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 May 09, 2025
Recruiting
Keywords
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.
Contacts
Jennifer Cobb
Immunology at National Institute of Allergy and Infectious Diseases (NIAID)
Locations
Frankston, Victoria, Australia
Elizabeth Vale, South Australia, Australia
Joondalup, Western Australia, Australia
Tainan City, Tainan, Taiwan
Liège, , Belgium
London, London, City Of, United Kingdom
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
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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
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Ahmedabad, Gujarat, India
Ahmedabad, Gujarat, India
Thiruvananthapuram, Kerala, India
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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
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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
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Kraków, Małopolskie, Poland
Prabuty, Pomorskie, Poland
Poznan, Wielkopolskie, Poland
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Katowice, , Poland
Lisbon, Lisboa, Portugal
Coimbra, , Portugal
Porto, , Portugal
Bucharest, București, Romania
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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
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Barcelona, Barcelona [Barcelona], Spain
Hospitalet, Barcelona [Barcelona], Spain
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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
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Tamarac, Florida, United States
Tampa, Florida, United States
Fort Eisenhower, Georgia, United States
Marietta, Georgia, United States
Arlington Heights, Illinois, United States
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York, Pennsylvania, United States
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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
Recoleta, Región Metropolitana De Santiago, Chile
Patients applied
Timeline
First submit
Trial launched
Trial updated
Estimated completion
Not reported