erlotinib, gefitinib, afatinib or others.
• Additional relevant MeSH terms: Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Study Results

Participant Flow

Recruitment Details	A total of 60 participants who met all inclusion and no exclusion criteria were enrolled in the study.
Pre-assignment Detail	Part 1: Dose escalation began with an accelerated titration design, with a starting dose of DS-2248 0.6 mg/m^2 once daily. Part 2: Dose expansion was assessed in participants with Stage IIIB/IV non-small cell lung cancer with resistance to epidermal growth factor receptor tyrosine kinase inhibitor or ALK inhibitor therapy.

Arm/Group Title	Part 1, Cohort 1: DS-2248 0.6 mg/m^2	Part 1, Cohort 2: DS-2248 1.2 mg/m^2	Part 1, Cohort 3: DS-2248 1.8 mg/m^2	Part 1, Cohort 4: DS-2248 2.7 mg/m^2	Part 1, Cohort 5: DS-2248 3.5 mg/m^2	Part 1, Cohort 6: DS-2248 4.5 mg/m^2	Part 1, Cohort 7: DS-2248 5.85 mg/m^2	Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-naive: DS-2248 4.5 mg/m^2
Arm/Group Description	Participants who received oral DS-2248 0.6 mg/m^2 once daily.	Participants who received oral DS-2248 1.2 mg/m^2 once daily.	Participants who received oral DS-2248 1.8 mg/m^2 once daily.	Participants who received oral DS-2248 2.7 mg/m^2 once daily.	Participants who received oral DS-2248 3.5 mg/m^2 once daily.	Participants who received oral DS-2248 4.5 mg/m^2 once daily.	Participants who received oral DS-2248 5.85 mg/m^2 once daily.	Participants who were epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK-inhibitor resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK treatment naive and received oral 4.5 mg/m^2 once daily.
Period Title: Part 1
STARTED	2	3	5	7	3	6	7	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	2	3	5	7	3	6	7	0	0	0
Period Title: Part 1
STARTED	0	0	0	0	0	0	0	12	12	3
COMPLETED	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	12	12	3

Baseline Characteristics

Arm/Group Title	Part 1, Cohort 1: DS-2248 0.6 mg/m^2	Part 1, Cohort 2: DS-2248 1.2 mg/m^2	Part 1, Cohort 3: DS-2248 1.8 mg/m^2	Part 1, Cohort 4: DS-2248 2.7 mg/m^2	Part 1, Cohort 5: DS-2248 3.5 mg/m^2	Part 1, Cohort 6: DS-2248 4.5 mg/m^2	Part 1, Cohort 7: DS-2248 5.85 mg/m^2	Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-naive: DS-2248 4.5 mg/m^2	Total
Arm/Group Description	Participants who received oral DS-2248 0.6 mg/m^2 once daily.	Participants who received oral DS-2248 1.2 mg/m^2 once daily.	Participants who received oral DS-2248 1.8 mg/m^2 once daily.	Participants who received oral DS-2248 2.7 mg/m^2 once daily.	Participants who received oral DS-2248 3.5 mg/m^2 once daily.	Participants who received oral DS-2248 4.5 mg/m^2 once daily.	Participants who received oral DS-2248 5.85 mg/m^2 once daily.	Participants who were epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK-inhibitor resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK treatment naive and received oral 4.5 mg/m^2 once daily.	Total of all reporting groups
Overall Participants	2	3	5	7	3	6	7	12	12	3	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	2 66.7%	3 60%	5 71.4%	2 66.7%	6 100%	4 57.1%	7 58.3%	8 66.7%	3 100%	40 66.7%
>=65 years	2 100%	1 33.3%	2 40%	2 28.6%	1 33.3%	0 0%	3 42.9%	5 41.7%	4 33.3%	0 0%	20 33.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	75.0 (0.0)	58.7 (16.6)	61.0 (10.8)	60.1 (11.9)	53.0 (17.4)	49.8 (11.6)	61.4 (12.9)	58.8 (11.2)	59.8 (11.8)	51.7 (2.5)	58.8 (12.9)
Sex: Female, Male (Count of Participants)
Female	1 50%	2 66.7%	4 80%	4 57.1%	1 33.3%	2 33.3%	2 28.6%	6 50%	5 41.7%	2 66.7%	29 48.3%
Male	1 50%	1 33.3%	1 20%	3 42.9%	2 66.7%	4 66.7%	5 71.4%	6 50%	7 58.3%	1 33.3%	31 51.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	3 25%	3 25%	0 0%	7 11.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 33.3%	0 0%	0 0%	0 0%	0 0%	1 14.3%	0 0%	1 8.3%	0 0%	3 5%
White	2 100%	2 66.7%	5 100%	7 100%	3 100%	5 83.3%	6 85.7%	9 75%	8 66.7%	3 100%	50 83.3%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%	3 100%	5 100%	7 100%	3 100%	6 100%	7 100%	12 100%	12 100%	3 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Summary of Objective Response Rate Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors
Description	Objective response rate was defined as the sum of complete response (CR) and partial response (PR) rates. CR was defined as a disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame	Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months

Outcome Measure Data

Analysis Population Description

Objective response rate was assessed in the Full Analysis Set.

