LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer

NCT01828099 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CLDK378A23012013-000319-26
• Study Type: interventional
• Target: 376
• Locations: 28 countries
• Sites: 164

Brief Summary

To compare the efficacy and safety of ceritinib with standard first-line chemotherapy (pemetrexed plus cisplatin or carboplatin) in patients with stage IIIB (not candidates for definitive multimodality therapy) or stage IV, non-squamous non-small cell lung cancer (NSCLC) harboring a confirmed anaplastic lymphoma kinase (ALK) rearrangement, using the Ventana immunohistochemistry (IHC) test.

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-Small Cell Lung Cancer; NSCLC; ALK; LDK378; Non-small cell lung carcinoma (NSCLC); treatment of lung cancer after first metastasis; lung cancer; lung adenocarcinoma; Non small cell lung carcinoma; Non small cell lung cancer; non-squamous non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC)

  PFS is defined as the time from the date of randomization to the date of the first radiologically documented disease progression (as assessed by BIRC per RECIST 1.1) or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or had received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. The distribution of PFS was estimated using the Kaplan-Meier (KM) method.

  From the date of randomization to the date of first radiologically documented disease progression or death due to any cause, up to approximately 34 months

Secondary Outcomes (24)

• Overall Survival (OS)

  From date of randomization to date of death due to any cause, up to approximately 120 months

• Overall Response Rate (ORR) by BIRC Assessment

  Up to approximately 34 months

• Overall Response Rate (ORR) by Investigator Assessment

  Up to approximately 120 months

• Duration of Response (DOR) by BIRC Assessment

  From first documented response to first documented disease progression or death, assessed up to approximately 34 months

• Duration of Response (DOR) by Investigator Assessment

  From first documented response to first documented disease progression or death, assessed up to approximately 120 months

Study Arms (2)

Ceritinib

EXPERIMENTAL

Ceritinib administered continuously through oral dosing at a dosage of 750 mg once daily in fasted state.

Drug: Ceritinib

Chemotherapy

ACTIVE COMPARATOR

Pemetrexed plus cisplatin or carboplatin (based on Investigator's choice) for 4 cycles (Induction) followed by pemetrexed as single agent (Maintenance)

Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin

Interventions

Ceritinib DRUG

Ceritinib was administered orally once-daily fasted at a dose of 750 mg capsules on a continuous dosing schedule.

Also known as: LDK378

Ceritinib

Pemetrexed DRUG

Pemetrexed was administered at a dose of 500 mg/m\^2 as an intravenous (iv) infusion on Day 1 of each 21-day cycle

Chemotherapy

Cisplatin DRUG

Cisplatin was administered by iv infusion at a dose of 75 mg/m\^2 every 21 days for up to 4 cycles.

Chemotherapy

Carboplatin DRUG

Carboplatin was administered as iv infusion (AUC 5-6) every 21 days up to 4 cycles

Chemotherapy

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient had a histologically or cytologically confirmed diagnosis of non-squamous Non-small cell lung cancer (NSCLC) that was Anaplastic lymphoma kinase (ALK) positive as assessed by the Ventana Immunohistochemistry (IHC) test. The test was performed at Novartis designated central laboratories.
• The patient had a newly diagnosed stage IIIB (who was not a candidate for definitive multimodality therapy) or stage IV NSCLC or relapsed locally advanced or metastatic NSCLC not previously treated with any systemic anti-cancer therapy (e.g. cytotoxic drugs, monoclonal antibody therapy, crizotinib or other ALK inhibitors, or other targeted therapies, either experimental or not), with the exception of neo-adjuvant or adjuvant therapy.
• The patient had at least one measurable lesion as defined by RECIST 1.1.

You may not qualify if:

• The patient had known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide, and magnesium stearate).
• The patient had a history of severe hypersensitivity reaction to platinum-containing drugs, pemetrexed, or any known excipients of these drugs.
• The patient had symptomatic central nervous system (CNS) metastases and was neurologically unstable or had required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (167)

Novartis Investigative Site

CABA, Buenos Aires, C1050AAK, Argentina

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CABA, Buenos Aires, C1180AAX, Argentina

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La Rioja, 5300, Argentina

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Woolloongabba, Queensland, 4102, Australia

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Heidelberg, Victoria, 3084, Australia

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Auckland, 92024, Australia

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Salzburg, 5020, Austria

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Vienna, 1210, Austria

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Fortaleza, Ceará, 60336-045, Brazil

