DS-1205c With Gefitinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer
Study Details
Study Description
Brief Summary
This study has two parts: dose escalation and dose expansion.
The primary objectives are:
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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
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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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: DS-1205c with Gefitinib Participants receive DS-1205c (at planned doses given orally twice daily: 200 mg, 400 mg, 600 mg, 800 mg) in combination with daily 250 mg oral dose of gefitinib |
Drug: DS-1205c
DS-1205c 200 mg capsule for oral administration
Other Names:
Drug: Gefitinib
Gefitinib 250 mg tablet for oral administration
|
Outcome Measures
Primary Outcome Measures
- Number pf participants with dose-limiting toxicities during the Dose Escalation period [within 28 days]
- Number of participants with adverse events (AEs) [within 36 months]
An adverse event (AE) is 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
Secondary Outcome Measures
- Plasma concentration of DS-1205a versus time [during the 7 day run-in period]
- Maximum observed analyte concentration (Cmax) [during the 7 day run-in period]
- Actual sampling time to reach Cmax (Tmax) [during the 7 day run-in period]
- Area under the analyte concentration versus time curve during a dosing interval (AUCtau) [during the 7 day run-in period]
- Minimum observed analyte concentration prior to the beginning, or at the end, of a dosing interval (Ctrough) [during the 7 day run-in period]
- Cmax during a dosing interval (Tau) at steady state (Cmax,ss) [during the dose expansion period, within 36 months]
Categories: DS-1205a, gefitinib
- Plasma concentration of DS-1205a versus time [during the dose expansion period, within 36 months]
Categories: DS-1205a, gefitinib
- Tmax [during the dose expansion period, within 36 months]
Categories: DS-1205a, gefitinib
- Ctrough [during the dose expansion period, within 36 months]
Categories: DS-1205a, gefitinib
- AUCtau [during the dose expansion period, within 36 months]
Categories: DS-1205a, gefitinib
- Objective response rate (ORR), graded according to RECIST version 1.1 [within 36 months]
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.
- Change from baseline in size of target lesion(s) [within 36 months]
- Duration of response (DOR) [within 36 months]
DOR is defined as the time from documentation of tumor response [either CR or PR] to disease progression
- Disease control rate (DCR) [within 36 months]
DCR is defined as the sum of CR rate, PR rate, and stable disease (SD) rate
- Progression-free survival (PFS) [within 36 months]
PFS is 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
- Overall survival (OS) [within 36 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Has histologically or cytologically documented adenocarcinoma NSCLC
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Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation
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Has acquired resistance to EGFR tyrosine kinase inhibitor (TKI) according to the
Jackman criteria (PMID: 19949011):
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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
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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
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Is currently receiving and able to interrupt gefitinib or discontinue erlotinib, afatinib, or osimertinib
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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
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Has radiological documentation of disease progression while receiving continuous treatment with gefitinib, erlotinib, afatinib, or osimertinib
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Has at least one measurable lesion per RECIST version 1.1
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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
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Demonstrates absence of EGFR T790M mutation in tumor tissue since progression during gefitinib, erlotinib, afatinib, or osimertinib treatment
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Has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, with no deterioration over the previous 2 weeks
Exclusion Criteria:
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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
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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
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Has received treatment with any of the following:
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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
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Immune checkpoint inhibitor therapy within 30 days of first dose of study treatment
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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
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Has history of other active malignancy within 3 years prior to enrollment, except:
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Adequately treated non-melanoma skin cancer OR
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Superficial bladder tumors (Tumor stage "a" [Ta], Tumor stage "is" [Tis], Tumor stage "1" [T1]) OR
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Curatively treated in situ disease OR
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Low-risk non-metastatic prostate cancer (with Gleason score < 7 on antiandrogen therapy)
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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).
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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)
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Has history of myocardial infarction within the past 6 months
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Has symptomatic congestive heart failure [New York Heart Association (NYHA) Classes II-IV], unstable angina, or cardiac arrhythmia requiring antiarrhythmic treatment
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Has left ventricular ejection fraction (LVEF) < 45% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan
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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)
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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
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Unable or unwilling to discontinue concomitant use of drugs that are known to prolong the QT interval
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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
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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
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Has history of pancreatitis within the past 6 months
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aichi Cancer Center | Chikusa | Aichi | Japan | 464-8681 |
| 2 | National Cancer Center Hospital East | Kashiwa | Chiba | Japan | 277-8577 |
| 3 | Kindai University Hospital | Sayama | Osaka | Japan | 589-8511 |
| 4 | The Cancer Institute Hospital of Japanese Foundation For Cancer Research | Ariake | Tokyo | Japan | 135-8550 |
| 5 | National Cancer Center Hospital | Tsukiji | Tokyo | Japan | 104-0045 |
| 6 | National Hospital Organization Kyushu Cancer Center | Fukuoka | Japan | 811-1347 | |
| 7 | Kyushu University Hospital | Fukuoka | Japan | 812-8582 | |
| 8 | Shizuoka Cancer Center | Shizuoka | Japan | 411-8777 |
Sponsors and Collaborators
- Daiichi Sankyo Co., Ltd.
Investigators
- Study Director: Clinical Study Leader, Daiichi Sankyo, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DS1205-A-J102
- 184026