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Search / Trial NCT06875310

A Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)

Launched by MIRATI THERAPEUTICS INC. · Mar 7, 2025

Trial Information

Current as of April 26, 2025

Recruiting

Keywords

Immunotherapy Kras Kras G12 C Targeted Therapy

ClinConnect Summary

The KRYSTAL-4 trial is studying a new treatment approach for patients with a specific type of lung cancer called non-small cell lung cancer (NSCLC) that has a mutation known as KRAS G12C. This trial will compare a combination of three treatments—adagrasib, pembrolizumab, and chemotherapy—against a placebo (which looks like the real treatment but has no active ingredients) along with pembrolizumab and chemotherapy. The goal is to see which treatment works better in helping patients whose cancer has not been treated before and is either locally advanced or spread to other parts of the body.

To participate in this trial, you need to have a confirmed diagnosis of non-squamous NSCLC with the KRAS G12C mutation and measurable cancer that can be seen on scans. You should not have received any previous treatment for advanced cancer, and you must not be a candidate for more aggressive therapies like surgery. Participants can expect regular check-ups, tests to monitor their health, and to receive either the new treatment or the placebo during the study. This trial is currently recruiting patients aged 65 to 74 and is open to anyone, regardless of gender. If you have brain metastases (cancer that has spread to the brain), you may still be eligible as long as they are not causing symptoms and meet certain size criteria.

Gender

ALL

Eligibility criteria

  • Inclusion Criteria:
  • Histologically or cytologically confirmed diagnosis of non-squamous NSCLC with evidence of KRAS G12C mutation via tumor tissue and/or circulating tumor deoxyribonucleic acid (ctDNA).
  • Locally advanced or metastatic disease.
  • Measurable disease via computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1 criteria of at least 1 lesion.
  • No prior systemic anti-cancer therapy given for advanced or metastatic disease.
  • Not a candidate for definitive therapy (eg, chemoradiation or complete surgical resection).
  • Participants with brain metastases are eligible for enrollment, including those with untreated brain metastases. Brain metastases must be asymptomatic and not in need of immediate local therapy. Any untreated brain metastases must be ≤ 20 mm in diameter.
  • Any PD-L1 expression (0 to 100%) as determined by VENTANA PD-L1 (SP263) assay, Agilent PD-L1 IHC 22C3 pharmDx, or Agilent PD-L1 IHC 28-8 pharmDx.
  • Exclusion Criteria:
  • Participants with an active, known, prior documented, or suspected autoimmune or inflammatory disease.
  • Uncontrolled or significant cardiovascular conditions within 6 months prior to enrollment.
  • Inadequate bone marrow or liver function or electrocardiogram (ECG) abnormalities.
  • Ongoing treatment with concomitant medication known to cause prolonged QTc interval and that cannot be switched to alternative treatment prior to study entry.
  • Treatment targeting KRAS G12C mutation (eg, sotorasib, adagrasib) in any setting.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration.
  • Other protocol-defined Inclusion/Exclusion criteria apply.

About Mirati Therapeutics Inc.

Mirati Therapeutics, Inc. is a biopharmaceutical company dedicated to discovering and developing transformative therapies for patients with genetically defined cancers. With a strong focus on precision medicine, Mirati leverages advanced science and innovative technologies to identify and target specific genetic mutations driving cancer progression. The company’s robust pipeline includes novel small molecules and immunotherapies, aimed at addressing significant unmet medical needs and improving patient outcomes. Committed to advancing oncology research, Mirati collaborates with healthcare professionals and research institutions to bring cutting-edge treatments from the lab to the clinic.