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Salvador, Estado de Bahia, 40170-110, Brazil

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Recife, Pernambuco, 50070-550, Brazil

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Rio de Janiero, Rio de Janeiro, 20231-050, Brazil

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Natal, Rio Grande do Norte, 59075 740, Brazil

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Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

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Itajaí, Santa Catarina, 88301-229, Brazil

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Barretos, São Paulo, 14784 400, Brazil

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São José do Rio Preto, São Paulo, 15090 000, Brazil

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São Paulo, São Paulo, 01246-000, Brazil

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Guangzhou, Guangdong, 510080, China

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Changchun, Jilin, 130012, China

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Changchun, Jilin, 130021, China

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Shanghai, Shanghai Municipality, 200433, China

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Xi’an, Shanxi, 710038, China

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Chengdu, Sichuan, 610041, China

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Hangzhou, Zhejiang, 310003, China

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Hangzhou, Zhejiang, 310022, China

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Beijing, 100730, China

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Beijing, 101149, China

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Chongqing, 400037, China

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Chongqing, 400042, China

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Guang Dong Province, 510120, China

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Tianjin, 300052, China

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Bogota, Cundinamarca, 110111, Colombia

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Montería, 230004, Colombia

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Herlev, DK-2730, Denmark

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Odense C, DK 5000, Denmark

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Limoges, Haute Vienne, 87000, France

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Toulon, Val De Marne, 83800, France

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Caen, 14033, France

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Grenoble, 38043, France

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Lille, 59037, France

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Paris, 75475, France

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Pierre-Bénite, 69495, France

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Rennes, 35043, France

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Strasbourg, 67091, France

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Villejuif, 94800, France

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Cologne, 50937, Germany

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Coswig, 01640, Germany

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Essen, 45147, Germany

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Göttingen, 37075, Germany

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Großhansdorf, 22947, Germany

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Heidelberg, 69120, Germany

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Oldenburg, 26121, Germany

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Tübingen, 72076, Germany

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Ulm, 89081, Germany

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Wiesbaden, D-65199, Germany

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Athens, GR, 115 27, Greece

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Heraklion Crete, 71110, Greece

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Zalaegerszeg, Zala County, 8900, Hungary

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Budapest, 1121, Hungary

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Nyíregyháza, 4400, Hungary

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Veszprém, 8200, Hungary

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Hyderabad, Andhra Pradesh, 500 034, India

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Bangalore, Karnataka, 560 095, India

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Kochi, Kerala, 682 041, India

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Nashik, Maharashtra, 422 004, India

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New Delhi, National Capital Territory of Delhi, 110076, India

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Jaipur, Rajasthan, 302017, India

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Madurai, Tamil Nadu, 625107, India

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Vellore, Tamil Nadu, 632 004, India

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Kolkata, West Bengal, 700160, India

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Delhi, 110 085, India

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Mumbai, 400 012, India

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Dublin, DO4, Ireland

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Ancona, AN, 60126, Italy

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Bergamo, BG, 24125, Italy

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Genova, GE, 16132, Italy

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Monza, MB, 20900, Italy

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Milan, MI, 20132, Italy

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Milan, MI, 20141, Italy

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Milan, MI, 20162, Italy

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Rozzano, MI, 20089, Italy

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Perugia, PG, 06129, Italy

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Pisa, PI, 56124, Italy

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Aviano, PN, 33081, Italy

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Parma, PR, 43100, Italy

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Reggio Emilia, RE, 42123, Italy

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Roma, RM, 00152, Italy

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Roma, RM, 00189, Italy

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Orbassano, TO, 10043, Italy

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Udine, UD, 33100, Italy

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Napoli, 80131, Italy

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Nagoya, Aichi-ken, 464 8681, Japan

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Kashiwa, Chiba, 277 8577, Japan

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Akashi, Hyōgo, 673-8558, Japan

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Hirakata, Osaka, 573-1191, Japan

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Osaka, Osaka, 541-8567, Japan

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Koto Ku, Tokyo, 135 8550, Japan

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Niigata, 951 8520, Japan

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El Achrafiyé, 166830, Lebanon

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Saida, 652, Lebanon

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Guadalajara, Jalisco, 44280, Mexico

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Leiden, South Holland, 2333 ZA, Netherlands

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Amersfroort, 3818 ES, Netherlands

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Enschede, 7512 KZ, Netherlands