Arm/Group Title	Part 1, Cohort 1: DS-2248 0.6 mg/m^2	Part 1, Cohort 2: DS-2248 1.2 mg/m^2	Part 1, Cohort 3: DS-2248 1.8 mg/m^2	Part 1, Cohort 4: DS-2248 2.7 mg/m^2	Part 1, Cohort 5: DS-2248 3.5 mg/m^2	Part 1, Cohort 6: DS-2248 4.5 mg/m^2	Part 1, Cohort 7: DS-2248 5.85 mg/m^2	Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-naive: DS-2248 4.5 mg/m^2
Arm/Group Description	Participants who received oral DS-2248 0.6 mg/m^2 once daily.	Participants who received oral DS-2248 1.2 mg/m^2 once daily.	Participants who received oral DS-2248 1.8 mg/m^2 once daily.	Participants who received oral DS-2248 2.7 mg/m^2 once daily.	Participants who received oral DS-2248 3.5 mg/m^2 once daily.	Participants who received oral DS-2248 4.5 mg/m^2 once daily.	Participants who received oral DS-2248 5.85 mg/m^2 once daily.	Participants who were epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK-inhibitor resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK treatment naive and received oral 4.5 mg/m^2 once daily.
Measure Participants	2	3	3	5	2	6	4	10	9	2
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Summary of Best Overall Response Rate Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors
Description	Complete response (CR) was defined as a disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to <10 mm. Partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Objective response rate (ORR) was defined as the sum of CR and PR rates.
Time Frame	Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months

Outcome Measure Data

Analysis Population Description

Best overall response was assessed in the Full Analysis Set.

Arm/Group Title	Part 1, Cohort 1: DS-2248 0.6 mg/m^2	Part 1, Cohort 2: DS-2248 1.2 mg/m^2	Part 1, Cohort 3: DS-2248 1.8 mg/m^2	Part 1, Cohort 4: DS-2248 2.7 mg/m^2	Part 1, Cohort 5: DS-2248 3.5 mg/m^2	Part 1, Cohort 6: DS-2248 4.5 mg/m^2	Part 1, Cohort 7: DS-2248 5.85 mg/m^2	Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-naive: DS-2248 4.5 mg/m^2
Arm/Group Description	Participants who received oral DS-2248 0.6 mg/m^2 once daily.	Participants who received oral DS-2248 1.2 mg/m^2 once daily.	Participants who received oral DS-2248 1.8 mg/m^2 once daily.	Participants who received oral DS-2248 2.7 mg/m^2 once daily.	Participants who received oral DS-2248 3.5 mg/m^2 once daily.	Participants who received oral DS-2248 4.5 mg/m^2 once daily.	Participants who received oral DS-2248 5.85 mg/m^2 once daily.	Participants who were epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK-inhibitor resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK treatment naive and received oral 4.5 mg/m^2 once daily.
Measure Participants	2	3	3	5	2	6	4	10	9	2
Confirmed CR	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Confirmed PR	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Stable disease	1 50%	1 33.3%	3 60%	0 0%	0 0%	2 33.3%	2 28.6%	4 33.3%	2 16.7%	1 33.3%
Progressive disease	1 50%	1 33.3%	0 0%	5 71.4%	2 66.7%	3 50%	2 28.6%	6 50%	7 58.3%	1 33.3%
Non-evaluable	0 0%	1 33.3%	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%	0 0%

3. Secondary Outcome

Title	Summary of Disease Control Rate Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors
Description	Disease control rate (DCR) was defined as the sum of complete response (CR) and partial response (PR) rates, and stable disease (SD) rate for a minimum of 12 weeks. Complete response (CR) was defined as a disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to <10 mm. Partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions), taking as reference the smallest sum diameters while on study.
Time Frame	Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months

Outcome Measure Data

Analysis Population Description

Disease control rate was assessed in the Full Analysis Set.

Arm/Group Title	Part 1, Cohort 1: DS-2248 0.6 mg/m^2	Part 1, Cohort 2: DS-2248 1.2 mg/m^2	Part 1, Cohort 3: DS-2248 1.8 mg/m^2	Part 1, Cohort 4: DS-2248 2.7 mg/m^2	Part 1, Cohort 5: DS-2248 3.5 mg/m^2	Part 1, Cohort 6: DS-2248 4.5 mg/m^2	Part 1, Cohort 7: DS-2248 5.85 mg/m^2	Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-naive: DS-2248 4.5 mg/m^2
Arm/Group Description	Participants who received oral DS-2248 0.6 mg/m^2 once daily.	Participants who received oral DS-2248 1.2 mg/m^2 once daily.	Participants who received oral DS-2248 1.8 mg/m^2 once daily.	Participants who received oral DS-2248 2.7 mg/m^2 once daily.	Participants who received oral DS-2248 3.5 mg/m^2 once daily.	Participants who received oral DS-2248 4.5 mg/m^2 once daily.	Participants who received oral DS-2248 5.85 mg/m^2 once daily.	Participants who were epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK-inhibitor resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK treatment naive and received oral 4.5 mg/m^2 once daily.
Measure Participants	2	3	3	5	2	6	4	10	9	2
Count of Participants [Participants]	1 50%	0 0%	2 40%	0 0%	0 0%	1 16.7%	0 0%	2 16.7%	1 8.3%	1 33.3%

4. Secondary Outcome

Title	Duration of Stable Disease Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors
Description	Duration of response measured from the time at which criteria were first met for complete (CR) or partial response (PR) until the first date that progressive disease (PD) was objectively documented. Participants who had not progressed at the data cut-off date were censored at their last evaluable tumor assessment date. Duration of stable disease (SD) measured from the date of enrollment until the first date that criteria for disease progression were met. The minimum time interval for the duration of SD was 6 weeks. Participants who had not progressed at the data cut-off date were censored at their last evaluable tumor assessment date.
Time Frame	Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months

Outcome Measure Data

Analysis Population Description

Duration of stable disease was assessed in participants in which data were available in the Full Analysis Set.

