Non Small Cell Lung CancerPhase 1NCT03599518

DS-1205c With Gefitinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer

A Phase 1 study testing DS-1205c and Gefitinib in people with Non Small Cell Lung Cancer, run by Daiichi Sankyo Co., Ltd. at 8 sites in Japan.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

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 gefitinib in the study population and to determine the recommended dose for expansion of DS-1205c when combined with gefitinib in the study… Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Non Small Cell Lung Cancer
What is being tested?: DS-1205c and Gefitinib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 8 sitesJapan
Study dates: 21 Sep 2018to 29 Jun 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 20 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 tyrosine kinase inhibitor (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 able to interrupt gefitinib or discontinue erlotinib, afatinib, or osimertinib

Show all 12Show fewer

Has been receiving gefitinib, erlotinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of screening period; participants who have been receiving gefitinib must be taking gefitinib at a dose of 250 mg/day
Has radiological documentation of disease progression while receiving continuous treatment with gefitinib, erlotinib, 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 gefitinib, erlotinib, 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 mutation in tumor tissue since progression during gefitinib, erlotinib, afatinib, or osimertinib treatment
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

Show all 23Show fewer

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 on antiandrogen therapy)
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).
Has 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 corrected QT interval 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 a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroid treatment, has current ILD/pneumonitis, or has suspected ILD/pneumonitis which cannot be ruled out by imaging at screening
Has history of pancreatitis within the past 6 months

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

Japan8 sites

The Cancer Institute Hospital of Japanese Foundation For Cancer Research
Ariake, Tokyo, 135-8550
Aichi Cancer Center
Chikusa, Aichi-ken, 464-8681
National Hospital Organization Kyushu Cancer Center
Fukuoka, 811-1347
Kyushu University Hospital
Fukuoka, 812-8582
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
Kindai University Hospital
Sayama, Osaka, 589-8511
Shizuoka Cancer Center
Shizuoka, 411-8777
National Cancer Center Hospital
Tsukiji, Tokyo, 104-0045

Other trials in Japan

About this study

Official title: A Multicenter, Open-Label Phase 1 Study of DS-1205c in Combination With Gefitinib 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:

For Dose Escalation, to assess the safety and tolerability of DS-1205c when combined with gefitinib in the study population and to determine the recommended dose for expansion of DS-1205c when combined with gefitinib in the study population
For Dose Expansion, to assess the safety and tolerability of DS-1205c when combined with gefitinib 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 for 36 months unless 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
Being tested: DS-1205c, Gefitinib
Medical subject headings: Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DS-1205cDrug
Also called Experimental product
DS-1205c 200 mg capsule for oral administration
GefitinibDrug
Gefitinib 250 mg tablet for oral administration

Study groups in NCT03599518
Study group	Role	What they receive
DS-1205c with Gefitinib	Experimental	Participants receive DS-1205c (at planned doses given orally twice daily: 200 mg, 400 mg, 800 mg, 1000 mg, 1200 mg) in combination with daily 250 mg oral dose of gefitinib Receives: Drug: DS-1205c; Drug: Gefitinib

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 Gefitinib
A dose-limiting toxicity (DLT) was defined as any treatment-emergent adverse event (TEAE) not attributable to disease or disease-related processes that occurs during the DLT-evaluation period (Cycle 0 Day 1 to Cycle 1 Day 21 of Dose Escalation) and is Grade 3 or above, according to NCI-CTCAE version 5.0.
Measured: Cycle 0 Day 1 (7-day cycle) to Cycle 1 Day 21 (each cycle is 21 days)
Number of Participants With Treatment-emergent Adverse Events Occurring in Participants Following Administration With DS-1205c in Combination With Gefitinib
An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A treatment-emergent adverse event (TEAE) was defined as an 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 37 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 1, 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 (8)

