Non-small Cell Lung Cancer (NSCLC)Phase 1NCT03255083
DS-1205c With Osimertinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer
A Phase 1 study testing DS-1205c and Osimertinib in people with Non-small Cell Lung Cancer (NSCLC), run by Daiichi Sankyo at 7 sites in Taiwan.
Trial summary
This study has two parts: dose escalation and dose expansion. The primary objectives are: For Dose Escalation, to assess the safety and tolerability of DS-1205c when combined with osimertinib in the study population and to determine the recommended dose for expansion of DS-1205c when combined with osimertinib in the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer (NSCLC)
- What is being tested?
- DS-1205c and Osimertinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 7 sitesTaiwan
- Study dates
- 10 Apr 2019to 4 Sep 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has histologically or cytologically documented adenocarcinoma NSCLC.
- Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation.
- Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011):
- Historical confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) or
- Has experienced clinical benefit from an EGFR TKI, followed by systemic progression (Response Evaluation Criteria in Solid Tumors [RECIST version 1.1] or World Health Organization [WHO]) while on continuous treatment with an EGFR TKI.
- Is currently receiving, and is able to discontinue erlotinib, gefinitib, or afatinib; or is currently receiving osimertinib at the prescribed 80 mg dose and is able to interrupt osimertinib.
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- Has been receiving erlotinib, gefitinib, or afatinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of screening period.
- Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib.
- Has at least one measurable lesion per RECIST version 1.1.
- Is willing to provide archival tumor tissue from a biopsy performed after progression during treatment with erlotinib, gefitinib, afatinib , or osimertinib OR has at least one lesion not previously irradiated, amenable to core biopsy, and is willing to undergo screening tumor biopsy.
- Demonstrates absence of EGFR T790M. No EGFR mutation testing is required if treated with osimertinib.
- Has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, with no deterioration over the previous 2 weeks.
Who cannot join
- Has any evidence of small cell histology, or combined small cell and non-small cell histology, in original tumor biopsy or in screening biopsy performed since progression.
- Has previously documented evidence of anaplastic lymphoma kinase (ALK) fusion, ROS proto-oncogene 1 (ROS1) fusion, BRAF V600E mutation, rearranged during transfection (RET) rearrangement, human epidermal growth factor receptor 2 (HER2) mutation, or MET exon 14 skipping mutation. No new testing for these genomic alterations is required for Screening.
- Has received treatment with any of the following:
- Any cytotoxic chemotherapy, immune checkpoint inhibitor therapy, investigational agent or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than EGFR TKI), within 14 days of the first dose of study treatment.
- Immune checkpoint inhibitor therapy within 30 days of first dose of study treatment.
- Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment.
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- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks, or palliative radiation therapy within 2 weeks of the first dose of study drug treatment.
- Has history of other active malignancy within 3 years prior to enrollment, except:
- Adequately treated non-melanoma skin cancer OR
- Superficial bladder tumors (tumor stage "a" [Ta], tumor stage "is" [Tis], tumor stage "1" [T1]) OR
- Curatively treated in situ disease OR
- Low risk non-metastatic prostate cancer (with Gleason score < 7, and following local treatment or undergoing active surveillance)
- Has spinal cord compression or clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (1 week for stereotactic radiotherapy).
- Presence of retinal disease in the eye that is not due to neovascular age-related macular degeneration (nAMD; eg, significant diabetic retinopathy, glaucomatous retinal atrophy, retinal detachment).
- Has history of myocardial infarction within the past 6 months.
- Has symptomatic congestive heart failure (New York Heart Association [NYHA] Classes II-IV), unstable angina, or cardiac arrhythmia requiring antiarrhythmic treatment.
- Has left ventricular ejection fraction (LVEF) <45% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
- Has any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, eg, complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval >250 milliseconds (ms).
- Has a mean QT interval corrected using Fridericia's correction (QTcF) prolongation >470 ms for females and >450 ms for males in three successive Screening measurements.
- Unable or unwilling to discontinue concomitant use of drugs that are known to prolong the QT interval.
- Has any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives.
- Has any history of interstitial lung disease (pulmonary fibrosis or severe radiation pneumonitis) or is suspected to have such disease by imaging during screening.