Arm/Group Title	Part 1, Cohort 1: DS-2248 0.6 mg/m^2	Part 1, Cohort 2: DS-2248 1.2 mg/m^2	Part 1, Cohort 3: DS-2248 1.8 mg/m^2	Part 1, Cohort 4: DS-2248 2.7 mg/m^2	Part 1, Cohort 5: DS-2248 3.5 mg/m^2	Part 1, Cohort 6: DS-2248 4.5 mg/m^2	Part 1, Cohort 7: DS-2248 5.85 mg/m^2	Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-naive: DS-2248 4.5 mg/m^2
Arm/Group Description	Participants who received oral DS-2248 0.6 mg/m^2 once daily.	Participants who received oral DS-2248 1.2 mg/m^2 once daily.	Participants who received oral DS-2248 1.8 mg/m^2 once daily.	Participants who received oral DS-2248 2.7 mg/m^2 once daily.	Participants who received oral DS-2248 3.5 mg/m^2 once daily.	Participants who received oral DS-2248 4.5 mg/m^2 once daily.	Participants who received oral DS-2248 5.85 mg/m^2 once daily.	Participants who were epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK-inhibitor resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK treatment naive and received oral 4.5 mg/m^2 once daily.
Measure Participants	1	1	3	0	0	2	2	4	2	1
Median (Full Range) [weeks]	15.00	7.9	13.29	9.50	6.64	12.86	10.57	13.1

5. Secondary Outcome

Title	Summary of Progression-free Survival Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors
Description	Progression-free survival (PFS) defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of radiographic disease progression (as per RECIST V1.1) or death due to any cause. Participants who were alive with no objective documentation of (radiographic) disease progression by the data cut-off date were censored at the date of their last evaluable tumor assessment. Participants who were lost to follow-up or withdrew early from the study with no documented disease progression were censored at the last evaluable tumor assessment.
Time Frame	Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months

Outcome Measure Data

Analysis Population Description

Progression-free survival was assessed in the Full Analysis Set.

Arm/Group Title	Part 1, Cohort 1: DS-2248 0.6 mg/m^2	Part 1, Cohort 2: DS-2248 1.2 mg/m^2	Part 1, Cohort 3: DS-2248 1.8 mg/m^2	Part 1, Cohort 4: DS-2248 2.7 mg/m^2	Part 1, Cohort 5: DS-2248 3.5 mg/m^2	Part 1, Cohort 6: DS-2248 4.5 mg/m^2	Part 1, Cohort 7: DS-2248 5.85 mg/m^2	Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-naive: DS-2248 4.5 mg/m^2
Arm/Group Description	Participants who received oral DS-2248 0.6 mg/m^2 once daily.	Participants who received oral DS-2248 1.2 mg/m^2 once daily.	Participants who received oral DS-2248 1.8 mg/m^2 once daily.	Participants who received oral DS-2248 2.7 mg/m^2 once daily.	Participants who received oral DS-2248 3.5 mg/m^2 once daily.	Participants who received oral DS-2248 4.5 mg/m^2 once daily.	Participants who received oral DS-2248 5.85 mg/m^2 once daily.	Participants who were epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK-inhibitor resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK treatment naive and received oral 4.5 mg/m^2 once daily.
Measure Participants	2	3	3	5	2	6	4	10	9	2
Median (Full Range) [weeks]	10.93	5.71	13.29	7.00	5.64	6.00	6.57	7.21	7.14	10.00

6. Secondary Outcome

Title	Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve From Zero to Infinity Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors
Time Frame	Cycle 1, Day 1 predose, 0.5, 1, 2, 3, 4, 6, and 8 h postdose; Cycle 1, Day 2 and Day 15; Cycle 1, Day 8 predose, 1 and 6 h postdose; Cycle 2 and 3, Day 1, 8, and 15

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set for which data were available.

Arm/Group Title	Part 1, Cohort 1: DS-2248 0.6 mg/m^2	Part 1, Cohort 2: DS-2248 1.2 mg/m^2	Part 1, Cohort 3: DS-2248 1.8 mg/m^2	Part 1, Cohort 4: DS-2248 2.7 mg/m^2	Part 1, Cohort 5: DS-2248 3.5 mg/m^2	Part 1, Cohort 6: DS-2248 4.5 mg/m^2	Part 1, Cohort 7: DS-2248 5.85 mg/m^2	Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-naive: DS-2248 4.5 mg/m^2
Arm/Group Description	Participants who received oral DS-2248 0.6 mg/m^2 once daily.	Participants who received oral DS-2248 1.2 mg/m^2 once daily.	Participants who received oral DS-2248 1.8 mg/m^2 once daily.	Participants who received oral DS-2248 2.7 mg/m^2 once daily.	Participants who received oral DS-2248 3.5 mg/m^2 once daily.	Participants who received oral DS-2248 4.5 mg/m^2 once daily.	Participants who received oral DS-2248 5.85 mg/m^2 once daily.	Participants who were epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK-inhibitor resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK treatment naive and received oral 4.5 mg/m^2 once daily.
Measure Participants	1	3	3	1	1	5	3	9	5	1
Mean (Standard Deviation) [ng*h/mL]	76.47	122.56 (60.78)	186.16 (102.20)	362.31	356.01	675.57 (478.25)	837.50 (606.70)	501.21 (161.80)	645.62 (257.30)	459.96

7. Secondary Outcome

Title	Summary of Pharmacokinetic Parameter Maximum Concentration Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors
Time Frame	Cycle 1, Day 1 predose, 0.5, 1, 2, 3, 4, 6, and 8 h postdose; Cycle 1, Day 2 and Day 15; Cycle 1, Day 8 predose, 1 and 6 h postdose; Cycle 2 and 3, Day 1, 8, and 15

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set for which data were available.

