8O - First-line (1L) datopotamab deruxtecan (Dato-DXd) + durvalumab ± carboplatin in advanced or metastatic non-small cell lung cancer (a/mNSCLC): Results from TROPION-Lung04 (cohorts 2 and 4)

Background

Dato-DXd, a novel TROP2-directed antibody-drug conjugate, has shown promising efficacy in patients with mNSCLC as monotherapy or when combined with PD-(L)1 inhibitors.

Methods

TROPION-Lung04 (NCT04612751), a phase 1b, open-label, dose-escalation and expansion study, enrolled patients with confirmed a/mNSCLC without actionable genomic alterations. Patients were treatment-naïve or had received 1 prior line of chemotherapy for a/mNSCLC. Cohort 2 (C2) and cohort 4 (C4) received Dato-DXd (6 mg/kg) + durvalumab (1120 mg) Q3W; C4 also received carboplatin (4 cycles, AUC5) Q3W. All patients received treatment until disease progression or unacceptable toxicity. Primary endpoint was safety. Secondary endpoints included objective response rate (ORR) and duration of response (DoR) per investigator (RECIST v1.1). We report updated analyses of patients who received 1L treatment in C2 and C4.

Results

At data cut-off (DCO; 23 May, 2024), 52 patients received 1L treatment with Dato-DXd + durvalumab ± carboplatin (C2, N=15; C4, N=37); of which 73.3% (C2) and 48.6% (C4) had non-squamous histology. In C2 and C4, median treatment duration was 6.9 (range 0.7–26.9) and 6.2 months (range 0.7–25.8); 2 (13.3%) and 13 (35.1%) patients were still on treatment at DCO. All patients (100%) had treatment-emergent adverse events (TEAEs); 65.4% had grade ≥3 TEAEs. Most common TEAEs were stomatitis (61.5%) and nausea (48.1%). Ocular surface events occurred in 16 patients (grade ≥3, n=1). Adjudicated drug-related interstitial lung disease/pneumonitis was reported in 7 patients (grade 4, n=1; grade 5, n=1). Confirmed ORR was 53.3% and 56.8% for C2 and C4, respectively. Responses were observed across all evaluated PD-L1 levels and in both squamous and non-squamous histologies. Median DoR was 15.0 months (95% CI 4.5, NE) for C2 and 8.8 months (95% CI 4.6, NE) for C4.

Conclusions

With longer follow-up, Dato-DXd + durvalumab ± carboplatin had encouraging activity as 1L treatment for a/mNSCLC. The safety profile of Dato-DXd was comparable to previously reported data.

Clinical trial identification

NCT04612751.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Mark Holland of Ashfield MedComms (Macclesfield, UK), an Inizio company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca PLC in collaboration with Daiichi Sankyo.

Funding

AstraZeneca PLC in collaboration with Daiichi Sankyo.

