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NCT07098338PHASE2Recruiting

A Study of Novel Combinations in Non-Small Cell Lung Cancer (NSCLC)

AstraZeneca

Start Date

8/7/2025

Completion Date

4/6/2029

Summary

This is a Phase II, multi-center, open-label platform study evaluating novel combination treatment options in participants with locally advanced or metastatic NSCLC. The study will consist of several sub-studies, each evaluating the safety, tolerability, and preliminary antitumour activity of various treatment combinations. This study will be conducted in approximately 80 centers globally across 10 countries.

Detailed Description

The master protocol will include 3 sub-studies, each focused on a specific disease population. * Sub-study 1 will investigate rilvegostomig± ramucirumab in 1L non-actionable genomic alterations (AGA) NSCLC with PD-L1 ≥50%. * Sub-study 2 will investigate rilvegostomig + ramucirumab in 1L non-actionable genomic alterations (AGA) NSCLC with PD-L1 1-49%. * Sub-study 3 will investigate Dato-DXd + ramucirumab ± rilvegostomig in 2/3L AGA+ Each sub-study may include 2 parts (unless stated in the individual sub study protocols): Part A: one or more Safety Run-in cohort(s), and Part B: one or more Dose Expansion cohort(s).

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria for All Sub-studies: * Participant must be ≥ 18 years of age at the time of signing the ICF * WHO/ECOG performance status of 0 or 1 * At least 1 lesion that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline. * Adequate bone marrow and organ function * Life expectancy ≥ 12 weeks * Provision of acceptable tumour tissue Specific Inclusion Criteria for Sub-Study 1 and Sub-Study 2: * Histologically or cytologically documented advanced or metastatic NSCLC * PD-L1 TC ≥ 1% (TC≥ 50% for sub-study 1, 1-49% for sub-study 2) * Absence of sensitizing EGFR mutations or ALK rearrangements. No known other Actionable Genomic Alterations(AGAs) Specific Inclusion Criteria for Sub-Study 3: * Histologically or cytologically documented advanced or metastatic non-squamous NSCLC * Documented positive AGA and had progressed on prior targeted therapy Exclusion Criteria for All Sub-studies: * As judged by the investigator, any severe or uncontrolled systemic diseases, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol * Active or prior documented autoimmune or inflammatory disorders * Persistent toxicities (CTCAE Grade ≥ 2) (NCI CTCAE v5.0) caused by previous anti cancer therapy, excluding alopecia. * Spinal cord compression or leptomeningeal carcinomatosis for sub-study 1 and sub-study 2. Unstable spinal cord compression for sub-study 3 * Unstable brain metastases * History of another primary malignancy. * Active infection, including TB and infections with HIV, HBV (verified by known positive HBsAg result), HCV. * Uncontrolled or significant cardiac disease * Receipt of prior systemic chemotherapy/chemoradiation/immunotherapy for advanced NSCLC for sub-study 1 and sub-study 2. * Prior exposure to immune-mediated therapy * History of uncontrolled hypertension, and active bleeding diseases, and high risks of bleeding and disorders of coagulation * Any concurrent anti-cancer treatment. * Receipt of live, attenuated vaccine within 30 days prior to the first dose of study intervention.

Interventions

DRUG

Rilvegostomig

DRUG

Ramucirumab

DRUG

Dato-DXd

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Conditions

Non-Small Cell Lung Cancer

Locations

Research Site

Santa Monica, California 90404

United States

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Santa Rosa, California 95403

United States

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Atlanta, Georgia 30318

United States

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Baltimore, Maryland 21231

United States

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Houston, Texas 77090

United States

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Fairfax, Virginia 22031

United States

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Heidelberg, 3084

Australia

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Nedlands, 6009

Australia

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Woodville, 5011

Australia

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Toronto, Ontario M5G 2M9

Canada

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Changsha, 410013

China

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Chengdu, 610041

China

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Deyang, 618000

China

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Dongguan, 523059

China

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Fuzhou, 350014

China

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Guangzhou, 510080

China

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Guangzhou, 510100

China

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Hangzhou, 310014

China

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Hefei, 230022

China

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Linyi, 276001

China

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Mianyang, 621000

China

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Nanchang, 330000

China

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Nanchang, 330006

China

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Shantou,

China

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Shenyang, 110042

China

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Wuhan, 430022

China

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Zhengzhou, 450000

China

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Zhengzhou, 450008

China

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Zhuhai, 519000

China

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Avignon, 84902

France

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Paris, 75005

France

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Rennes, 35000

France

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Saint-Herblain, 44805

France

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Suresnes, 92150

France

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Aviano, 33081

Italy

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Catania, 95123

Italy

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Meldola, 47014

Italy

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Milan, 20141

Italy

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Milan, 35128

Italy

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Orbassano, 10043

Italy

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Roma, 00144

Italy

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Rozzano, 20089

Italy

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Bunkyō City, 113-8677

Japan

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Fukuyama-shi, 722-0001

Japan

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Kobe, 650-0047

Japan

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Kurume-shi, 830-0011

Japan

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Kyoto, 602-8566

Japan

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Kyoto, 606-8507

Japan

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Osaka, 541-8567

Japan

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Sakaishi, 591-8555

Japan

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Shinjuku-ku, 162-8655

Japan

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Wakayama, 641-8510

Japan

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Yokohama, 236-0051

Japan

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Singapore, 119082

Singapore

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Singapore, 168583

Singapore

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Cheongju-si, 28644

South Korea

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Namdong-gu, 21565

South Korea

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Seongnam-si, 13496

South Korea

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Seoul, 03080

South Korea

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Seoul, 06351

South Korea

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Seoul, 3722

South Korea

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Seoul, 5505

South Korea

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Suwon, 16247

South Korea

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Suwon, 16499

South Korea

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A Coruña, 15006

Spain

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Madrid, 28041

Spain

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Manresa, 08243

Spain

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Málaga, 29009

Spain

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Santander, 39008

Spain

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Valencia, 46010

Spain

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Liuying, 736

Taiwan

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Taichung, 402

Taiwan

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Taichung, 40447

Taiwan

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Tainan, 70403

Taiwan

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Tainan, 710

Taiwan

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Taipei, 100

Taiwan

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Taipei, 110

Taiwan

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Taipei, 11217

Taiwan

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Taoyuan, 00333

Taiwan

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Bangkok, 10330

Thailand

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Bangkok, 10400

Thailand

Research Site

Bangkok, 10700

Thailand

Research Site

Banphaeo, 74120

Thailand