Arm/Group Title	Part 1, Cohort 1: DS-2248 0.6 mg/m^2	Part 1, Cohort 2: DS-2248 1.2 mg/m^2	Part 1, Cohort 3: DS-2248 1.8 mg/m^2	Part 1, Cohort 4: DS-2248 2.7 mg/m^2	Part 1, Cohort 5: DS-2248 3.5 mg/m^2	Part 1, Cohort 6: DS-2248 4.5 mg/m^2	Part 1, Cohort 7: DS-2248 5.85 mg/m^2	Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-naive: DS-2248 4.5 mg/m^2
Arm/Group Description	Participants who received oral DS-2248 0.6 mg/m^2 once daily.	Participants who received oral DS-2248 1.2 mg/m^2 once daily.	Participants who received oral DS-2248 1.8 mg/m^2 once daily.	Participants who received oral DS-2248 2.7 mg/m^2 once daily.	Participants who received oral DS-2248 3.5 mg/m^2 once daily.	Participants who received oral DS-2248 4.5 mg/m^2 once daily.	Participants who received oral DS-2248 5.85 mg/m^2 once daily.	Participants who were epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK-inhibitor resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK treatment naive and received oral 4.5 mg/m^2 once daily.
Measure Participants	2	3	5	7	3	6	7	12	12	3
Mean (Standard Deviation) [ng/mL]	6.46 (1.54)	14.69 (7.37)	25.60 (9.62)	63.27 (31.02)	71.30 (37.99)	77.15 (32.17)	126.61 (67.60)	82.56 (34.22)	81.45 (53.71)	84.97 (34.16)

8. Secondary Outcome

Title	Summary of Pharmacokinetic Parameter Time at Maximum Concentration Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors
Time Frame	Cycle 1, Day 1 predose, 0.5, 1, 2, 3, 4, 6, and 8 h postdose; Cycle 1, Day 2 and Day 15; Cycle 1, Day 8 predose, 1 and 6 h postdose; Cycle 2 and 3, Day 1, 8, and 15

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set for which data were available.

Arm/Group Title	Part 1, Cohort 1: DS-2248 0.6 mg/m^2	Part 1, Cohort 2: DS-2248 1.2 mg/m^2	Part 1, Cohort 3: DS-2248 1.8 mg/m^2	Part 1, Cohort 4: DS-2248 2.7 mg/m^2	Part 1, Cohort 5: DS-2248 3.5 mg/m^2	Part 1, Cohort 6: DS-2248 4.5 mg/m^2	Part 1, Cohort 7: DS-2248 5.85 mg/m^2	Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-naive: DS-2248 4.5 mg/m^2
Arm/Group Description	Participants who received oral DS-2248 0.6 mg/m^2 once daily.	Participants who received oral DS-2248 1.2 mg/m^2 once daily.	Participants who received oral DS-2248 1.8 mg/m^2 once daily.	Participants who received oral DS-2248 2.7 mg/m^2 once daily.	Participants who received oral DS-2248 3.5 mg/m^2 once daily.	Participants who received oral DS-2248 4.5 mg/m^2 once daily.	Participants who received oral DS-2248 5.85 mg/m^2 once daily.	Participants who were epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK-inhibitor resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK treatment naive and received oral 4.5 mg/m^2 once daily.
Measure Participants	2	3	5	7	3	6	7	12	12	3
Mean (Standard Deviation) [hours]	2.0 (1.4)	1.7 (0.6)	1.1 (0.6)	1.5 (0.9)	1.2 (0.8)	2.3 (1.0)	2.1 (0.7)	1.8 (0.9)	1.6 (0.9)	2.0 (1.1)

9. Secondary Outcome

Title	Summary of Pharmacokinetic Parameter Terminal Half-life Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors
Time Frame	Cycle 1, Day 1 predose, 0.5, 1, 2, 3, 4, 6, and 8 h postdose; Cycle 1, Day 2 and Day 15; Cycle 1, Day 8 predose, 1 and 6 h postdose; Cycle 2 and 3, Day 1, 8, and 15

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set for which data were available.

Arm/Group Title	Part 1, Cohort 1: DS-2248 0.6 mg/m^2	Part 1, Cohort 2: DS-2248 1.2 mg/m^2	Part 1, Cohort 3: DS-2248 1.8 mg/m^2	Part 1, Cohort 4: DS-2248 2.7 mg/m^2	Part 1, Cohort 5: DS-2248 3.5 mg/m^2	Part 1, Cohort 6: DS-2248 4.5 mg/m^2	Part 1, Cohort 7: DS-2248 5.85 mg/m^2	Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-naive: DS-2248 4.5 mg/m^2
Arm/Group Description	Participants who received oral DS-2248 0.6 mg/m^2 once daily.	Participants who received oral DS-2248 1.2 mg/m^2 once daily.	Participants who received oral DS-2248 1.8 mg/m^2 once daily.	Participants who received oral DS-2248 2.7 mg/m^2 once daily.	Participants who received oral DS-2248 3.5 mg/m^2 once daily.	Participants who received oral DS-2248 4.5 mg/m^2 once daily.	Participants who received oral DS-2248 5.85 mg/m^2 once daily.	Participants who were epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK-inhibitor resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK treatment naive and received oral 4.5 mg/m^2 once daily.
Measure Participants	1	3	3	1	1	5	3	9	5	1
Mean (Standard Deviation) [hours]	9.58	7.81 (1.75)	8.11 (1.79)	10.78	8.57	8.62 (1.21)	10.05 (0.73)	9.94 (0.93)	9.23 (0.55)	6.76

10. Secondary Outcome

Title	Summary of Pharmacokinetic Parameter Total Body Clearance Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors
Time Frame	Cycle 1, Day 1 predose, 0.5, 1, 2, 3, 4, 6, and 8 h postdose; Cycle 1, Day 2 and Day 15; Cycle 1, Day 8 predose, 1 and 6 h postdose; Cycle 2 and 3, Day 1, 8, and 15

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set for which data were available.