Locations

Frankston, Victoria, Australia

Elizabeth Vale, South Australia, Australia

Joondalup, Western Australia, Australia

Tainan City, Tainan, Taiwan

Liège, , Belgium

New Taipei, , Taiwan

London, London, City Of, United Kingdom

Ciudad De Buenos Aires, Buenos Aires, Argentina

Austin, Texas, United States

Seattle, Washington, United States

Ciudad Autónoma De Buenos Aires, Buenos Aires, Argentina

Ciudad De Buenos Aires, Buenos Aires, Argentina

Pilar, Buenos Aires, Argentina

Abb, Ciudad Autónoma De Buenos Aires, Argentina

Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina

Caba, Ciudad Autónoma De Buenos Aires, Argentina

Río Cuarto, Córdoba, Argentina

Rosario, Santa Fe, Argentina

Canberra, Australian Capital Territory, Australia

North Tamworth, New South Wales, Australia

Orange, New South Wales, Australia

Brisbane, Queensland, Australia

Elizabeth Vale, South Australia, Australia

Frankston, Victoria, Australia

Melbourne, Victoria, Australia

Traralgon, Victoria, Australia

Joondalup, Western Australia, Australia

Wels, Oberösterreich, Austria

Graz, Steiermark, Austria

Linz, , Austria

Wien, , Austria

Brussels, Bruxelles Capitale, Région De, Belgium

Brussels, Bruxelles Capitale, Région De, Belgium

Hasselt, Limburg, Belgium

Gent, Oost Vlaanderen, Belgium

Leuven, Vlaams Brabant, Belgium

Salvador, Bahia, Brazil

Vitória, Espírito Santo, Brazil

Belo Horizonte, Minas Gerais, Brazil

Ijui, Rio Grande Do Sul, Brazil

Porto Alegre, Rio Grande Do Sul, Brazil

Santa Cruz Do Sul, Rio Grande Do Sul, Brazil

Porto Velho, Rondonia, Brazil

Blumenau, Santa Catarina, Brazil

Itajaí, Santa Catarina, Brazil

Barretos, São Paulo, Brazil

Sao Paulo, São Paulo, Brazil

São Carlos, São Paulo, Brazil

São José Do Rio Preto, São Paulo, Brazil

Rio De Janeiro, , Brazil

São Paulo, , Brazil

Halifax, Nova Scotia, Canada

Montreal, Quebec, Canada

Santiago, Región Metropolitana De Santiago, Chile

Santiago, Región Metropolitana De Santiago, Chile

Bengbu, Anhui, China

Hefei, Anhui, China

Beijing, Beijing, China

Beijing, Beijing, China

Beijing, Beijing, China

Beijing, Beijing, China

Chongqing, Chongqing, China

Fuzhou Fujian, Fujian, China

Xiamen, Fujian, China

Guangzhou, Guangdong, China

Shantou, Guangdong, China

Shenzhen, Guangdong, China

Shenzhen, Guangdong, China

Nanning, Guangxi, China

Shijiazhuang, Hebei, China

Harbin, Heilongjiang, China

Xinxiang, Henan, China

Wuhan, Hubei, China

Wuhan, Hubei, China

Changsha, Hunan, China

Nanjing, Jiangsu, China

Suzhou, Jiangsu, China

Yangzhou, Jiangsu, China

Nanchang, Jiangxi, China

Changchun, Jilin, China

Shenyang, Liaoning, China

Shenyang, Liaoning, China

Shenyang, Liaoning, China

Jinan, Shandong, China

Linyi, Shandong, China

Shanghai, Shanghai, China

Shanghai, Shanghai, China

Taiyuan, Shanxi, China

Cheng Du, Sichuan, China

Tianjin, Tianjin, China

Hangzhou, Zhejiang, China

Hangzhou, Zhejiang, China

Hangzhou, Zhejiang, China

Linhai, Zhejiang, China

Shanghai, , China

Medellín, Antioquia, Colombia

Rionegro, Antioquia, Colombia

Puerto Colombia, Atlántico, Colombia

Valledupar, Cesar, Colombia

Montería, Córdoba, Colombia

Bogotá, Distrito Capital De Bogotá, Colombia

Floridablanca, Santander, Colombia

Floridablanca, Santander, Colombia

Cali, Valle Del Cauca, Colombia

Mulhouse, Alsace, France

Caen, Calvados, France

Brest, Finistère, France

Montpellier, Hérault, France

La Tronche, Isère, France

Saint Herblain, Loire Atlantique, France

Angers, Maine Et Loire, France

Vandoeuvre Lès Nancy, Meurthe Et Moselle, France