Disclosure

K. Cuppens: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Hoffmann-La Roche, Iteos Therapeutics, Janssen, Merck Sharp & Dohme, Pfizer, Pierre-Fabre Oncology; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Hoffmann-La Roche, Janssen, Merck Sharp & Dohme; Financial Interests, Personal, Expert Testimony: AstraZeneca, Merck Sharp & Dohme. K. Papadopoulos: Financial Interests, Personal, Advisory Role: Basilea, Bicycle Therapeutics, Turning Point Therapeutics; Financial Interests, Institutional, Funding: 3D Medicines, AbbVie, Amgen, Anheart Therapeutics, AstraZeneca, Bayer, Bicycle Therapeutics, BioNTech, CytomX Therapeutics, Daiichi Sankyo, Debiopharm Group, F-star, Incyte, Jounce Therapeutics, Kezar Life Sciences, Lilly, MabSpace Biosciences, Merck, Mirati Therapeutics, Monte Rosa Therapeutics, Pfizer, PharmaMar, Regeneron, Revolution Medicines, Sensei Biotherapeutics, Storm Therapeutics, Syros Pharmaceuticals, Tempest Therapeutics, Treadwell Therapeutics. M. Nishio: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb Japan, Chugai Pharma, Daiichi Sankyo/UCB Japan, Eisai, Janssen, Lilly, Merck, MSD, Nippon Kayaku, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takeda; Financial Interests, Institutional, Funding: Amgen, AstraZeneca, Bristol Myers Squibb, Janssen, Lilly, Merck, MSD, Pfizer, Taiho Pharmaceutical, Takeda. K. Wakuda: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Boehringer Ingelheim, Novartis, Ono Pharmaceutical, Taiho Pharmaceutical. M. Gutierrez: Financial Interests, Personal, Stocks/Shares: Cota Healthcare; Financial Interests, Personal, Advisory Role: Celularity, Guardant Health, and Sanofi; Financial Interests, Personal, Invited Speaker: BMS and Merck; Financial Interests, Institutional, Funding: Acerta Pharma, Adlai Nortye, Arcus Biosciences, Array BioPharma, Bayer, Bellicum Pharmaceuticals, BMS, Boehringer Ingelheim, Celgene, Checkpoint Therapeutics, Compass Therapeutics, Constellation Pharmaceuticals, Cullinan Oncology, Cyteir, Daiichi Sankyo, Eisai, EMD Serono, EMD Serono, Erasca, Inc, Fate Therapeutics, Georgetown Univ, GSK, GSB Pharma, Hackensack Meridian Health, Imugene, Incyte, Infinity Pharmaceuticals, ITeos Therapeutics, Janssen, Johnson & Johnson, KSQ Therapeutics, MedImmune, Memorial Sloan-Kettering Cancer Center, Merck, Millennium, Mirati Therapeutics, Moderna Therapeutics, NextCure, Nimbus Therapeutics, Pfizer, Pharmacyclics, Rapa Therapeutics, Regeneron, Roche/Genentech, Sanofi, Seagen, Silenseed, Synlogic, Tesaro, Turning Point Therapeutics, Vedanta Biosciences, VelosBio, Verastem, Vincerx Pharma. S. Murakami: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharma, Takeda, Eli Lilly, MSD, Pfizer, Novartis and Taiho Pharmaceutical; Financial Interests, Institutional, Funding: AstraZeneca, Takeda, Chugai Pharma, Sanofi, MSD, Daiichi Sankyo, Ono Pharmaceutical and Janssen Pharma. C. Chiu: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Eli Lilly, Merck KGaA, Merck Sharp & Dohme, Merck, Novartis, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Roche, Takeda. E. Kalinka: Financial Interests, Personal, Advisory Role: MSD, BMS; Financial Interests, Personal, Invited Speaker: MSD, BMS, AstraZeneca, Roche, Gilead, Pfizer, Medison, Eli Lilly; Financial Interests, Personal, Principal Investigator: MSD, BMS, AstraZeneca, Roche, Gilead, Pfizer, Regeneron, Eli Lilly, AbbVie, Celcuity, Daiichi Sankyo. A. Spira: Financial Interests, Personal, Stocks/Shares: Lilly; Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca/MedImmune, Bayer, Bristol Myers Squibb, CytomX Therapeutics, Janssen Oncology, Merck, Novartis, Takeda; Financial Interests, Personal, Invited Speaker: Amgen, Black Diamond Therapeutics, Daiichi Sankyo/AstraZeneca, Gritstone Bio, Incyte, Janssen Research & Development, Jazz Pharmaceuticals, Lilly, Mersana, Mirati Therapeutics, Novartis, Regeneron, Sanofi, Takeda; Financial Interests, Institutional, Invited Speaker: Array BioPharma, AstraZeneca/MedImmune, Blueprint Medicines, Bristol Myers Squibb, Merck; Financial Interests, Institutional, Funding: AbbVie, ADC Therapeutics, ADC Therapeutics, Alkermes, Amgen, Arch Therapeutics, ArriVent Biopharma, Astellas Pharma, Astex Pharmaceuticals, AstraZeneca, Black Diamond Therapeutics, Blueprint Medicines, BluPrint Oncology, Boehringer Ingelheim, Bristol Myers Squibb, CytomX Therapeutics, Daiichi Sankyo, Gritstone Bio, Ignyta, Incyte, Janssen Oncology, LAM Therapeutics, Loxo, Macrogenics, Medikine, MedImmune, Mersana, Mirati Therapeutics, Nalo therapeutics, Novartis, Plexxikon, Regeneron, Revolution Medicines, Roche, Rubius Therapeutics, Scorpion Therapeutics, Synthekine, Takeda. V. Haddad: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Hinzmann, X. Shi: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. S.N. Waqar: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Boehringer Ingelheim, Janssen, Daiichi Sankyo and Gilead; Financial Interests, Institutional, Funding, to support and oversee the Lung-MAP master protocol and sub study activities: SWOG-Clinical Trials Partnership; Financial Interests, Personal, Principal Investigator: AbbVie, Gilead, Immunomedics, Inc., Daiichi Sankyo, Cullinan Pearl, Verastem Inc, Janssen Research & Development, LLC, Elevation Oncology, Genentech, Verastem, Advenchen, Ribon, Loxo Oncology, Takeda, Hoffman-LaRoche, Nuvalent. All other authors have declared no conflicts of interest.