Arm/Group Title	Part 1, Cohort 1: DS-2248 0.6 mg/m^2	Part 1, Cohort 2: DS-2248 1.2 mg/m^2	Part 1, Cohort 3: DS-2248 1.8 mg/m^2	Part 1, Cohort 4: DS-2248 2.7 mg/m^2	Part 1, Cohort 5: DS-2248 3.5 mg/m^2	Part 1, Cohort 6: DS-2248 4.5 mg/m^2	Part 1, Cohort 7: DS-2248 5.85 mg/m^2	Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-naive: DS-2248 4.5 mg/m^2
Arm/Group Description	Participants who received oral DS-2248 0.6 mg/m^2 once daily.	Participants who received oral DS-2248 1.2 mg/m^2 once daily.	Participants who received oral DS-2248 1.8 mg/m^2 once daily.	Participants who received oral DS-2248 2.7 mg/m^2 once daily.	Participants who received oral DS-2248 3.5 mg/m^2 once daily.	Participants who received oral DS-2248 4.5 mg/m^2 once daily.	Participants who received oral DS-2248 5.85 mg/m^2 once daily.	Participants who were epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK-inhibitor resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK treatment naive and received oral 4.5 mg/m^2 once daily.
Measure Participants	1	3	3	1	1	5	3	9	5	1
Mean (Standard Deviation) [L/h]	0.01	0.02 (0.01)	0.01 (0.00)	0.01	0.01	0.02 (0.01)	0.02 (0.01)	0.02 (0.00)	0.01 (0.00)	0.02

11. Secondary Outcome

Title	Summary of Drug Related Treatment Emergent Adverse Events Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors
Description	A treatment-emergent adverse event (TEAE) is defined as an adverse event that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pre-treatment state, when the AE is continuous. A DS-2248-related TEAE is an TEAE that is related to DS-2248 in the relationship.
Time Frame	Baseline up to 30 days post last dose, up to 2 years 11 months

Outcome Measure Data

Analysis Population Description

Treatment-emergent adverse events were assessed in the Safety Analysis Set.

Arm/Group Title	Part 1, Cohort 1: DS-2248 0.6 mg/m^2	Part 1, Cohort 2: DS-2248 1.2 mg/m^2	Part 1, Cohort 3: DS-2248 1.8 mg/m^2	Part 1, Cohort 4: DS-2248 2.7 mg/m^2	Part 1, Cohort 5: DS-2248 3.5 mg/m^2	Part 1, Cohort 6: DS-2248 4.5 mg/m^2	Part 1, Cohort 7: DS-2248 5.85 mg/m^2	Total - Part 1	Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-resistant: DS-2248 4.5 mg/m^2	Part 2, ALK-naive: DS-2248 4.5 mg/m^2	Total - Part 2
Arm/Group Description	Participants who received oral DS-2248 0.6 mg/m^2 once daily.	Participants who received oral DS-2248 1.2 mg/m^2 once daily.	Participants who received oral DS-2248 1.8 mg/m^2 once daily.	Participants who received oral DS-2248 2.7 mg/m^2 once daily.	Participants who received oral DS-2248 3.5 mg/m^2 once daily.	Participants who received oral DS-2248 4.5 mg/m^2 once daily.	Participants who received oral DS-2248 5.85 mg/m^2 once daily.	All participants who received oral DS-2248 in Part 1.	Participants who were epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK-inhibitor resistant and received oral 4.5 mg/m^2 once daily.	Participants who were ALK treatment naive and received oral 4.5 mg/m^2 once daily.	All participants who received oral DS-2248 in Part 2.
Measure Participants	2	3	5	7	3	6	7	33	12	12	3	27
Drug-related TEAEs	1 50%	0 0%	4 80%	5 71.4%	1 33.3%	4 66.7%	6 85.7%	21 175%	7 58.3%	9 300%	2 3.3%	18 NaN
Blood and Lymphatic Disorders	0 0%	0 0%	1 20%	1 14.3%	0 0%	0 0%	0 0%	2 16.7%	3 25%	1 33.3%	0 0%	4 NaN
Anaemia	0 0%	0 0%	1 20%	0 0%	0 0%	0 0%	0 0%	1 8.3%	3 25%	1 33.3%	0 0%	4 NaN
Thrombocytopenia	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	0 0%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Lymphopenia	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	1 NaN
Cardiac Disorders	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 14.3%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Tachycardia	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 14.3%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Eye Disorders	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	0 0%	1 8.3%	3 25%	2 66.7%	0 0%	5 NaN
Retinal haemorrhage	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	0 0%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Dry eye	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 16.7%	0 0%	0 0%	2 NaN
Photopsia	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	1 NaN
Vision blurred	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 8.3%	0 0%	0 0%	1 NaN
Vitreous floaters	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 66.7%	0 0%	2 NaN
Gastrointestinal Disorders	0 0%	0 0%	1 20%	3 42.9%	1 33.3%	1 16.7%	3 42.9%	9 75%	3 25%	4 133.3%	2 3.3%	9 NaN
Abdominal distension	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	0 0%	1 8.3%	0 0%	0 0%	1 1.7%	1 NaN
Anorectal discomfort	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Constipation	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	1 14.3%	2 16.7%	1 8.3%	0 0%	0 0%	1 NaN
Diarrhoea	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	1 8.3%	1 8.3%	3 100%	0 0%	4 NaN
