ENHERTU® (fam-trastuzumab deruxtecan-nxki) demonstrated robust and durable tumor response of 54.9% in patients with HER2-mutant metastatic non-small cell lung cancer

Rhea-AI Summary

ENHERTU (fam-trastuzumab deruxtecan-nxki) has shown a significant tumor response in previously treated patients with HER2-mutant unresectable and/or metastatic non-squamous non-small cell lung cancer (NSCLC), as demonstrated in the Phase II DESTINY-Lung01 trial. The results revealed a confirmed objective response rate (ORR) of 54.9% and a disease control rate (DCR) of 92.3%. The median overall survival was 17.8 months, highlighting ENHERTU’s potential as a new standard of care for this patient population. The overall safety profile aligns with prior studies, with manageable adverse events.

Positive

• Confirmed objective response rate (ORR) of 54.9% in HER2-mutant NSCLC.
• Disease control rate (DCR) of 92.3%.
• Median overall survival (OS) of 17.8 months.
• ENHERTU is the first HER2-directed therapy showing significant tumor response in this population.

Negative

• Adverse events include neutropenia (18.7%) and anemia (9.9%).
• Fatalities due to treatment-related interstitial lung disease (ILD) or pneumonitis reported.

First HER2-directed therapy to show a strong tumor response in this population

Data from HER2-mutant cohort of pivotal DESTINY-Lung01 Phase II trial presented at ESMO and published in The New England Journal of Medicine

WILMINGTON, Del.--(BUSINESS WIRE)-- Detailed primary results from the positive Phase II DESTINY-Lung01 trial of ENHERTU^® (fam-trastuzumab deruxtecan-nxki), the AstraZeneca and Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) HER2-directed antibody drug conjugate (ADC), showed a robust and durable tumor response in previously treated patients with HER2-mutant (HER2m) unresectable and/or metastatic non-squamous non-small cell lung cancer (NSCLC). Results presented during a late-breaking Proffered Paper session at the European Society for Medical Oncology (ESMO) Congress 2021 and simultaneously published in The New England Journal of Medicine confirm ENHERTU as the first HER2-directed therapy to show a strong tumor response in this patient population.

Lung cancer is the leading cause of cancer death among both men and women, and accounts for about one-fifth of all cancer deaths globally, with 80-85% classified as NSCLC.^1-3 There are currently no medicines approved specifically for the treatment of HER2m NSCLC, which affects approximately 2-4% of patients with NSCLC.^4,5

Primary results from the HER2m cohort (cohort 2) of DESTINY-Lung01 in previously treated HER2m NSCLC demonstrated a confirmed objective response rate (ORR) of 54.9% in patients treated with ENHERTU (6.4 mg/kg) as assessed by independent central review (ICR). One (1.1%) complete response (CR) and 49 (53.8%) partial responses (PR) were observed. A confirmed disease control rate (DCR) of 92.3% was seen with a reduction in tumor size observed in most patients. After a median follow-up of 13.1 months, the median duration of response (DoR) for ENHERTU was 9.3 months. The median progression-free survival (PFS) was 8.2 months and the median overall survival (OS) was 17.8 months.

Bob Li, MD, PhD, MPH, Memorial Sloan Kettering Cancer Center, said: “Despite more than 20 years of research into HER2-mutations in non-small cell lung cancer, there are currently no approved HER2-targeted therapies for non-small cell lung cancer. Patients with HER2-mutant non-small cell lung cancer are associated with younger age, female sex, never smoking history and a poor prognosis with increased incidence of brain metastases, representing unmet clinical need. The impressive results from DESTINY-Lung01 showed most patients experienced a reduction in tumor size with ENHERTU treatment, suggesting this medicine has the potential to become the new standard of care for these patients.”

Susan Galbraith, Executive Vice President, Oncology R&D, said: “Lung cancer is a devastating diagnosis, and for patients with HER2-mutant lung cancer, a targeted treatment for their specific disease has not been an option. These data reinforce the potential of ENHERTU to become the first HER2-directed therapy for these patients and reaffirm how this treatment is truly delivering on its transformative potential.”

Ken Takeshita, Global Head, Research and Development, Daiichi Sankyo, said: “ENHERTU is the first HER2-directed therapy to demonstrate a robust and durable tumor response in patients with HER2-mutant non-small cell lung cancer. This is potentially great news for patients, and so we are continuing to conduct research, with the goal of bringing ENHERTU to those with this specific form of lung cancer.”

Responses were observed across HER2m subtypes, as well as in patients with no detectable HER2 expression or HER2 gene amplification. Efficacy was observed in subgroups including prior treatment with platinum-based therapy, or platinum-based and anti–PD-(L)1 therapy, as well as asymptomatic brain metastases at baseline.