- Has history of pancreatitis within the past 6 months.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Taiwan7 sites
Taipei Medical University, Shuang Ho Hospital
New Taipei City, 23561
China Medical University Hospital
Taichung, 40447
Taichung Veterans General Hospital
Taichung, 40705
National Cheng-Kung University Hospital
Tainan, 70457
National Taiwan University Hospital
Taipei, 10048
Taipei Medical University Hospital
Taipei, 11031
Taipei Veterans General Hospital
Taipei, 11217
About this study
Official title: A Multicenter, Open-Label Phase 1 Study of DS-1205c in Combination With Osimertinib in Subjects With Metastatic or Unresectable EGFR-Mutant Non-Small Cell Lung Cancer
This study has two parts: dose escalation and dose expansion.
The primary objectives are:
Read more
- For Dose Escalation, to assess the safety and tolerability of DS-1205c when combined with osimertinib in the study population and to determine the recommended dose for expansion of DS-1205c when combined with osimertinib in the study population
- For Dose Expansion, to assess the safety and tolerability of DS-1205c when combined with osimertinib in the study population
In Dose Escalation, after a 7-day run in period (Cycle 0), there will be 21-day cycles (Cycle 1 onward). In Dose Expansion, there will be 21-day cycles.
The number of treatment cycles is not fixed in this study. Participants will continue study treatment until they decide not to (withdraw consent), their disease gets worse [progressive disease (PD)], or side effects become unacceptable (unacceptable toxicity).
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Being tested
- DS-1205c, Osimertinib
- Keywords
- Oncology, Advanced Non-small Cell Lung Cancer, Inoperable Non-small Cell Lung Cancer, Metastatic, Non-resectable, Epidermal growth factor receptor, EGFR
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DS-1205cDrug
DS-1205c 200 mg capsule
OsimertinibDrug
Osimertinib 80 mg tablet
| Study group | Role | What they receive |
|---|---|---|
| DS-1205c with osimertinib | Experimental | Participants receive DS-1205c (at planned doses given orally twice daily: 200 mg, 400 mg, 800 mg, 1200 mg) in combination with daily 80 mg oral dose of osimertinib Receives: Drug: DS-1205c; Drug: Osimertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Osimertinib
A dose-limiting toxicity (DLT) was defined as any TEAE not attributable to disease or disease-related processes that occurred during the DLT-evaluation period (Cycle 0, Day 1 to Cycle 1, Day 21 of Dose Escalation) and was Grade 3 or above, according to NCI-CTCAE Version 5.0.
Measured: Cycle 0, Day 1 (7-day cycle) to Cycle 1, Day 21 of Dose Escalation (each cycle was 21 days)
Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib
Treatment-emergent adverse events were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity after the initiating the study drug until 30 days after last dose of the study drug.
Measured: Screening; Cycle 0 (7-day cycle), Days -1, 1, 2, 4, 6, and 7; Cycle 1 (21-day cycle), Days 4, 8, and 15; Cycle 2 (21-day cycle), Days 1, 2, and 8; Cycle 3 and beyond (21-day cycles), Day 1; and end-of-treatment, 30 days after last dose, up to 1 year
Secondary outcomes (9)
Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib
Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Objective response rate is calculated as the number of participants with best objective response [complete response (CR) or partial response (PR) determined by Investigator assessment based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1], divided by the number of participants in the analysis population.
Measured: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
Disease Control Rate Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib
Disease control rate (DCR) is defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
Measured: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
Progression-free Survival Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib
Progression-free survival is defined as the time from the date of first dose to the earliest date of the first objective documentation of disease progression or death due to any cause. As per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions.
Measured: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
Overall Survival in Participants Following Administration of DS-1205c in Combination With Osimertinib
Overall survival was defined as the time from the date of first dose to the date of death due to any cause.
Measured: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib
The maximum concentration (Cmax) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
Measured: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib
The area under the plasma concentration curve from time 0 until last quantifiable time point (AUClast) and the area under the plasma concentration curve over a dosing interval (AUCtau) of DS-1205c alone and in combination with osimertinib were assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
Measured: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib
The time to maximum concentration (Tmax) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
Measured: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib
The trough plasma concentration (Ctrough) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
Measured: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib
The terminal half-life (t1/2) of DS-1205c alone and in combination with osimertinib was assessed. Pharmacokinetic (PK) parameters for each participant were estimated using non-compartmental analysis. Descriptive statistics are provided for all plasma concentration data by analyte/dose/study day/time and for each PK parameter by analyte/dose/study day, as appropriate.