Dyspepsia	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 14.3%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Flatulence	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	0 0%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Nausea	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 14.3%	1 8.3%	1 8.3%	2 66.7%	1 1.7%	4 NaN
Vomiting	0 0%	0 0%	1 20%	1 14.3%	0 0%	0 0%	1 14.3%	3 25%	0 0%	1 33.3%	1 1.7%	2 NaN
Abdominal pain	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	1 1.7%	2 NaN
Gastrooesophageal reflux disease	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	1 NaN
Paraesthesia oral	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	1 NaN
General Disorders & Administration Site Conditions	0 0%	0 0%	3 60%	1 14.3%	0 0%	2 33.3%	2 28.6%	8 66.7%	3 25%	3 100%	1 1.7%	7 NaN
Fatigue	0 0%	0 0%	3 60%	1 14.3%	0 0%	2 33.3%	2 28.6%	8 66.7%	3 25%	2 66.7%	1 1.7%	6 NaN
Oedema peripheral	0 0%	0 0%	1 20%	0 0%	0 0%	0 0%	0 0%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Irritability	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	1 NaN
Immune System Disorders	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	1 NaN
Hypersensitivity	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	1 NaN
Investigations	0 0%	0 0%	1 20%	1 14.3%	1 33.3%	2 33.3%	4 57.1%	9 75%	3 25%	3 100%	1 1.7%	7 NaN
Alanine aminotransferase increase	0 0%	0 0%	1 20%	0 0%	1 33.3%	0 0%	0 0%	2 16.7%	1 8.3%	0 0%	0 0%	1 NaN
Aspartate aminotransferase increased	0 0%	0 0%	1 20%	0 0%	0 0%	1 16.7%	1 14.3%	3 25%	0 0%	0 0%	0 0%	0 NaN
Blood alkaline phosphatase increased	0 0%	0 0%	0 0%	0 0%	1 33.3%	1 16.7%	0 0%	2 16.7%	0 0%	1 33.3%	0 0%	1 NaN
Blood creatinine increased	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	4 57.1%	5 41.7%	1 8.3%	0 0%	0 0%	1 NaN
Blood urea increased	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	1 14.3%	2 16.7%	0 0%	0 0%	0 0%	0 NaN
Blood uric acid increased	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Blood phosphorus increased	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 8.3%	1 33.3%	0 0%	2 NaN
Weight decreased	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	1 NaN
Weight increased	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.7%	1 NaN
Metabolism and Nutrition Disorders	1 50%	0 0%	1 20%	2 28.6%	0 0%	2 33.3%	2 28.6%	8 66.7%	3 25%	1 33.3%	2 3.3%	6 NaN
Decreased appetite	1 50%	0 0%	1 20%	0 0%	0 0%	1 16.7%	1 14.3%	4 33.3%	1 8.3%	0 0%	2 3.3%	3 NaN
Dehydration	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 8.3%	0 0%	0 0%	1 NaN
Hyperglycaemia	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	0 0%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Hyperphosphataemia	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Hyperuricaemia	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	1 14.3%	2 16.7%	0 0%	0 0%	0 0%	0 NaN
Hypoalbuminaemia	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 8.3%	0 0%	0 0%	1 NaN
Hypokalaemia	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	1 8.3%	0 0%	1 33.3%	0 0%	1 NaN
Musculoskeletal and Connective Tissue Disorders	0 0%	0 0%	1 20%	0 0%	0 0%	1 16.7%	0 0%	2 16.7%	1 8.3%	2 66.7%	0 0%	3 NaN
Arthralgia	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 8.3%	1 33.3%	0 0%	2 NaN
Muscular weakness	0 0%	0 0%	1 20%	0 0%	0 0%	1 16.7%	0 0%	2 16.7%	0 0%	0 0%	0 0%	0 NaN
Musculoskeletal pain	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	1 NaN
Myalgia	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	1 NaN
Nervous System Disorders	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	1 8.3%	2 16.7%	6 200%	1 1.7%	9 NaN
Dizziness	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 8.3%	2 66.7%	0 0%	3 NaN
Dysgeusia	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	1 8.3%	0 0%	5 166.7%	0 0%	5 NaN
Headache	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 8.3%	1 33.3%	1 1.7%	3 NaN
Nystagmus	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	1 NaN
Restless legs syndrome	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.7%	1 NaN
Renal and Urinary Disorders	0 0%	0 0%	1 20%	0 0%	0 0%	0 0%	1 14.3%	2 16.7%	0 0%	0 0%	0 0%	0 NaN
Proteinuria	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 14.3%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Renal failure acute	0 0%	0 0%	1 20%	0 0%	0 0%	0 0%	1 14.3%	2 16.7%	0 0%	0 0%	0 0%	0 NaN
Respiratory, Thoracic, and Mediastinal Disorders	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Dyspnoea	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Reproductive System and Breast Disorders	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.7%	1 NaN
Breast tenderness	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.7%	1 NaN
Skin and Subcutaneous Tissue Disorders	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 14.3%	1 8.3%	2 16.7%	1 33.3%	1 1.7%	4 NaN
Dry skin	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 8.3%	0 0%	0 0%	1 NaN
Hyperhidrosis	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 8.3%	0 0%	1 1.7%	2 NaN
Onychoclasis	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 14.3%	1 8.3%	0 0%	0 0%	0 0%	0 NaN
Pruritus	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 8.3%	1 33.3%	0 0%	2 NaN