Number of Participants With Best Overall Response With Confirmation as Assessed by Investigator Following Administration of DS-1205c in Combination With Gefitinib
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 was calculated as the number of participants with best objective response (CR + PR) determined by Investigator assessment based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1].
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 Gefitinib
Disease control rate (DCR) was defined number of participants with CR+PR+SD objective response. 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 Gefitinib
Progression-free survival (PFS) was defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic PD 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 Gefitinib
Overall Survival (OS) was defined as the time from the date of first dose to the date of death from 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
Pharmacokinetic Parameter of Maximum Concentration (Cmax) of DS-1205a Following Administration of DS-1205c in Combination With Gefitinib
Blood samples for pharmacokinetic (PK) analyses of DS-1205a were obtained at specified time points. Plasma concentrations of DS-1205a were measured using validated assays and non-compartmental analysis.
Measured: Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0 (7-day cycle; DS-1205c alone), Days 1 and 7; Predose of Cycle 1 (21-day cycle), Day 1 (DS-1205c + gefitinib); Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 2 (21-day cycle; DS-1205c + gefitinib), Day 1
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of DS-1205a Following Administration of DS-1205c in Combination With Gefitinib
Blood samples for pharmacokinetic (PK) analyses of DS-1205a were obtained at specified time points. Plasma concentrations of DS-1205a were measured using validated assays and non-compartmental analysis.
Measured: Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0 (7-day cycle; DS-1205c alone), Days 1 and 7; Predose of Cycle 1 (21-day cycle), Day 1 (DS-1205c + gefitinib); Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 2 (21-day cycle; DS-1205c + gefitinib), Day 1
Pharmacokinetic Parameter Area Under the Plasma Concentration Curve of DS-1205a Following Administration of DS-1205c in Combination With Gefitinib
Blood samples for pharmacokinetic (PK) analyses of DS-1205a were obtained at specified time points. Plasma concentrations of DS-1205a were measured using validated assays and non-compartmental analysis. Area under the plasma concentration curve from time 0 to 8 hours (AUC8h), area under the plasma concentration-time curve from time 0 to 10 hours (AUC10h), and area under the plasma concentration-time curve during a dosing interval (AUCtau) were assessed.
Measured: Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0 (7-day cycle; DS-1205c alone), Days 1 and 7; Predose of Cycle 1 (21-day cycle), Day 1 (DS-1205c + gefitinib); Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 2 (21-day cycle; DS-1205c + gefitinib), Day 1
Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough) of DS-1205a Following Administration of DS-1205c in Combination With Gefitinib
Blood samples for pharmacokinetic (PK) analyses of DS-1205a were obtained at specified time points. Plasma concentrations of DS-1205a were measured using validated assays and non-compartmental analysis.
Measured: Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0 (7-day cycle; DS-1205c alone), Days 1 and 7; Predose of Cycle 1 (21-day cycle), Day 1 (DS-1205c + gefitinib); Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 2 (21-day cycle; DS-1205c + gefitinib), Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Sep 201829 Jun 2020

First posted26 Jul 2018
Study start21 Sep 2018
Primary completion22 Apr 2020
Study completion29 Jun 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 (1)Papers the sponsor has linked to this study.
Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
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: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03599518
Sponsor's protocol ID: DS1205-A-J102
Other IDs: 184026
Status last verified: May 2022
First submitted: 16 Jul 2018
Last updated: 8 Feb 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
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

Goto K, Shiraishi Y, Murakami H, Horinouchi H, Toyozawa R, Takeda M, Uno M, Crawford N, McGill J, Jimbo T, Ishigami M, Takayama G, Nakayama S, Ohwada S, Nishio M. Phase 1 study of DS-1205c combined with gefitinib for EGFR mutation-positive non-small cell lung cancer. Cancer Med. 2023 Mar;12(6):7090-7104. doi: 10.1002/cam4.5508. Epub 2023 Jan 9.
PubMed 36621830

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer

All Non Small Cell Lung Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Feb 2023. 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 Gefitinib in Subjects With Metastatic or Unresectable EGFR-Mutant Non-Small Cell Lung Cancer
ClinicalTrials.gov ID: NCT03599518
Acronym / sponsor ID: DS1205-A-J102
Conditions: Non Small Cell Lung Cancer
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: This study was terminated based on a business decision by the Sponsor.
Enrolment: 20 participants (actual)
Lead sponsor: Daiichi Sankyo Co., Ltd.Industry (pharma, biotech, devices)
Study start: 21 Sep 2018 (actual)
Primary completion: 22 Apr 2020 (actual)
Study completion: 29 Jun 2020 (actual)
First posted: 26 Jul 2018 (actual)
Results: Posted 8 Feb 2023

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 gefitinib in the study population and to determine the recommended dose for expansion of DS-1205c when combined with gefitinib in the study population
For Dose Expansion, to assess the safety and tolerability of DS-1205c when combined with gefitinib 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.

