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IMFINZI® (durvalumab) significantly improved overall survival and progression-free survival for patients with limited-stage small cell lung cancer in ADRIATIC Phase III trial

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AstraZeneca's IMFINZI shows survival benefit in Phase III trial for -stage small cell lung cancer, marking a breakthrough in treatment. Positive results in OS and PFS with no new safety signals identified. IMFINZI continues to lead in lung cancer treatment.
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The recent findings from the ADRIATIC Phase III trial indicating that IMFINZI (durvalumab) extends overall survival and progression-free survival in patients with limited-stage small cell lung cancer post concurrent chemoradiotherapy represent a significant advancement in oncology. From a medical standpoint, the improvement in survival rates is noteworthy given the aggressive nature of small cell lung cancer and its poor prognosis. The fact that IMFINZI is consistent with its known safety profile and no new safety signals were identified adds a layer of reassurance regarding the treatment's risk-benefit balance. However, it is important to continue monitoring for long-term outcomes and potential late-onset adverse effects that may not be immediately evident.

From a research perspective, the breakthrough highlighted by the ADRIATIC trial underscores the role of immunotherapy in potentially altering the treatment paradigm for early-stage lung cancer. It's important to note that the trial's dual primary endpoints being met is a robust indicator of the drug's efficacy. Additionally, the ongoing blinded study of IMJUDO (tremelimumab-actl) could further influence future treatment strategies if results show additional benefit. These developments could have implications for how new treatments are integrated into clinical guidelines and standard care practices.

For investors and stakeholders, AstraZeneca's positive trial results may translate into a competitive advantage in the oncology market, especially considering that IMFINZI is already approved for extensive-stage SCLC and unresectable Stage III NSCLC. The expansion into limited-stage SCLC could potentially increase the drug's market share and drive revenue growth. It is essential, however, to monitor how these results will affect the company's stock performance in the short term, as market reaction can be influenced by regulatory approvals, market adoption rates and potential competition from other emerging therapies.

First and only immunotherapy to demonstrate survival benefit in this setting in a global Phase III trial

WILMINGTON, Del.--(BUSINESS WIRE)-- Positive high-level results of the ADRIATIC Phase III trial showed AstraZeneca’s IMFINZI® (durvalumab) demonstrated a statistically significant and clinically meaningful improvement in the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) in patients with limited-stage small cell lung cancer (LS-SCLC) who had not progressed following concurrent chemoradiotherapy (cCRT) compared to placebo after cCRT.

Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer that typically recurs and progresses rapidly despite initial response to chemotherapy and radiotherapy in LS-SCLC patients.1,2 The prognosis is particularly poor for LS-SCLC, as only 15-30% of these patients will be alive five years after diagnosis.3

Suresh Senan, PhD, Professor of Clinical Experimental Radiotherapy at the Amsterdam University Medical Center, The Netherlands, and principal investigator in the trial said: “Many patients treated for limited-stage small cell lung cancer face disease recurrence and the standard of care has remained unchanged for decades. ADRIATIC is the first global Phase III immunotherapy trial to deliver significant, clinically meaningful improvement in survival in this setting, marking a breakthrough for patients with this devastating disease.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “These exciting results build on the transformative efficacy of IMFINZI in extensive-stage small cell lung cancer and demonstrate the potential to bring a curative-intent immunotherapy treatment to this earlier-stage setting of small cell lung cancer for the first time. These data, together with the PACIFIC data in unresectable, Stage III non-small cell lung cancer, underscore the pioneering role of IMFINZI in the treatment of early lung cancer following chemoradiotherapy.”

The safety profile for IMFINZI was consistent with its known profile, and no new safety signals were identified.

These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.

The second experimental arm testing the efficacy of IMJUDO® (tremelimumab-actl) added to IMFINZI as a secondary endpoint remains blinded and will continue to the next planned analysis.

IMFINZI is approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage SCLC (ES-SCLC) based on the CASPIAN Phase III trial. IMFINZI is also the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after CRT based on the PACIFIC Phase III trial.

IMPORTANT SAFETY INFORMATION

There are no contraindications for IMFINZI® (durvalumab) or IMJUDO® (tremelimumab-actl).

Severe and Fatal Immune-Mediated Adverse Reactions

Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI and IMJUDO depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI and IMJUDO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation.

  • IMFINZI as a Single Agent
    • In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions.
    • The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC or BTC when given in combination with chemotherapy.
  • IMFINZI with IMJUDO
    • Immune‑mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.5%), and Grade 3 (1%) adverse reactions.

Immune-Mediated Colitis

IMFINZI with IMJUDO and platinum-based chemotherapy can cause immune-mediated colitis, which may be fatal.