Measured: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2017
- Study start10 Apr 2019
- Primary completion4 Sep 2020
- Study completion4 Sep 2020
Why it stopped: This study was terminated based on a business decision by the Sponsor.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung Cancer (NSCLC)Studies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03255083
- Sponsor's protocol ID
- DS1205-A-U101
- Status last verified
- Jan 2022
- First submitted
- 17 Aug 2017
- Last updated
- 19 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Publications
Jackman D, Pao W, Riely GJ, Engelman JA, Kris MG, Janne PA, Lynch T, Johnson BE, Miller VA. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol. 2010 Jan 10;28(2):357-60. doi: 10.1200/JCO.2009.24.7049. Epub 2009 Nov 30.
PubMed 19949011Yang JC, Su WC, Chiu CH, Shiah HS, Lee KY, Hsia TC, Uno M, Crawford N, Terakawa H, Chen WC, Takayama G, Hsu C, Hong Y, Saintilien C, McGill J, Chang GC. Evaluation of combination treatment with DS-1205c, an AXL kinase inhibitor, and osimertinib in metastatic or unresectable EGFR-mutant non-small cell lung cancer: results from a multicenter, open-label phase 1 study. Invest New Drugs. 2023 Apr;41(2):306-316. doi: 10.1007/s10637-023-01341-y. Epub 2023 Mar 9.
PubMed 36892745
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-Label Phase 1 Study of DS-1205c in Combination With Osimertinib in Subjects With Metastatic or Unresectable EGFR-Mutant Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT03255083
- Acronym / sponsor ID
- DS1205-A-U101
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Keywords
- Oncology, Advanced Non-small Cell Lung Cancer, Inoperable Non-small Cell Lung Cancer, Metastatic, Non-resectable, Epidermal growth factor receptor, EGFR
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated based on a business decision by the Sponsor.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- 10 Apr 2019 (actual)
- Primary completion
- 4 Sep 2020 (actual)
- Study completion
- 4 Sep 2020 (actual)
- First posted
- 21 Aug 2017 (actual)
- Results
- Posted 11 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study has two parts: dose escalation and dose expansion.
The primary objectives are:
- For Dose Escalation, to assess the safety and tolerability of DS-1205c when combined with osimertinib in the study population and to determine the recommended dose for expansion of DS-1205c when combined with osimertinib in the study population
- For Dose Expansion, to assess the safety and tolerability of DS-1205c when combined with osimertinib in the study population
In Dose Escalation, after a 7-day run in period (Cycle 0), there will be 21-day cycles (Cycle 1 onward). In Dose Expansion, there will be 21-day cycles.
The number of treatment cycles is not fixed in this study. Participants will continue study treatment until they decide not to (withdraw consent), their disease gets worse [progressive disease (PD)], or side effects become unacceptable (unacceptable toxicity).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DS-1205c with osimertinib | Experimental | Drug: DS-1205c, Drug: OsimertinibParticipants receive DS-1205c (at planned doses given orally twice daily: 200 mg, 400 mg, 800 mg, 1200 mg) in combination with daily 80 mg oral dose of osimertinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Has histologically or cytologically documented adenocarcinoma NSCLC.
- Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation.
- Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011):
- Is currently receiving, and is able to discontinue erlotinib, gefinitib, or afatinib; or is currently receiving osimertinib at the prescribed 80 mg dose and is able to interrupt osimertinib.
- Has been receiving erlotinib, gefitinib, or afatinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of screening period.
Key exclusion criteria (23 listed)
- Has any evidence of small cell histology, or combined small cell and non-small cell histology, in original tumor biopsy or in screening biopsy performed since progression.
- Has previously documented evidence of anaplastic lymphoma kinase (ALK) fusion, ROS proto-oncogene 1 (ROS1) fusion, BRAF V600E mutation, rearranged during transfection (RET) rearrangement, human epidermal growth factor receptor 2 (HER2) mutation, or MET exon 14 skipping mutation. No new testing for these genomic alterations is required for Screening.