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 Gefitinib	Experimental	Drug: DS-1205c, Drug: GefitinibParticipants receive DS-1205c (at planned doses given orally twice daily: 200 mg, 400 mg, 800 mg, 1000 mg, 1200 mg) in combination with daily 250 mg oral dose of gefitinib

Who may qualify

Ages: 20 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 tyrosine kinase inhibitor (TKI) according to the Jackman criteria (PMID: 19949011):
Is currently receiving and able to interrupt gefitinib or discontinue erlotinib, afatinib, or osimertinib
Has been receiving gefitinib, erlotinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of screening period; participants who have been receiving gefitinib must be taking gefitinib at a dose of 250 mg/day

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-1205cAlso: Experimental productDS-1205c 200 mg capsule for oral administration	Drug	DS-1205c with Gefitinib
GefitinibGefitinib 250 mg tablet for oral administration	Drug	DS-1205c with Gefitinib

Primary outcome

Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Gefitinib
Time frame: Cycle 0 Day 1 (7-day cycle) to Cycle 1 Day 21 (each cycle is 21 days)
A dose-limiting toxicity (DLT) was defined as any treatment-emergent adverse event (TEAE) not attributable to disease or disease-related processes that occurs during the DLT-evaluation period (Cycle 0 Day 1 to Cycle 1 Day 21 of Dose Escalation) and is Grade 3 or above, according to NCI-CTCAE version 5.0.
Number of Participants With Treatment-emergent Adverse Events Occurring in Participants Following Administration With DS-1205c in Combination With Gefitinib
Time frame: Screening, Cycle 0 (7-day cycle), Days -1, 1, 2, 4, 6, and 7; Cycle 1 (21-day cycle), Days 1, 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
An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A treatment-emergent adverse event (TEAE) was defined as an 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 37 days after last dose of the study drug.

8 secondary outcomes

Number of Participants With Best Overall Response With Confirmation as Assessed by Investigator Following Administration of DS-1205c in Combination With Gefitinib
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 Gefitinib
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 Gefitinib
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 Gefitinib
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
Pharmacokinetic Parameter of Maximum Concentration (Cmax) of DS-1205a Following Administration of DS-1205c in Combination With Gefitinib
Time frame: Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0 (7-day cycle; DS-1205c alone), Days 1 and 7; Predose of Cycle 1 (21-day cycle), Day 1 (DS-1205c + gefitinib); Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 2 (21-day cycle; DS-1205c + gefitinib), Day 1
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of DS-1205a Following Administration of DS-1205c in Combination With Gefitinib
Time frame: Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0 (7-day cycle; DS-1205c alone), Days 1 and 7; Predose of Cycle 1 (21-day cycle), Day 1 (DS-1205c + gefitinib); Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 2 (21-day cycle; DS-1205c + gefitinib), Day 1
Pharmacokinetic Parameter Area Under the Plasma Concentration Curve of DS-1205a Following Administration of DS-1205c in Combination With Gefitinib
Time frame: Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0 (7-day cycle; DS-1205c alone), Days 1 and 7; Predose of Cycle 1 (21-day cycle), Day 1 (DS-1205c + gefitinib); Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 2 (21-day cycle; DS-1205c + gefitinib), Day 1
Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough) of DS-1205a Following Administration of DS-1205c in Combination With Gefitinib
Time frame: Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 0 (7-day cycle; DS-1205c alone), Days 1 and 7; Predose of Cycle 1 (21-day cycle), Day 1 (DS-1205c + gefitinib); Predose, 1, 2, 4, 6, 8, and 10 hours of Cycle 2 (21-day cycle; DS-1205c + gefitinib), Day 1