IMFINZI and IMJUDO can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

  • IMFINZI as a Single Agent
    • Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions.
  • IMFINZI with IMJUDO
    • Immune‑mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%) adverse reactions. Intestinal perforation has been observed in other studies of IMFINZI and IMJUDO.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated colitis occurred in 6.5% (39/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including fatal (0.2%) and Grade 3 (2.5%) adverse reactions. Intestinal perforation and large intestine perforation were reported in 0.1% of patients.

Immune-Mediated Hepatitis

IMFINZI and IMJUDO can cause immune-mediated hepatitis, which may be fatal.

  • IMFINZI as a Single Agent
    • Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions.
  • IMFINZI with IMJUDO
    • Immune‑mediated hepatitis occurred in 7.5% (29/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4 (0.3%) and Grade 3 (4.1%) adverse reactions.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated hepatitis occurred in 3.9% (23/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.3%), Grade 4 (0.5%), and Grade 3 (2%) adverse reactions.

Immune-Mediated Endocrinopathies

  • Adrenal Insufficiency: IMFINZI and IMJUDO can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated.
    • IMFINZI as a Single Agent
      • Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
    • IMFINZI with IMJUDO
      • Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions.
    • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
      • Immune-mediated adrenal insufficiency occurred in 2.2% (13/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.8%) adverse reactions.
  • Hypophysitis: IMFINZI and IMJUDO can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated.
    • IMFINZI as a Single Agent
      • Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI.
    • IMFINZI with IMJUDO
      • Immune-mediated hypophysitis/hypopituitarism occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO.
    • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
      • Immune-mediated hypophysitis occurred in 1.3% (8/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions.
  • Thyroid Disorders (Thyroiditis, Hyperthyroidism, and Hypothyroidism): IMFINZI and IMJUDO can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.
    • IMFINZI as a Single Agent
      • Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
      • Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI.
      • Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
    • IMFINZI with IMJUDO
      • Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO.
      • Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions.
      • Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI and IMJUDO.
    • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
      • Immune-mediated thyroiditis occurred in 1.2% (7/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy.
      • Immune-mediated hyperthyroidism occurred in 5% (30/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions.
      • Immune-mediated hypothyroidism occurred in 8.6% (51/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions.
  • Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated.
    • IMFINZI as a Single Agent
      • Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI.
    • IMFINZI with IMJUDO
      • Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up.
    • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
      • Immune-mediated Type 1 diabetes mellitus occurred in 0.5% (3/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including Grade 3 (0.3%) adverse reactions.

Immune-Mediated Nephritis with Renal Dysfunction

IMFINZI and IMJUDO can cause immune-mediated nephritis.

  • IMFINZI as a Single Agent
    • Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
  • IMFINZI with IMJUDO
    • Immune-mediated nephritis occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.5%) adverse reactions.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated nephritis occurred in 0.7% (4/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions.

Immune-Mediated Dermatology Reactions

IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 and CTLA-4 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.

  • IMFINZI as a Single Agent
    • Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions.
  • IMFINZI with IMJUDO
    • Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions.

Immune-Mediated Pancreatitis

IMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions.

Other Immune-Mediated Adverse Reactions

The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI and IMJUDO or were reported with the use of other immune-checkpoint inhibitors.

  • Cardiac/vascular: Myocarditis, pericarditis, vasculitis.
  • Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy.
  • Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
  • Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.
  • Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic.
  • Endocrine: Hypoparathyroidism.
  • Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection.

Infusion-Related Reactions

IMFINZI and IMJUDO can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI and IMJUDO based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses.

  • IMFINZI as a Single Agent
    • Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.
  • IMFINZI with IMJUDO
    • Infusion-related reactions occurred in 10 (2.6%) patients receiving IMFINZI and IMJUDO.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Infusion-related reactions occurred in 2.9% (17/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions.

Complications of Allogeneic HSCT after IMFINZI

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on their mechanism of action and data from animal studies, IMFINZI and IMJUDO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and IMJUDO and advise them to use effective contraception during treatment with IMFINZI and IMJUDO and for 3 months after the last dose of IMFINZI and IMJUDO.

Lactation

There is no information regarding the presence of IMFINZI and IMJUDO in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI and IMJUDO, advise women not to breastfeed during treatment and for 3 months after the last dose.

