ENHERTU® (fam-trastuzumab deruxtecan-nxki) data will show the potential to improve survival for metastatic breast cancer patients and define a new segment of HER2-low disease
Results from multiple trials further reinforce strength of industry-leading portfolio and pipeline, including novel combinations, across cancers with high unmet need
WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca advances its ambition to redefine cancer care with new data to be presented across its diverse and industry-leading portfolio of cancer medicines at the American Society of Clinical Oncology (ASCO) Annual Meeting, June 3-7, 2022.
A total of 18 approved and potential new medicines from AstraZeneca will be featured across more than 100 abstracts, including nine oral presentations and a plenary presentation of the DESTINY-Breast04 Phase III trial for ENHERTU® (fam-trastuzumab deruxtecan-nxki) in HER2-low metastatic breast cancer.
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Our five leading Oncology medicines have each set new standards for patient outcomes across many cancers. Our data at ASCO will showcase our continued investment in driving innovation with these medicines as well as their long-term impact in real-world settings. In particular, the groundbreaking data from DESTINY-Breast04 will show the potential of ENHERTU to treat patients with HER2-low metastatic breast cancer who have never before been eligible for HER2-targeted treatments.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “At AstraZeneca, we are pioneering new biomarkers and novel therapeutic modalities in our ambition to attack cancer from every angle and deliver personalized medicines to more patients. The results from DESTINY-Breast04 support the potential for ENHERTU to redefine the classification and treatment of breast cancer across the spectrum of HER2 expression. We are also excited to share promising clinical data for our bispecific PD1-CTLA4 antibody MEDI5752 in advanced renal cell carcinoma, designed to have both of these clinically validated checkpoint targets in one molecule, delivering efficacy with an improved tolerability profile.”
Leading through disruption in breast cancer
A late-breaking plenary presentation will highlight the potentially practice-changing results of the DESTINY-Breast04 trial of ENHERTU in patients with HER2-low metastatic breast cancer. DESTINY-Breast04 is the first-ever Phase III trial of a HER2-directed therapy to show statistically significant and clinically meaningful benefit in both progression-free survival (PFS) and overall survival (OS) in patients with HER2-low unresectable and/or metastatic breast cancer regardless of hormone receptor status compared to standard-of-care chemotherapy.
Additionally, data from a retrospective study will estimate the prevalence of HER2-low breast cancer and describe its clinical and pathological characteristics, to help identify patients with HER2-low expressing tumors who may benefit from HER2-targeted therapy.
Further results will be shared from dose-finding and dose-expansion studies of ENHERTU in combination with other anti-cancer agents in patients with advanced or metastatic HER2-positive breast cancer (DESTINY-Breast07) and HER2-low breast cancer (DESTINY-Breast08).
Data will also be presented from a safety follow-up of the DESTINY-Breast03 Phase III trial of ENHERTU in the treatment of patients with unresectable or metastatic HER2-positive breast cancer previously treated with trastuzumab and a taxane. ENHERTU was recently approved in the US for patients in this setting.
Revealing the full potential of an industry-leading portfolio and pipeline
Beyond breast cancer, AstraZeneca will share results from multiple trials highlighting its focus on delivering life-changing cancer medicines for patients with high unmet need. Data will also support the Company’s commitment to realizing the full potential of its leading medicines with ongoing analyses, real-world data and research into novel combinations.
- MEDI5752 – An oral presentation will share safety and clinical activity results for MEDI5752 in patients with advanced renal cell carcinoma as a monotherapy treatment. MEDI5752 is a novel bispecific antibody that simultaneously targets the immune checkpoint proteins PD-1 and CTLA-4.
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CALQUENCE® (acalabrutinib) – Updated data from the ELEVATE-TN and ASCEND Phase III trials will highlight long-term safety and efficacy results of CALQUENCE in patients with chronic lymphocytic leukemia (CLL) regardless of line of therapy.
Presentations include updated data with approximately five-years of median follow-up from the ELEVATE-TN trial, which has demonstrated sustained clinical benefit of CALQUENCE either in combination with obinutuzumab or as monotherapy compared to obinutuzumab plus chlorambucil, providing flexibility to tailor treatment for adults with treatment-naïve CLL.
Additionally, updated results from the ASCEND Phase III trial with approximately four years of median follow-up will highlight the sustained reduction of disease progression or death for CALQUENCE compared to idelalisib plus rituximab or bendamustine plus rituximab in patients with relapsed or refractory CLL, as well as a maintained safety profile.
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IMFINZI® (durvalumab) – Patient-reported outcomes from the HIMALAYA trial will highlight quality of life for patients treated with a single priming dose of tremelimumab added to IMFINZI in 1st-line unresectable liver cancer (STRIDE regimen). HIMALAYA is the first Phase III trial to show that a dual immunotherapy regimen has improved OS versus sorafenib in this setting. Tremelimumab with IMFINZI was recently accepted under Priority Review in the US by the Food and Drug Administration (FDA) based on this trial.