Summary of results

Efficacy Measure	HER2m Total Evaluable (n=91)i
Confirmed ORR (%) (95% CI)ii,iii	54.9% (44.2 – 65.4)
Complete response (%)	1.1%
Partial response (%)	53.8%
Stable disease (%)	37.4%
DCR (95% CI)iv	92.3% (84.8–96.9)
Median DoR (months) (95% CI)	9.3 months (5.7 – 14.7)
Median PFS (months) (95% CI)	8.2 months (6.0 – 11.9)
Median OS (months) (95% CI)	17.8 months (13.8 – 22.1)
i ENHERTU 6.4mg/kg; median duration of follow-up was 13.1 months ii As assessed by independent central review iii ORR is (CR + PR) iv DCR is (CR + PR +SD)

The overall safety profile of ENHERTU was consistent with previous ENHERTU NSCLC trials, with no new safety signals identified. The most common Grade 3 or higher drug-related treatment-emergent adverse events were neutropenia (18.7%) and anemia (9.9%). Rates of treatment-related interstitial lung disease (ILD) or pneumonitis were consistent with previous trials in lung cancer. There were 24 cases of ILD or pneumonitis, as determined by an independent adjudication committee with the majority (75%) low Grade (Grade 1 or 2), with four Grade 3 and two Grade 5 (ILD or pneumonitis-related death).

In May 2020, ENHERTU was granted Breakthrough Therapy Designation in the US for the treatment of HER2m metastatic NSCLC.

ENHERTU is being further assessed in a comprehensive clinical development program evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.

Several presentations featured during the ESMO Congress 2021 will showcase the strength and depth of ENHERTU data across multiple tumor types, including gastric, lung and breast cancers, reinforcing the transformational potential of this medicine in the treatment of HER2-targetable cancers.

Important Safety Information

Indications

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

• Unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.
  
  This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY   Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms. Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

Contraindications

None.

Warnings and Precautions

Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.

Metastatic Breast Cancer

In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with ENHERTU. Median time to first onset was 4.1 months (range: 1.2 to 8.3).

Locally Advanced or Metastatic Gastric Cancer

In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21.0).

Neutropenia

Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 10⁹/L) interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 10⁹/L) interrupt ENHERTU until resolved to Grade 2 or less. Reduce dose by one level. For febrile neutropenia (ANC <1.0 x 10⁹/L and temperature >38.3ºC or a sustained temperature of ≥38ºC for more than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one level.

Metastatic Breast Cancer

In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU 5.4mg/kg, a decrease in neutrophil count was reported in 62% of patients. Sixteen percent had Grade 3 or 4 decrease in neutrophil count. Median time to first onset of decreased neutrophil count was 23 days (range: 6 to 547). Febrile neutropenia was reported in 1.7% of patients.

Locally Advanced or Metastatic Gastric Cancer

In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.

Left Ventricular Dysfunction

Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (0.9%) of asymptomatic LVEF decrease were reported. In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure.

Embryo-Fetal Toxicity

ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU.

Additional Dose Modifications

Thrombocytopenia

For Grade 3 thrombocytopenia (platelets <50 to 25 x 10⁹/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 10⁹/L) interrupt ENHERTU until resolved to Grade 1 or less. Reduce dose by one level.

Adverse Reactions

Metastatic Breast Cancer

The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).

Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.

ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (79%), white blood cell count decreased (70%), hemoglobin decreased (70%), neutrophil count decreased (62%), fatigue (59%), vomiting (47%), alopecia (46%), aspartate aminotransferase increased (41%), alanine aminotransferase increased (38%), platelet count decreased (37%), constipation (35%), decreased appetite (32%), anemia (31%), diarrhea (29%), hypokalemia (26%), and cough (20%).

Locally Advanced or Metastatic Gastric Cancer

The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma in DESTINY‑Gastric01. Patients intravenously received at least one dose of either ENHERTU (N=125) 6.4 mg/kg once every three weeks or either irinotecan (N=55) 150 mg/m² biweekly or paclitaxel (N=7) 80 mg/m² weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) in the ENHERTU group and 2.8 months (range: 0.5 to 13.1) in the irinotecan/paclitaxel group.

Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in one patient each (0.8%).

ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and hypokalemia. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (75%), white blood cell count decreased (74%), neutrophil count decreased (72%), lymphocyte count decreased (70%), platelet count decreased (68%), nausea (63%), decreased appetite (60%), anemia (58%), aspartate aminotransferase increased (58%), fatigue (55%), blood alkaline phosphatase increased (54%), alanine aminotransferase increased (47%), diarrhea (32%), hypokalemia (30%), vomiting (26%), constipation (24%), blood bilirubin increased (24%), pyrexia (24%), and alopecia (22%).

Use in Specific Populations

• Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months following the last dose of ENHERTU.
• Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
• Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
• Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
• Geriatric Use: Of the 234 patients with HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, 26% were ≥65 years and 5% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (53%) as compared to younger patients (42%). Of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients.
• Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor.