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) were collected from baseline up to 30 days post last dose, up to 2 years 11 months.
Adverse Event Reporting Description	A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pre-treatment state, when the AE is continuous.
Arm/Group Title	Part 1, Cohort 1: DS-2248 0.6 mg/m^2		Part 1, Cohort 2: DS-2248 1.2 mg/m^2		Part 1, Cohort 3: DS-2248 1.8 mg/m^2		Part 1, Cohort 4: DS-2248 2.7 mg/m^2		Part 1, Cohort 5: DS-2248 3.5 mg/m^2		Part 1, Cohort 6: DS-2248 4.5 mg/m^2		Part 1, Cohort 7: DS-2248 5.85 mg/m^2		Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2		Part 2, ALK-resistant: DS-2248 4.5 mg/m^2		Part 2, ALK-naive: DS-2248 4.5 mg/m^2
Arm/Group Description	Participants who received oral DS-2248 0.6 mg/m^2 once daily.		Participants who received oral DS-2248 1.2 mg/m^2 once daily.		Participants who received oral DS-2248 1.8 mg/m^2 once daily.		Participants who received oral DS-2248 2.7 mg/m^2 once daily.		Participants who received oral DS-2248 3.5 mg/m^2 once daily.		Participants who received oral DS-2248 4.5 mg/m^2 once daily.		Participants who received oral DS-2248 5.85 mg/m^2 once daily.		Participants who were epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant and received oral 4.5 mg/m^2 once daily.		Participants who were ALK-inhibitor resistant and received oral 4.5 mg/m^2 once daily.		Participants who were ALK treatment naive and received oral 4.5 mg/m^2 once daily.
All Cause Mortality
	Part 1, Cohort 1: DS-2248 0.6 mg/m^2		Part 1, Cohort 2: DS-2248 1.2 mg/m^2		Part 1, Cohort 3: DS-2248 1.8 mg/m^2		Part 1, Cohort 4: DS-2248 2.7 mg/m^2		Part 1, Cohort 5: DS-2248 3.5 mg/m^2		Part 1, Cohort 6: DS-2248 4.5 mg/m^2		Part 1, Cohort 7: DS-2248 5.85 mg/m^2		Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2		Part 2, ALK-resistant: DS-2248 4.5 mg/m^2		Part 2, ALK-naive: DS-2248 4.5 mg/m^2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Serious Adverse Events
	Part 1, Cohort 1: DS-2248 0.6 mg/m^2		Part 1, Cohort 2: DS-2248 1.2 mg/m^2		Part 1, Cohort 3: DS-2248 1.8 mg/m^2		Part 1, Cohort 4: DS-2248 2.7 mg/m^2		Part 1, Cohort 5: DS-2248 3.5 mg/m^2		Part 1, Cohort 6: DS-2248 4.5 mg/m^2		Part 1, Cohort 7: DS-2248 5.85 mg/m^2		Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2		Part 2, ALK-resistant: DS-2248 4.5 mg/m^2		Part 2, ALK-naive: DS-2248 4.5 mg/m^2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		1/3 (33.3%)		2/5 (40%)		3/7 (42.9%)		1/3 (33.3%)		1/6 (16.7%)		1/7 (14.3%)		1/12 (8.3%)		0/12 (0%)		0/3 (0%)
Blood and lymphatic system disorders
Anaemia	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Thrombocytopenia	0/2 (0%)		0/3 (0%)		0/5 (0%)		1/7 (14.3%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Gastrointestinal disorders
Constipation	0/2 (0%)		1/3 (33.3%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
General disorders
Device occlusion	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Infections and infestations
Pneumonia	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Urinary tract infection	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Hypokalaemia	0/2 (0%)		0/3 (0%)		0/5 (0%)		1/7 (14.3%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Hyponatraemia	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Renal and urinary disorders
Renal failure acute	0/2 (0%)		1/3 (33.3%)		1/5 (20%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Urinary retention	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/2 (0%)		0/3 (0%)		0/5 (0%)		1/7 (14.3%)		1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Pulmonary embolism	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		1/12 (8.3%)		0/12 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Part 1, Cohort 1: DS-2248 0.6 mg/m^2		Part 1, Cohort 2: DS-2248 1.2 mg/m^2		Part 1, Cohort 3: DS-2248 1.8 mg/m^2		Part 1, Cohort 4: DS-2248 2.7 mg/m^2		Part 1, Cohort 5: DS-2248 3.5 mg/m^2		Part 1, Cohort 6: DS-2248 4.5 mg/m^2		Part 1, Cohort 7: DS-2248 5.85 mg/m^2		Part 2, EGFR TKI-resistant: DS-2248 4.5 mg/m^2		Part 2, ALK-resistant: DS-2248 4.5 mg/m^2		Part 2, ALK-naive: DS-2248 4.5 mg/m^2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		3/3 (100%)		5/5 (100%)		7/7 (100%)		3/3 (100%)		6/6 (100%)		7/7 (100%)		12/12 (100%)		10/12 (83.3%)		3/3 (100%)
Blood and lymphatic system disorders
Anaemia	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		1/3 (33.3%)		1/6 (16.7%)		0/7 (0%)		3/12 (25%)		1/12 (8.3%)		0/3 (0%)
Thrombocytopenia	0/2 (0%)		0/3 (0%)		0/5 (0%)		2/7 (28.6%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Cardiac disorders
Tachycardia	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		2/12 (16.7%)		0/3 (0%)
Eye disorders
Dry eye	0/2 (0%)		1/3 (33.3%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		1/6 (16.7%)		0/7 (0%)		2/12 (16.7%)		0/12 (0%)		0/3 (0%)
Vitreous floaters	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		2/12 (16.7%)		0/3 (0%)
Gastrointestinal disorders
Abdominal pain	1/2 (50%)		0/3 (0%)		1/5 (20%)		1/7 (14.3%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		2/12 (16.7%)		1/3 (33.3%)
Constipation	0/2 (0%)		1/3 (33.3%)		0/5 (0%)		3/7 (42.9%)		1/3 (33.3%)		2/6 (33.3%)		1/7 (14.3%)		2/12 (16.7%)		0/12 (0%)		1/3 (33.3%)
Diarrhoea	0/2 (0%)		0/3 (0%)		1/5 (20%)		1/7 (14.3%)		1/3 (33.3%)		0/6 (0%)		0/7 (0%)		1/12 (8.3%)		3/12 (25%)		0/3 (0%)
Dysphagia	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Gastrooesophageal reflux disease	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Nausea	0/2 (0%)		0/3 (0%)		1/5 (20%)		1/7 (14.3%)		0/3 (0%)		1/6 (16.7%)		1/7 (14.3%)		2/12 (16.7%)		2/12 (16.7%)		1/3 (33.3%)
Vomiting	0/2 (0%)		0/3 (0%)		2/5 (40%)		1/7 (14.3%)		0/3 (0%)		2/6 (33.3%)		1/7 (14.3%)		0/12 (0%)		2/12 (16.7%)		1/3 (33.3%)
General disorders
Fatigue	1/2 (50%)		1/3 (33.3%)		3/5 (60%)		4/7 (57.1%)		2/3 (66.7%)		4/6 (66.7%)		4/7 (57.1%)		5/12 (41.7%)		3/12 (25%)		1/3 (33.3%)