Patient-reported outcomes will also be presented from the TOPAZ-1 trial of IMFINZI plus standard-of-care chemotherapy (gemcitabine plus cisplatin) in 1st-line advanced biliary tract cancer. TOPAZ-1 is the first Phase III trial to show improved survival with an immunotherapy combination versus chemotherapy alone in this setting.
An additional regional subgroup analysis for the TOPAZ-1 trial will compare efficacy outcomes, including OS, for Asian patients with other geographies. IMFINZI plus chemotherapy was recently granted Priority Review in the US by the FDA based on this trial.
Further clinically relevant safety data from the positive POSEIDON Phase III trial of IMFINZI, tremelimumab and chemotherapy in 1st-line metastatic non-small cell lung cancer (NSCLC) will also be presented.
- LYNPARZA® (olaparib) – Data from the PROpel Phase III trial will further reinforce the safety profile of LYNPARZA plus abiraterone in the treatment of 1st-line metastatic castration-resistant prostate cancer (mCRPC). These data build on PROpel efficacy data, which demonstrated that this combination significantly delayed disease progression versus standard-of-care abiraterone in 1st-line mCRPC in patients with or without homologous recombination repair gene mutations. LYNPARZA is the first PARP inhibitor to demonstrate clinical benefit in combination with a new hormonal agent versus abiraterone alone in this setting.
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TAGRISSO® (osimertinib) – Results will be shared from the externally sponsored OPAL Phase II trial in previously untreated EGFR-mutated (EGFRm) NSCLC that evaluated whether the addition of platinum-based chemotherapy to TAGRISSO can improve patient outcomes. This combination is also being tested in the ongoing FLAURA2 Phase III trial.
Real-world data will also be presented to better inform unmet needs and treatment strategies among patients with resectable early-stage NSCLC, providing valuable insights into EGFRm disease prevalence and rates of recurrence, despite adjuvant chemotherapy, in this population. TAGRISSO is approved for the adjuvant treatment of early-stage (IB, II and IIIA) EGFRm NSCLC based on the ADAURA Phase III trial.
Collaboration in the scientific community is critical to improving outcomes for patients. AstraZeneca is collaborating with, Daiichi Sankyo Company Limited to develop and commercialize ENHERTU and Merck & Co., Inc., Kenilworth, NJ, US (known as MSD outside the US and Canada) to develop and commercialize LYNPARZA.
Key AstraZeneca presentations during ASCO 2022
Lead author |
Abstract title |
Presentation details |
Antibody drug conjugates |
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Modi, S |
Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Results of DESTINY-Breast04, a randomized, phase 3 study. |
Abstract #LBA3 Plenary Session June 5, 2022 2:17pm (CDT)
|
Hamilton, EP |
Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients (pts) with HER2-positive (HER2+) unresectable and/or metastatic breast cancer (mBC): Safety follow-up of the randomized, phase 3 study DESTINY-Breast03. |
Abstract #1000 Oral Abstract Session Breast Cancer—Metastatic June 4, 2022 1:15pm (CDT) |
Andre, F |
Dose-finding and -expansion studies of trastuzumab deruxtecan in combination with other anti-cancer agents in patients (pts) with advanced/metastatic HER2+ (DESTINY-Breast07 [DB-07]) and HER2-low (DESTINY-Breast08 [DB-08]) breast cancer (BC). |
Abstract #3025 Poster Session Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology June 5, 2022 8:00am (CDT) |
Immuno-Oncology |
|
|
Cho, BC |
Durvalumab (D) +/- tremelimumab (T) + chemotherapy (CT) in first-line (1L) metastatic (m) NSCLC: AE management in POSEIDON. |
Abstract #9035 Poster Session Lung Cancer—Non-Small Cell Metastatic June 6, 2022 8:00am (CDT) |
Sangro, B |
Patient-reported outcomes from the phase 3 HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. |
Abstract #4074 Poster Session Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary June 4, 2022 8:00am (CDT) |
Burris III, HA |
Patient-reported outcomes for the phase 3 TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. |
Abstract #4070 Poster Session Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary June 4, 2022 8:00am (CDT) |
Vogel, A |
Regional subgroup analysis of the phase 3 TOPAZ-1 study of durvalumab (D) plus gemcitabine and cisplatin (GC) in advanced biliary tract cancer (BTC). |
Abstract #4075 Poster Session Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary June 4, 2022 8:00am (CDT) |
Özgüroğlu, M |
Adverse events self-reported by patients (pts) with extensive-stage small cell lung cancer (ES-SCLC) treated with durvalumab (D) plus platinum-etoposide (EP) or EP in the CASPIAN study. |
Abstract #8571 Poster Session Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers June 6, 2022 8:00am (CDT) |
Albiges, L |
Safety and clinical activity of MEDI5752, a PD-1/CTLA-4 bispecific checkpoint inhibitor, as monotherapy in patients (pts) with advanced renal cell carcinoma (RCC): Preliminary results from an FTIH trial. |
Abstract #107 Clinical Science Symposium Bispecifics: Are Two Better Than One? June 5, 2022 10:33am (CDT) |
DNA damage response |
|
|
Pignata, S |