Amiens, Somme, France

Villejuif, Val De Marne, France

Clermont Ferrand, , France

Marseille, , France

Paris, , France

Paris, , France

Saint Mandé, , France

Boulogne Billancourt, île De France, France

Esslingen, Baden Württemberg, Germany

Kempten, Bayern, Germany

München, Bayern, Germany

München, Bayern, Germany

Frankfurt, Hessen, Germany

Gießen, Hessen, Germany

Hannover, Niedersachsen, Germany

Oldenburg, Niedersachsen, Germany

Herne, Nordrhein Westfalen, Germany

Köln, Nordrhein Westfalen, Germany

Halle, Sachsen Anhalt, Germany

Halle, Sachsen Anhalt, Germany

Lostau, Sachsen Anhalt, Germany

Gera, Thüringen, Germany

Jena, Thüringen, Germany

Berlin, , Germany

Berlin, , Germany

Heidelberg, , Germany

Hemer, , Germany

Stuttgart, , Germany

Wuerzburg, , Germany

Hksar, , Hong Kong

Hksar, , Hong Kong

Gyöngyös, Heves, Hungary

Tatabánya, Komárom Esztergom, Hungary

Farkasgyepu, Veszprém, Hungary

Budapest, , Hungary

Budapest, , Hungary

Visakhapatnam, Andhra Pradesh, India

New Delhi, Delhi, India

New Delhi, Delhi, India

New Delhi, Delhi, India

Ahmedabad, Gujarat, India

Ahmedabad, Gujarat, India

Thiruvananthapuram, Kerala, India

Aurangabad, Maharashtra, India

Mumbai, Maharashtra, India

Bhubaneswar, Odisha, India

Madurai, Tamil Nadu, India

Hyderabad, Telangana, India

Hyderabad, Telangana, India

Varanasi, Uttar Pradesh, India

Howrah, West Bengal, India

Kolkata, West Bengal, India

Cork, , Ireland

Dublin, , Ireland

Dublin, , Ireland

Dublin, , Ireland

Dublin, , Ireland

Jerusalem, Yerushalayim, Israel

Meldola, Emilia Romagna, Italy

Naples, Napoli, Italy

Orbassano, Piemonte, Italy

Bari, Puglia, Italy

Rome, Roma, Italy

Firenze, Toscana, Italy

Perugia, Umbria, Italy

Padova, , Italy

Parma, , Italy

Pavia, , Italy

Varese, , Italy

Nagoya, Aichi, Japan

Sapporo, Hokkaido, Japan

Kanazawa, Ishikawa, Japan

Sagamihara, Kanagawa, Japan

Yokohama, Kanagawa, Japan

Sendai, Miyagi, Japan

Kashihara, Nara, Japan

Kurashiki, Okayama, Japan

Hidaka, Saitama, Japan

Ina Machi, Saitama, Japan

Shimotsuga, Tochigi, Japan

Toyoma, Toyama, Japan

Iwakuni, Yamaguchi, Japan

Akashi, , Japan

Aomori, , Japan

Fukuoka, , Japan

Fukushima, , Japan

Kumamoto, , Japan

Osaka, , Japan

Osaka, , Japan

Cheongju Si, Chungcheongbuk Do [Chungbuk], Korea, Republic Of

Namdong Gu, Incheon Gwangyeoksi [Incheon], Korea, Republic Of

Yangsan, Kyǒngsangnam Do, Korea, Republic Of

Busan, Pusan Kwangyǒkshi, Korea, Republic Of

Seoul, Seoul Teukbyeolsi [Seoul], Korea, Republic Of

Seoul, Seoul Teukbyeolsi [Seoul], Korea, Republic Of

Seoul, Seoul Teukbyeolsi [Seoul], Korea, Republic Of

Seoul, Seoul Teukbyeolsi [Seoul], Korea, Republic Of

Saltillo, Coahuila, Mexico

Mexico City, Distrito Federal, Mexico

Pachuca, Hidalgo, Mexico

Guadalajara, Jalisco, Mexico

Guadalajara, Jalisco, Mexico

Monterrey, Nuevo León, Mexico

Chihuahua, , Mexico

Puebla, , Mexico

Veracruz, , Mexico

Wrocław, Dolnośląskie, Poland

Lublin, Lubelskie, Poland

Gorlice, Małopolskie, Poland

Kraków, Małopolskie, Poland

Prabuty, Pomorskie, Poland

Poznan, Wielkopolskie, Poland

Bydgoszcz, , Poland

Katowice, , Poland

Lisbon, Lisboa, Portugal

Coimbra, , Portugal

Porto, , Portugal

Bucharest, București, Romania

Bucharest, București, Romania

Cluj Napoca, Cluj, Romania

Florești, Cluj, Romania

Constanta, Constanța, Romania

Ovidiu, Constanța, Romania

Craiova, Dolj, Romania

Ploiești, Prahova, Romania

Timișoara, Timiș, Romania

Cluj, , Romania

Cluj, , Romania

Constanța, , Romania

Iași, , Romania

Iași, , Romania