Results and safety

Results posted to the registry on 8 Feb 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
DS-1205c 200 mg + Gefitinib	5	0
DS-1205c 400 mg + Gefitinib	4	0
DS-1205c 800 mg + Gefitinib	6	0
DS-1205c 1000 mg + Gefitinib	1	0
DS-1205c 1200 mg + Gefitinib	4	0

Primary outcome: Number of Participants With Dose-limiting Toxicities (DLTs) Following Administration With DS-1205c in Combination With Gefitinib

Time frame: Cycle 0 Day 1 (7-day cycle) to Cycle 1 Day 21 (each cycle is 21 days). Count of participants. Unit: Participants

Measure	DS-1205c 200 mg + Gefitinib n = 4	DS-1205c 400 mg + Gefitinib n = 4	DS-1205c 800 mg + Gefitinib n = 6	DS-1205c 1000 mg + Gefitinib n = 1	DS-1205c 1200 mg + Gefitinib n = 4
Value	0	0	1	0	1

Population analysed: Dose-limiting toxicities (DLTs) were assessed in the DLT-Evaluable Set.

Primary outcome: Number of Participants With Treatment-emergent Adverse Events Occurring in Participants Following Administration With DS-1205c in Combination With Gefitinib

Time frame: Screening, Cycle 0 (7-day cycle), Days -1, 1, 2, 4, 6, and 7; Cycle 1 (21-day cycle), Days 1, 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. Count of participants. Unit: Participants

Measure	DS-1205c 200 mg + Gefitinib n = 5	DS-1205c 400 mg + Gefitinib n = 4	DS-1205c 800 mg + Gefitinib n = 6	DS-1205c 1200 mg + Gefitinib n = 4
Any TEAE	5	4	6	4
Infections and Infestations	2	1	0	1
Upper respiratory tract infection	1	0	0	1
Nasopharyngitis	0	1	0	0
Paronychia	1	0	0	0
Neoplasms Benign, Malignant, and Unspecified (including Cysts and Polyps)	1	1	1	0
Tumour pain	1	1	1	0
Blood and Lymphatic System Disorders	0	0	1	1

Population analysed: Adverse events (AEs) were assessed in the Safety Analysis Set.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment-emergent adverse events (TEAEs) were collected from Screening, Cycle 0 (7-day cycle), Days -1, 1, 2, 4, 6, and 7; Cycle 1 (21-day cycle), Days 1, 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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
DS-1205c 200 mg + Gefitinib	0 of 5 (0%)	5 of 5 (100%)	4 of 5
DS-1205c 400 mg + Gefitinib	0 of 4 (0%)	4 of 4 (100%)	1 of 4
DS-1205c 800 mg + Gefitinib	0 of 6 (0%)	6 of 6 (100%)	1 of 6
DS-1205c 1000 mg + Gefitinib	0 of 1 (0%)	0 of 1 (0%)	1 of 1
DS-1205c 1200 mg + Gefitinib	0 of 4 (0%)	4 of 4 (100%)	0 of 4

Limitations and caveats (from the sponsor): The sponsor decided to terminate the study at the end of the Dose Escalation part and the Dose Expansion part was not conducted.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36621830Goto K, Shiraishi Y, Murakami H, Horinouchi H, Toyozawa R, Takeda M, Uno M, Crawford N, McGill J, Jimbo T, Ishigami M, Takayama G, Nakayama S, Ohwada S, Nishio M. Phase 1 study of DS-1205c combined with gefitinib for EGFR mutation-positive non-small cell lung cancer. Cancer Med. 2023 Mar;12(6):7090-7104. doi: 10.1002/cam4.5508. Epub 2023 Jan 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/

Related trials for Non Small Cell Lung Cancer

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer

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.

Clinical Study Leader study director

Daiichi Sankyo

8 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 Gefitinib in people with Non Small Cell Lung Cancer, run by Daiichi Sankyo Co., Ltd. at 8 sites in Japan.

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 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Japan. 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 8 Feb 2023). 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 Gefitinib (time frame: Cycle 0 Day 1 (7-day cycle) to Cycle 1 Day 21 (each cycle is 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 NCT03599518, which also lists 1 linked publication.

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 8 Feb 2023.