Maintenance olaparib in patients (pts) with platinum-sensitive relapsed ovarian cancer (PSROC) by somatic (s) or germline (g) BRCA and other homologous recombination repair (HRR) gene mutation status: Overall survival (OS) results from the ORZORA study. |
Abstract #5519 Poster Discussion Session Gynecologic Cancer June 4, 2022 4:30pm (CDT)
|
Thiery-Vuillemin, A |
Tolerability of abiraterone (abi) combined with olaparib (ola) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Further results from the phase III PROpel trial. |
Abstract #5019 Poster Discussion Session Genitourinary Cancer—Prostate, Testicular, and Penile June 6, 2022 5:26pm (CDT) |
Armstrong, AJ |
Olaparib plus abiraterone as first-line therapy in men with metastatic castration-resistant prostate cancer: Pharmacokinetics data from the PROpel trial. |
Abstract #5050 Poster Session Genitourinary Cancer—Prostate, Testicular, and Penile June 6, 2022 1:15pm (CDT) |
Eskander, RN |
Real-world effectiveness of first-line maintenance olaparib in women with BRCA-mutated advanced ovarian cancer: U.S. retrospective cohort study. |
Abstract #5518 Poster Discussion Session Gynecologic Cancer June 4, 2022 4:30pm (CDT) |
Tumor drivers and resistance |
|
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Jones, RH |
Fulvestrant plus capivasertib versus fulvestrant plus placebo after relapse or progression on an aromatase inhibitor in metastatic, estrogen receptor–positive breast cancer (FAKTION): Overall survival and updated progression-free survival data with enhanced biomarker analysis. |
Abstract #1005 Oral Abstract Session Breast Cancer—Metastatic June 4, 2022 2:39pm (CDT) |
Nakamura, A |
A phase II study of osimertinib in combination with platinum plus pemetrexed in patients with EGFR-mutated, advanced non–small cell lung cancer: The OPAL study (NEJ032C/LOGIK1801). |
Abstract #9097 Poster Session Lung Cancer—Non-Small Cell Metastatic June 6, 2022 8:00am (CDT) |
Hematology |
|
|
Sharman, JP |
Acalabrutinib ± obinutuzumab versus obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic leukemia: Five-year follow-up of ELEVATE-TN. |
Abstract #7539 Poster Session Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia June 4, 2022 8:00am (CDT) |
U.S. Important Safety Information for ENHERTU
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:
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Unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either:
- In the metastatic setting, or
- In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy
- 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 |
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Contraindications
None.
Warnings and Precautions
Interstitial Lung Disease / Pneumonitis
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 491 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, ILD occurred in 13% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 1.4% of patients treated with ENHERTU. Median time to first onset was 5.5 months (range: 1.1 to 20.8).
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 491 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 68% of patients. Eighteen percent had Grade 3 or 4 decrease in neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 6 to 664). Febrile neutropenia was reported in 1.2% 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. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. 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. 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.
Metastatic Breast Cancer
In the 491 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU 5.4 mg/kg, 13 cases (2.6%) of asymptomatic LVEF decrease were reported.
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, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF.
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 pooled safety population for patients with metastatic breast cancer reflects exposure to ENHERTU at 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) in 491 patients in DESTINY-Breast03, DESTINY-Breast01, and Study DS8201-A-J101. The median duration of treatment was 13 months (range: 0.7 to 37). In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (78%), decreased white blood cell count (74%), decreased hemoglobin (68%), decreased neutrophil count (68%), increased aspartate aminotransferase (58%), fatigue (57%), decreased lymphocyte count (56%), vomiting (50%), decreased platelet count (49%), increased alanine aminotransferase (48%), increased blood alkaline phosphatase (45%), alopecia (41%), constipation (35%), hypokalemia (33%), decreased appetite (32%), diarrhea (31%), musculoskeletal pain (28%), increased transaminases (27%), respiratory infection (24%), headache (21%), and abdominal pain (21%).
DESTINY-Breast03
The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast03. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 14 months (range: 0.7 to 30).
Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, interstitial lung disease, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (one patient each).
ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis. Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue.
The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), hypokalemia (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), respiratory infection (22%), headache (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%).
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