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

NCT03599518 | Terminated Phase 1 Results DMC

• 2 other identifiers: DS1205-A-J102184026
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 8

Brief 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 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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  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

  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

  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

  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

  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

Study Arms (1)

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

Drug: DS-1205c; Drug: Gefitinib

Interventions

DS-1205c DRUG

DS-1205c 200 mg capsule for oral administration

Also known as: Experimental product

DS-1205c with Gefitinib

Gefitinib DRUG

Gefitinib 250 mg tablet for oral administration

DS-1205c with Gefitinib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Daiichi Sankyo Co., Ltd.: lead

Study Sites (8)

Aichi Cancer Center

Chikusa, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

Kindai University Hospital

Sayama, Osaka, 589-8511, Japan

Location

The Cancer Institute Hospital of Japanese Foundation For Cancer Research

Ariake, Tokyo, 135-8550, Japan

Location

National Cancer Center Hospital

Tsukiji, Tokyo, 104-0045, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, 811-1347, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

Location

Related Publications (1)

• 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.

  PMID: 36621830 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gefitinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The sponsor decided to terminate the study at the end of the Dose Escalation part and the Dose Expansion part was not conducted.

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

Study Officials

• Clinical Study Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2018
• First Posted: July 26, 2018
• Study Start: September 21, 2018
• Primary Completion: April 22, 2020
• Study Completion: June 29, 2020
• Last Updated: February 8, 2023
• Results First Posted: February 8, 2023

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

JP (8)