LDK378 in Patients With ALK Positive NSCLC Previously Treated With Alectinib.

• ClinicalTrials.gov Identifier: NCT02450903
• Recruitment Status: Completed
• First Posted: May 21, 2015
• Results First Posted: December 24, 2020
• Last Update Posted: February 9, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

This was a single-arm, open-label, multicenter, phase II study to evaluate the efficacy and safety of the ALK inhibitor LDK378 when used as single agent in patients with ALK-rearranged stage IIIB or IV NSCLC previously treated with alectinib. Treatment with LDK378 750 mg qd continued until the patient experienced disease progression as determined by the investigator according to RECIST 1.1, unacceptable toxicity that precluded further treatment, pregnancy, start of a new anticancer therapy, discontinued treatment at the discretion of the patient or investigator, lost to follow-up, death, or study was terminated by Sponsor.

Condition or disease	Intervention/treatment	Phase
Non-Small-Cell Lung Cancer	Drug: LDK378	Phase 2

Detailed Description:

Study completed as per protocol. 'Switched to commercial drug' implies that after the primary and secondary objectives were achieved, one patient continued the study treatment as they did not meet the progression disease or AE to be discontinued from the treatment. But after the regulatory approval, Novartis decided to close the study, the 1 patient switched to commercially available drug.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Multi-center, Open-label, Single-Arm Study to Evaluate the Efficacy and Safety of Oral LDK378 Treatment for Patients With ALK-Positive Non-Small Cell Lung Cancer Previously Treated With Alectinib
• Actual Study Start Date: August 21, 2015
• Actual Primary Completion Date: July 31, 2017
• Actual Study Completion Date: May 24, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: LDK378 (Ceritinib); Participants who received LDK378 750mg once daily on a 28 day cycle.	Drug: LDK378; Oral LDK378 750mg once daily; Other Name: Oral LDK378 750mg once daily

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) to LDK378 by Investigator Assessment [ Time Frame: Until disease progression or unacceptable toxicity occurs, or patient withdrawal up to 798 days ]
   ORR, defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 by the investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Secondary Outcome Measures :

1. Disease Control Rate (DCR) [ Time Frame: 6 cycles of 28 days up to 798 days ]
   DCR, calculated as the percentage of participants with best overall response of CR, PR, or stable disease (SD) evaluated by investigator per RECIST 1.1; CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD); PD: taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
2. Time to Tumor Response (TTR) [ Time Frame: 6 cycles of 28 days up to 798 days ]
   TTR, calculated as the time from first dose of LDK378 to first documented response (CR or PR) evaluated by investigator per RECIST 1.1 for participants with confirmed PR or CR.
3. Duration of Response (DOR) [ Time Frame: 6 cycles of 28 days up to 798 days ]
   DOR, calculated as the time from the date of the first documented response (CR or PR) to the first documented disease progression evaluated by investigator per RECIST 1.1 or death due to any cause
4. Progression Free Survival (PFS) [ Time Frame: 6 cycles of 28 days up to 798 days ]
   PFS, calculated as the time from first dose of LDK378 to date of first documented disease progression evaluated by investigator per RECIST 1.1 or date of death due to any cause
5. Overall Survival (OS) [ Time Frame: 6 cycles of 28 days up to 798 days ]
   OS was defined as the time from the start date of study drug to the date of death due to any cause.
6. Overall Intracranial Response Rate (OIRR) [ Time Frame: 6 cycles of 28 days up to 798 days ]
   OIRR, calculated as the percentage of participants with a best overall confirmed response of CR or PR in the brain assessments for participants having measurable brain metastases at baseline

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of Stage IIIb or IV NSCLC that carries an ALK rearrangement as determined locally by Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test.
• Patients must have NSCLC that has progressed at study enrollment.
• Patients must have received previous treatment with alectinib for treatment of locally advanced or metastatic NSCLC. Prior therapy with crizotinib as ALK inhibitor therapy in addition to alectinib is allowed. Alectinib doesn't need to be the last therapy prior to study enrollment. No particular sequence of prior alectinib and crizotinib is required for enrollment.
• Patients must be chemotherapy-naïve or have received only one line of prior cytotoxic chemotherapy.
• Age 18 years or older at the time of informed consent.

Key Exclusion Criteria:

• Patients with known hypersensitivity to any of the excipients of LDK378.
• Prior therapy with other ALK inhibitor investigational agents except crizotinib and alectinib.
• Prior systemic anti-cancer (including investigational) therapy aside from alectinib, crizotinib and one regimen of previous cytotoxic chemotherapy for locally advanced or metastatic NSCLC.
• Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
• Patient with history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis.
• Patients with history of carcinomatous meningitis.
• Patient with a concurrent malignancy or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years.
• Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months)

Contacts and Locations

Locations

Japan

Novartis Investigative Site

Nagoya, Aichi, Japan, 464 8681

Novartis Investigative Site

Kashiwa, Chiba, Japan, 277 8577

Novartis Investigative Site

Fukuoka-city, Fukuoka, Japan, 811-1395

Novartis Investigative Site

Sakyo Ku, Kyoto, Japan, 606 8507

Novartis Investigative Site

Natori, Miyagi, Japan, 981-1293

Novartis Investigative Site

Okayama-city, Okayama, Japan, 700-8558

Novartis Investigative Site

Osaka Sayama, Osaka, Japan, 589 8511

Novartis Investigative Site

Chuo ku, Tokyo, Japan, 104 0045

Novartis Investigative Site

Koto ku, Tokyo, Japan, 135 8550

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Statistical Analysis Plan  [PDF] June 13, 2017

Study Protocol  [PDF] July 28, 2016

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hida T, Seto T, Horinouchi H, Maemondo M, Takeda M, Hotta K, Hirai F, Kim YH, Matsumoto S, Ito M, Ayukawa K, Tokushige K, Yonemura M, Mitsudomi T, Nishio M. Phase II study of ceritinib in alectinib-pretreated patients with anaplastic lymphoma kinase-rearranged metastatic non-small-cell lung cancer in Japan: ASCEND-9. Cancer Sci. 2018 Sep;109(9):2863-2872. doi: 10.1111/cas.13721. Epub 2018 Jul 25.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02450903
• Other Study ID Numbers: CLDK378A1201
• First Posted: May 21, 2015
• Results First Posted: December 24, 2020
• Last Update Posted: February 9, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Non-Small-Cell Lung Cancer; NSCLC; ALK; LDK378; alectinib; Non-small cell lung carcinoma (NSCLC); lung cancer; lung adenocarcinoma; Non small cell lung carcinoma; Non small cell lung cancer; Non-small cell lung cancer

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Ceritinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action