Non-cardiac chest pain	0/2 (0%)		0/3 (0%)		1/5 (20%)		1/7 (14.3%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		2/3 (66.7%)
Oedema peripheral	0/2 (0%)		1/3 (33.3%)		2/5 (40%)		2/7 (28.6%)		1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Pyrexia	2/2 (100%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Infections and infestations
Upper respiratory tract infection	1/2 (50%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		1/6 (16.7%)		0/7 (0%)		1/12 (8.3%)		0/12 (0%)		2/3 (66.7%)
Urinary tract infection	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Oral candidiasis	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		1/12 (8.3%)		0/12 (0%)		1/3 (33.3%)
Investigations
Alanine aminotransferase increased	0/2 (0%)		0/3 (0%)		2/5 (40%)		0/7 (0%)		1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Aspartate aminotransferase increased	0/2 (0%)		0/3 (0%)		2/5 (40%)		0/7 (0%)		0/3 (0%)		2/6 (33.3%)		1/7 (14.3%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Blood alkaline phosphatase increased	0/2 (0%)		0/3 (0%)		2/5 (40%)		2/7 (28.6%)		1/3 (33.3%)		3/6 (50%)		1/7 (14.3%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Blood creatinine increased	0/2 (0%)		0/3 (0%)		1/5 (20%)		1/7 (14.3%)		0/3 (0%)		0/6 (0%)		4/7 (57.1%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Blood lactate dehydrogenase increased	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Blood urea increased	0/2 (0%)		0/3 (0%)		0/5 (0%)		1/7 (14.3%)		0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Blood phosphorus increased	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		1/12 (8.3%)		1/12 (8.3%)		0/3 (0%)
Weight decreased	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		1/12 (8.3%)		1/12 (8.3%)		0/3 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/2 (50%)		0/3 (0%)		1/5 (20%)		1/7 (14.3%)		1/3 (33.3%)		1/6 (16.7%)		3/7 (42.9%)		2/12 (16.7%)		0/12 (0%)		2/3 (66.7%)
Hyperglycaemia	0/2 (0%)		0/3 (0%)		2/5 (40%)		1/7 (14.3%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Hyperuricaemia	0/2 (0%)		0/3 (0%)		0/5 (0%)		1/7 (14.3%)		0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Hypoalbuminaemia	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		1/3 (33.3%)		0/6 (0%)		1/7 (14.3%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Hypokalaemia	0/2 (0%)		0/3 (0%)		2/5 (40%)		1/7 (14.3%)		0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/12 (0%)		2/12 (16.7%)		0/3 (0%)
Hyponatraemia	0/2 (0%)		0/3 (0%)		1/5 (20%)		1/7 (14.3%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		2/12 (16.7%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		0/3 (0%)		2/6 (33.3%)		1/7 (14.3%)		1/12 (8.3%)		1/12 (8.3%)		0/3 (0%)
Musculoskeletal chest pain	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		1/3 (33.3%)		0/6 (0%)		0/7 (0%)		2/12 (16.7%)		0/12 (0%)		1/3 (33.3%)
Osteopenia	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Arthralgia	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		2/12 (16.7%)		2/12 (16.7%)		2/3 (66.7%)
Back pain	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		1/12 (8.3%)		1/12 (8.3%)		0/3 (0%)
Musculoskeletal pain	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		2/12 (16.7%)		0/3 (0%)
Pain in extremity	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		2/12 (16.7%)		1/12 (8.3%)		0/3 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	0/2 (0%)		2/3 (66.7%)		0/5 (0%)		1/7 (14.3%)		0/3 (0%)		0/6 (0%)		3/7 (42.9%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Nervous system disorders
Headache	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		2/6 (33.3%)		0/7 (0%)		2/12 (16.7%)		1/12 (8.3%)		2/3 (66.7%)
Neuropathy peripheral	0/2 (0%)		0/3 (0%)		1/5 (20%)		0/7 (0%)		1/3 (33.3%)		2/6 (33.3%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Dizziness	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		1/12 (8.3%)		2/12 (16.7%)		0/3 (0%)
Dysgeusia	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		5/12 (41.7%)		0/3 (0%)
Psychiatric disorders
Anxiety	0/2 (0%)		0/3 (0%)		1/5 (20%)		1/7 (14.3%)		0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Depression	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		1/3 (33.3%)		0/6 (0%)		1/7 (14.3%)		2/12 (16.7%)		0/12 (0%)		0/3 (0%)
Insomnia	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		1/12 (8.3%)		0/12 (0%)		1/3 (33.3%)
Renal and urinary disorders
Hematuria	0/2 (0%)		0/3 (0%)		2/5 (40%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Hydronephrosis	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		1/6 (16.7%)		1/7 (14.3%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Renal failure acute	0/2 (0%)		1/3 (33.3%)		1/5 (20%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/2 (50%)		0/3 (0%)		2/5 (40%)		1/7 (14.3%)		0/3 (0%)		1/6 (16.7%)		1/7 (14.3%)		4/12 (33.3%)		1/12 (8.3%)		0/3 (0%)
Dyspnoea	0/2 (0%)		2/3 (66.7%)		2/5 (40%)		0/7 (0%)		2/3 (66.7%)		1/6 (16.7%)		1/7 (14.3%)		4/12 (33.3%)		2/12 (16.7%)		0/3 (0%)
Dyspnoea exertional	0/2 (0%)		0/3 (0%)		1/5 (20%)		1/7 (14.3%)		0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Pleural effusion	0/2 (0%)		1/3 (33.3%)		1/5 (20%)		1/7 (14.3%)		1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/12 (0%)		0/12 (0%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Dry skin	0/2 (0%)		0/3 (0%)		1/5 (20%)		1/7 (14.3%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		1/12 (8.3%)		1/12 (8.3%)		0/3 (0%)
Hyperhidrosis	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		1/12 (8.3%)		0/12 (0%)		1/3 (33.3%)
Pruritus	0/2 (0%)		0/3 (0%)		0/5 (0%)		0/7 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		1/12 (8.3%)		1/12 (8.3%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

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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.