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



Status:Recruiting
Conditions:Lung Cancer, Lung Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:3/16/2019
Start Date:December 22, 2017
End Date:October 15, 2020

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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:

- 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 for 36 months unless they decide not to (withdraw consent), their disease gets
worse [progressive disease (PD)], or side effects become unacceptable (unacceptable
toxicity).


Inclusion Criteria:

1. Has histologically or cytologically documented adenocarcinoma NSCLC.

2. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or
radiation.

3. Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID:
19949011):

1. Historical confirmation that the tumor harbors an EGFR mutation known to be
associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R,
L861Q).

2. 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.

4. Is currently receiving and able to discontinue erlotinib, gefinitib, or afatinib.

5. 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.

6. Has radiological documentation of disease progression while receiving continuous
treatment with erlotinib, gefitinib, or afatinib.

7. Has at least one measurable lesion per RECIST version 1.1.

8. Is willing to provide archival tumor tissue from a biopsy performed within 6 months of
progression during treatment with erlotinib, gefitinib, or afatinib OR has at least
one lesion, not previously irradiated, amenable to core biopsy and is willing to
undergo screening tumor biopsy.

9. Demonstrates absence of EGFR T790M.

10. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with no
deterioration over the previous 2 weeks.

Exclusion Criteria:

1. 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.

2. Has previously documented evidence of ALK fusion, ROS1 fusion, BRAF V600E mutation,
RET rearrangement, HER2 mutation, MET amplification, or MET exon 14 skipping mutation.
No new testing for these genomic alterations is required for Screening.

3. Has received treatment with any of the following:

1. 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.

2. Immune checkpoint inhibitor therapy within 30 days of first dose of study
treatment.

3. Major surgery (excluding placement of vascular access) within 4 weeks of the
first dose of study treatment.

4. 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.

4. Has history of other active malignancy within 3 years prior to enrollment, except:

1. Adequately treated non-melanoma skin cancer OR

2. Superficial bladder tumors (Ta, Tis, T1) OR

3. Curatively treated in situ disease

5. 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).

6. 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).

7. Has history of myocardial infarction within the past 6 months.

8. Has symptomatic congestive heart failure (New York Heart Association [NYHA] Classes
II-IV), unstable angina, or cardiac arrhythmia requiring antiarrhythmic treatment.

9. Has left ventricular ejection fraction (LVEF) < 45% by either echocardiogram (ECHO) or
multigated acquisition (MUGA) scan.

10. 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).

11. Has a mean QTcF prolongation >470 ms for females and >450 ms for males in three
successive Screening measurements.

12. Unable or unwilling to discontinue concomitant use of drugs that are known to prolong
the QT interval.

13. 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.

14. Has any history of interstitial lung disease (pulmonary fibrosis or severe radiation
pneumonitis) or is suspected to have such disease by imaging during screening.
We found this trial at
3
sites
450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Phone: 617-632-3000
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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Boston, MA
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Grenoble, 38043
Phone: +33 476768708
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1275 York Ave
New York, New York 10021
(212) 639-2000
Phone: 212-639-2000
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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New York, NY
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