Riyadh, , Saudi Arabia

Riyadh, , Saudi Arabia

A Coruña, A Coruña [La Coruña], Spain

Santiago De Compostela, A Coruña [La Coruña], Spain

Barcelona, Barcelona [Barcelona], Spain

Hospitalet, Barcelona [Barcelona], Spain

Barcelona, Catalunya [Cataluña], Spain

Palma, Illes Balears [Islas Baleares], Spain

Madrid, Madrid, Comunidad De, Spain

Madrid, Madrid, Comunidad De, Spain

Madrid, Madrid, Comunidad De, Spain

Majadahonda, Madrid, Comunidad De, Spain

Madrid, , Spain

Málaga, , Spain

Sevilla, , Spain

València, , Spain

St.Gallen, Sankt Gallen, Switzerland

Münsterlingen, , Switzerland

Tainan City, Tainan, Taiwan

New Taipei, , Taiwan

Tainan, , Taiwan

Taipei, , Taiwan

Muang, Khon Kaen, Thailand

Bangkok, Krung Thep Maha Nakhon, Thailand

Hatyai, Songkhla, Thailand

Stanbul, İstanbul, Turkey

Izmir, Karsiyaka, İzmir, Turkey

Adana, , Turkey

Ankara, , Turkey

Ankara, , Turkey

Ankara, , Turkey

Istanbul, , Turkey

Izmir, , Turkey

Malatya, , Turkey

London, London, City Of, United Kingdom

Birmingham, , United Kingdom

Guildford, , United Kingdom

Guildford, , United Kingdom

Manchester, , United Kingdom

North Tamworth, New South Wales, Australia

Birmingham, Alabama, United States

Fullerton, California, United States

Long Beach, California, United States

Newport Beach, California, United States

Orange, California, United States

Santa Barbara, California, United States

Denver, Colorado, United States

Gainesville, Florida, United States

Palm Bay, Florida, United States

Tamarac, Florida, United States

Tampa, Florida, United States

Fort Eisenhower, Georgia, United States

Marietta, Georgia, United States

Arlington Heights, Illinois, United States

Munster, Indiana, United States

Edgewood, Kentucky, United States

Louisville, Kentucky, United States

Shreveport, Louisiana, United States

Columbia, Maryland, United States

Boston, Massachusetts, United States

Worcester, Massachusetts, United States

White Plains, New York, United States

Asheville, North Carolina, United States

Columbus, Ohio, United States

York, Pennsylvania, United States

Greenville, South Carolina, United States

Laredo, Texas, United States

San Antonio, Texas, United States

Panagyurishte, Pazardzhik, Bulgaria

Sofia, Sofia (Stolitsa), Bulgaria

Ruse, , Bulgaria

Stara Zagora, , Bulgaria

Guangzhou, Guangdong, China

Nanyang, Henan, China

Chengdu, Sichuan, China

Medellín, Antioquia, Colombia

Montería, Cor, Colombia

Dubrovnik, Dubrovačko Neretvanska županija, Croatia

Rijeka, Primorsko Goranska županija, Croatia

Split, Splitsko Dalmatinska županija, Croatia

Osijek, , Croatia

Zagreb, , Croatia

Dijon, Côte D'or, France

Marseille, Provence Alpes Côte D'azur, France

Limoges, , France

Flensburg, Schleswig Holstein, Germany

Athens, Attikí, Greece

Athens, Attikí, Greece

Larissa, Thessalía, Greece

Gyor, Győr Moson Sopron, Hungary

Kaposvár, Somogy, Hungary

Hyderabad, Telangana, India

Hyderabad, , India

Petah Tikva, Hamerkaz, Israel

Ramat Gan, Hamerkaz, Israel

Zerifin, Hamerkaz, Israel

Haifa, ḥeifā, Israel

Genova, , Italy

Nagoya, Aichi, Japan

Hirakata, Osaka, Japan

Hamamatsu, Shizuoka, Japan

Mexico City, Dif, Mexico

Puebla, , Mexico

Maastricht, Limburg, Netherlands

Amsterdam, Noord Holland, Netherlands

Jeddah, Makkah Al Mukarramah, Saudi Arabia

Valencia, València, Spain

Taipei City, Taipei, Taiwan

Ploiești, , Romania

Pontevedra, Pontevedra [Pontevedra], Spain

Patients applied

0 patients applied

Timeline

First submit

Trial launched

Trial updated

Estimated completion

Not reported