- Has received treatment with any of the following:
- Has history of other active malignancy within 3 years prior to enrollment, except:
- Has spinal cord compression or clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (1 week for stereotactic radiotherapy).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DS-1205cDS-1205c 200 mg capsule | Drug | DS-1205c with osimertinib |
| OsimertinibOsimertinib 80 mg tablet | Drug | DS-1205c with osimertinib |
Primary outcome
Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Osimertinib
Time frame: Cycle 0, Day 1 (7-day cycle) to Cycle 1, Day 21 of Dose Escalation (each cycle was 21 days)
A dose-limiting toxicity (DLT) was defined as any TEAE not attributable to disease or disease-related processes that occurred during the DLT-evaluation period (Cycle 0, Day 1 to Cycle 1, Day 21 of Dose Escalation) and was Grade 3 or above, according to NCI-CTCAE Version 5.0.
Number of Participants With Treatment-emergent Adverse Events Occurring in More Than 1 Participant Following Administration With DS-1205c in Combination With Osimertinib
Time frame: Screening; Cycle 0 (7-day cycle), Days -1, 1, 2, 4, 6, and 7; Cycle 1 (21-day cycle), Days 4, 8, and 15; Cycle 2 (21-day cycle), Days 1, 2, and 8; Cycle 3 and beyond (21-day cycles), Day 1; and end-of-treatment, 30 days after last dose, up to 1 year
Treatment-emergent adverse events were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity after the initiating the study drug until 30 days after last dose of the study drug.
9 secondary outcomes
Number of Participants With Best Overall Response Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib
Time frame: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
Disease Control Rate Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib
Time frame: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
Progression-free Survival Assessed by Investigator Following Administration of DS-1205c in Combination With Osimertinib
Time frame: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
Overall Survival in Participants Following Administration of DS-1205c in Combination With Osimertinib
Time frame: Screening; Cycle 0 (7-day cycle); Cycle 1 and beyond (21-day cycles), Every 6 weeks (± 7 days) in the first 24 weeks after Day 1 of Cycle 1, and every 12 weeks (± 7 days) thereafter; and end-of-treatment, 30 days after last dose, up to 1 year
Maximum Concentration (Cmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib
Time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Area Under the Plasma Concentration Curve Following Administration of DS-1205c Alone and in Combination With Osimertinib
Time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Time to Maximum Concentration (Tmax) Following Administration of DS-1205c Alone and in Combination With Osimertinib
Time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Trough Plasma Concentration (Ctrough) Following Administration of DS-1205c Alone and in Combination With Osimertinib
Time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Terminal Half-life (t1/2) Following Administration of DS-1205c Alone and in Combination With Osimertinib
Time frame: Predose, 1, 2, 4, 6, 8, and 12 hours of Cycle 0 (7-day cycle; DS-1205c alone), Day 1; Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0, Day 7 (DS-1205c alone); Predose, 1, 2, 4, 6, 8, 10, and 12 hours of Cycle 2 (21-day cycle), Day 1 (DS-1205c+osimertinib)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19949011Jackman D, Pao W, Riely GJ, Engelman JA, Kris MG, Janne PA, Lynch T, Johnson BE, Miller VA. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol. 2010 Jan 10;28(2):357-60. doi: 10.1200/JCO.2009.24.7049. Epub 2009 Nov 30.
- Derived from this study: PubMed 36892745Yang JC, Su WC, Chiu CH, Shiah HS, Lee KY, Hsia TC, Uno M, Crawford N, Terakawa H, Chen WC, Takayama G, Hsu C, Hong Y, Saintilien C, McGill J, Chang GC. Evaluation of combination treatment with DS-1205c, an AXL kinase inhibitor, and osimertinib in metastatic or unresectable EGFR-mutant non-small cell lung cancer: results from a multicenter, open-label phase 1 study. Invest New Drugs. 2023 Apr;41(2):306-316. doi: 10.1007/s10637-023-01341-y. Epub 2023 Mar 9.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Leader study director
Daiichi Sankyo
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DS-1205c and Osimertinib in people with Non-small Cell Lung Cancer (NSCLC), run by Daiichi Sankyo at 7 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Osimertinib (time frame: Cycle 0, Day 1 (7-day cycle) to Cycle 1, Day 21 of Dose Escalation (each cycle was 21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03255083, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2022; AzTrials last refreshed its copy on 6 Nov 2026.