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Groningen, 9713 GZ, Netherlands

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Groningen, 9728 NZ, Netherlands

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Maastricht, 6229 HX, Netherlands

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Zoetermeer, NL-2722 EP, Netherlands

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Oslo, 0310, Norway

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Szczecin, 70-891, Poland

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Warsaw, 02 781, Poland

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Moscow, 115478, Russia

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Saint Petersburg, 197022, Russia

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Singapore, 119228, Singapore

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Singapore, 168583, Singapore

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Bundang Gu, Gyeonggi-do, 13620, South Korea

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Gyeonggi-do, Korea, 10408, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Granada, Andalusia, 18014, Spain

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Málaga, Andalusia, 29010, Spain

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Seville, Andalusia, 41013, Spain

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Seville, Andalusia, 41014, Spain

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Palma de Mallorca, Balearic Islands, 07120, Spain

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Barcelona, Catalonia, 08003, Spain

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Barcelona, Catalonia, 08035, Spain

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L'Hospitalet de Llobregat, Catalonia, 08907, Spain

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Lleida, Catalonia, 25198, Spain

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Mataró, Catalonia, 08301, Spain

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Reus, Catalonia, 43201, Spain

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Badajoz, Extremadura, 06080, Spain

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A Coruña, Galicia, 15006, Spain

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Lugo, Galicia, 27003, Spain

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Pamplona, Navarre, 31008, Spain

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Oviedo, Principality of Asturias, 33011, Spain

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San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320, Spain

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Alicante, Valencia, 03010, Spain

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Valencia, Valencia, 46014, Spain

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Barcelona, 08041, Spain

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Madrid, 28033, Spain

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Madrid, 28040, Spain

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Madrid, 28041, Spain

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Madrid, 28050, Spain

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Linköping, SE 581 85, Sweden

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Lund, 221 85, Sweden

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Stockholm, 171 76, Sweden

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Uppsala, 751 85, Sweden

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Kaohsiung City, 83301, Taiwan

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Taichung, 40447, Taiwan

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Taichung, 407219, Taiwan

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Taipei, 10002, Taiwan

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Taipei, 11217, Taiwan

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Taoyuan District, 33305, Taiwan

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Songkhla, Hat Yai, 90110, Thailand

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Khon Kaen, THA, 40002, Thailand

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Ankara, 06230, Turkey (Türkiye)

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Istanbul, 35100, Turkey (Türkiye)

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Exeter, Devon, EX2 5DW, United Kingdom

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Leeds, West Yorkshire, LS9 7TF, United Kingdom

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Birmingham, B9 5SS, United Kingdom

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London, NW1 2BU, United Kingdom

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Manchester, M20 2BX, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Related Publications (2)

• Soria JC, Tan DSW, Chiari R, Wu YL, Paz-Ares L, Wolf J, Geater SL, Orlov S, Cortinovis D, Yu CJ, Hochmair M, Cortot AB, Tsai CM, Moro-Sibilot D, Campelo RG, McCulloch T, Sen P, Dugan M, Pantano S, Branle F, Massacesi C, de Castro G Jr. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017 Mar 4;389(10072):917-929. doi: 10.1016/S0140-6736(17)30123-X. Epub 2017 Jan 24.

  PMID: 28126333 DERIVED

• Lin YT, Yu CJ, Yang JC, Shih JY. Anaplastic Lymphoma Kinase (ALK) Kinase Domain Mutation Following ALK Inhibitor(s) Failure in Advanced ALK Positive Non-Small-Cell Lung Cancer: Analysis and Literature Review. Clin Lung Cancer. 2016 Sep;17(5):e77-e94. doi: 10.1016/j.cllc.2016.03.005. Epub 2016 Mar 30.

  PMID: 27130468 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Adenocarcinoma of Lung

Interventions

ceritinib; Pemetrexed; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2013
• First Posted: April 10, 2013
• Study Start: July 9, 2013
• Primary Completion: June 24, 2016
• Study Completion: January 7, 2024
• Last Updated: January 16, 2025
• Results First Posted: September 21, 2017

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share

Locations

ES (24); AR (3); RU (2); JP (7); PL (2); CN (14); GR (2); CO (2); IN (11); SE (4); HU (4); AU (2); LE (2); TU (2); IT (18); DE (10); SG (2); TW (6); NL (7); DK (2); NO (1); KR (5); TH (4); GB (6); BR (10); FR (10); ME (1); IE (1)