To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

HER2-mutant NSCLC

Lung cancer is the leading cause of cancer death among both men and women and accounts for about one-fifth of all cancer deaths globally, with 80-85% classified as NSCLC.^1-3 For patients with metastatic disease, prognosis is particularly poor, as only approximately 6% will live beyond five years after diagnosis.²

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including lung, breast, gastric and colorectal cancers. HER2 gene alterations (called HER2 mutations) have been identified in NSCLC, specifically adenocarcinomas, as distinct molecular targets and have been reported in approximately 2-4% of patients with NSCLC.^4,5 These HER2 gene mutations are predominantly seen in younger women, with no smoking history and have been independently associated with cancer cell growth and poor prognosis with an increased incidence of brain metastases.^4,6-10 Although the role of anti-HER2 treatment is well established in breast and gastric cancer, HER2 is still an emerging biomarker in NSCLC with no approved HER2-directed therapies.^4,11

DESTINY-Lung01

DESTINY-Lung01 is a global, Phase II, open-label, multi-center, two-cohort trial testing the safety and efficacy of ENHERTU in patients with HER2-mutant (6.4 mg/kg) or HER2 overexpressing (defined as IHC3+ or IHC2+) unresectable and/or metastatic non-squamous NSCLC. Patients had progressed after one or more systemic therapies including chemotherapy, molecular targeted therapy or immunotherapy. The primary endpoint is confirmed ORR by independent central review. ORR, or tumor response rate, represents the percentage of patients whose disease decreased and/or disappears. Key secondary endpoints include DoR, DCR, PFS and OS.

DESTINY-Lung01 enrolled approximately 180 patients at multiple sites including the US, Europe and Japan. For more information about the trial, visit ClinicalTrials.gov.

ENHERTU

ENHERTU (fam-trastuzumab deruxtecan-nxki) is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

ENHERTU (5.4mg/kg) is approved in Canada, the EU, Israel, Japan, the UK and the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the results from the DESTINY-Breast01 trial.

ENHERTU (6.4mg/kg) is also approved in Israel, Japan and the US for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

ENHERTU development program

A comprehensive development program is underway globally, evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

ENHERTU was highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the “ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers,” based on data from both the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of the targeted therapy advances of the year in non-small cell lung cancer (NSCLC), based on the interim results of the HER2-mutated cohort of the DESTINY-Lung01 trial.

In May 2020, ENHERTU also received Breakthrough Therapy Designation for the treatment of patients with metastatic NSCLC whose tumors have a HER2-mutation and with disease progression on or after platinum-based therapy.

Daiichi Sankyo collaboration

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of ENHERTU and datopotamab deruxtecan.

AstraZeneca in lung cancer

AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including osimertinib and gefitinib; durvalumab and tremelimumab; ENHERTU and datopotamab deruxtecan in collaboration with Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

AstraZeneca in oncology

AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

References

1. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Accessed August 2021.
2. ASCO. Cancer.net. Lung Cancer – Non-small Cell. Accessed August 2021.
3. Cheema, PK et al. Perspectives on treatment advances for stage III locally advanced unresectable non-small-cell lung cancer. Curr Oncol. 2019;26(1):37-42.
4. Liu, S et al. Targeting HER2 Aberrations in Non-Small Cell Lung Cancer with Osimertinib. Clin Cancer Research. 2018;24(11):2594-2604.
5. Campbell, JD et al. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nature Genetics. 2016;48(6):607-16.
6. Stephens P, et al. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 2004;431:525-6.
7. Mazières J, et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol 2013;31:1997-2003.
8. Arcila ME, et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res 2012;18:4910-8.
9. Pillai RN, et al. HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium. Cancer 2017;123:4099-105.
10. Offin M, et al. Frequency and outcomes of brain metastases in patients with HER2-mutant lung cancers. Cancer 2019;125:4380-7.
11. Zhou, J et al. Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versus HER2-directed therapies. Ther Adv Med Oncol. 2020;12.

Dr. Li has provided uncompensated advisory services to AstraZeneca and Daiichi Sankyo.

US-57311 Last Updated 9/21

View source version on businesswire.com: https://www.businesswire.com/news/home/20210918005008/en/

Media Inquiries

Holly Campbell +1 302 885 2677

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Source: AstraZeneca

FAQ

What are the results of the DESTINY-Lung01 trial for AZN?

The DESTINY-Lung01 trial showed a confirmed objective response rate (ORR) of 54.9% and a disease control rate (DCR) of 92.3% for AZN's ENHERTU in HER2-mutant NSCLC.

How does ENHERTU perform in HER2-mutant lung cancer according to the latest trial data?

ENHERTU displayed a median overall survival of 17.8 months and a median duration of response of 9.3 months in HER2-mutant lung cancer patients.

What safety concerns are associated with ENHERTU as reported in the press release?

The safety profile includes adverse events such as neutropenia (18.7%) and anemia (9.9%), with some cases of treatment-related ILD and pneumonitis.

When were the results from the DESTINY-Lung01 trial presented?

The results were presented at the European Society for Medical Oncology (ESMO) Congress 2021.