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

NCT03255083 | Terminated Phase 1 Results

• 1 other identifier: DS1205-A-U101
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 7

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 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)

Keywords

Oncology; Advanced Non-small Cell Lung Cancer; Inoperable Non-small Cell Lung Cancer; Metastatic; Non-resectable; Epidermal growth factor receptor; EGFR

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  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

  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

  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

  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

  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)

Study Arms (1)

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

Drug: DS-1205c; Drug: Osimertinib

Interventions

DS-1205c DRUG

DS-1205c 200 mg capsule

DS-1205c with osimertinib

Osimertinib DRUG

Osimertinib 80 mg tablet

DS-1205c with osimertinib

Eligibility Criteria

• Age: 18 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 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.
• 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.

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, 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.

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (7)

Taipei Medical University, Shuang Ho Hospital

New Taipei City, 23561, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng-Kung University Hospital

Tainan, 70457, Taiwan

Location

National Taiwan University Hospital

Taipei, 10048, Taiwan

Location

Taipei Medical University Hospital

Taipei, 11031, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Related Publications (2)

• 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.

  PMID: 19949011 BACKGROUND

• Yang 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.

  PMID: 36892745 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms; Neoplasm Metastasis

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

This study was terminated based on a business decision by the Sponsor.

Results Point of Contact

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

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical 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: August 17, 2017
• First Posted: August 21, 2017
• Study Start: April 10, 2019
• Primary Completion: September 4, 2020
• Study Completion: September 4, 2020
• Last Updated: January 19, 2022
• Results First Posted: January 11, 2022

Record last verified: 2022-01

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

TW (7)