Adverse Reactions

  • In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), the most common adverse reactions (≥20%) were cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis (34%), upper respiratory tract infections (26%), dyspnea (25%), and rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonia (7%) and pneumonitis/radiation pneumonitis (3.4%).
  • In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), discontinuation due to adverse reactions occurred in 15% of patients in the IMFINZI arm. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. The most frequent serious adverse reactions (≥2%) were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in <2% of patients and were similar across arms.
  • In patients with mNSCLC in the POSEIDON study receiving IMFINZI and IMJUDO plus platinum-based chemotherapy (n=330), the most common adverse reactions (occurring in ≥20% of patients) were nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased appetite (28%), rash (27%), and diarrhea (22%).
  • In patients with mNSCLC in the POSEIDON study receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy (n=330), permanent discontinuation of IMFINZI or IMJUDO due to an adverse reaction occurred in 17% of patients. Serious adverse reactions occurred in 44% of patients, with the most frequent serious adverse reactions reported in at least 2% of patients being pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse reactions occurred in a total of 4.2% of patients.
  • In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), the most common adverse reactions (≥20%) were nausea (34%), fatigue/asthenia (32%), and alopecia (31%). The most common Grade 3 or 4 adverse reaction (≥3%) was fatigue/asthenia (3.4%).
  • In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD (1.1%). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy.
  • In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse reactions (occurring in ≥20% of patients) were fatigue (42%), nausea (40%), constipation (32%), decreased appetite (26%), abdominal pain (24%), rash (23%), and pyrexia (20%).
  • In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to adverse reactions occurred in 6% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 47% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 2% of patients were cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and acute kidney injury (2.4%). Fatal adverse reactions occurred in 3.6% of patients receiving IMFINZI plus chemotherapy. These include ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients), and upper gastrointestinal hemorrhage (2 patients).
  • In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), the most common adverse reactions (occurring in ≥20% of patients) were rash (32%), diarrhea (27%), fatigue (26%), pruritus (23%), musculoskeletal pain (22%), and abdominal pain (20%).
  • In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), serious adverse reactions occurred in 41% of patients. Serious adverse reactions in >1% of patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). Fatal adverse reactions occurred in 8% of patients who received IMJUDO in combination with durvalumab, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%). Permanent discontinuation of treatment regimen due to an adverse reaction occurred in 14% of patients.

The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients.

Indications:

IMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).

IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).

Please see Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO.

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Notes

Small cell lung cancer

Lung cancer is the leading cause of cancer death among men and women and accounts for about one-fifth of all cancer deaths.4 Lung cancer is broadly split into NSCLC and SCLC, with about 15% of cases classified as SCLC.5

LS-SCLC (Stage I-III) is classified as SCLC that is generally only in one lung or one side of the chest.6 LS-SCLC accounts for approximately 30% of SCLC diagnoses and the prognosis remains poor despite curative-intent treatment with standard-of-care cCRT.7

ADRIATIC

The ADRIATIC trial is a randomized, double-blind, placebo-controlled, multi-center global Phase III trial evaluating IMFINZI monotherapy and IMFINZI plus IMJUDO versus placebo in the treatment of 730 patients with LS-SCLC who had not progressed following cCRT. In the experimental arms, patients were randomized to receive a 1500mg fixed dose of IMFINZI with or without IMJUDO 75mg every four weeks for up to four doses/cycles each, followed by IMFINZI every four weeks for up to 24 months.

The dual primary endpoints are PFS and OS for IMFINZI monotherapy versus placebo. Key secondary endpoints included OS and PFS for IMFINZI plus IMJUDO versus placebo, safety and quality of life measures. The trial includes 164 centers in 19 countries across North and South America, Europe and Asia.

IMFINZI® (durvalumab)

IMFINZI® (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.

In addition to its indications in unresectable, Stage III NSCLC and ES-SCLC, IMFINZI is currently approved in a number of countries in combination with a short course of IMJUDO and chemotherapy for the treatment of metastatic NSCLC.

IMFINZI is also approved in a number of countries in combination with chemotherapy in locally advanced or metastatic biliary tract cancer and in combination with IMJUDO in unresectable hepatocellular carcinoma (HCC). IMFINZI is also approved as a monotherapy in unresectable HCC in Japan and the EU and in previously treated patients with advanced bladder cancer in a small number of countries.

Since the first approval in May 2017, more than 220,000 patients have been treated with IMFINZI. As part of a broad development program, IMFINZI is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal cancers and other solid tumors.

IMJUDO® (tremelimumab-actl)

IMJUDO® (tremelimumab-actl) is a human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). IMJUDO blocks the activity of CTLA-4, contributing to T-cell activation, priming the immune response to cancer and fostering cancer cell death.

In addition to its approved indications in combination with IMFINZI in liver and lung cancers, the combination of IMJUDO and IMFINZI is being evaluated across multiple tumor types including locoregional HCC (EMERALD-3) and bladder cancer (VOLGA and NILE).

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; IMFINZI and IMJUDO; fam-trastuzumab deruxtecan-nxki 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 immuno-oncology (IO)

AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumor immune response and stimulate the body’s immune system to attack tumors.

AstraZeneca strives to redefine cancer care and help transform outcomes for patients with IMFINZI as a monotherapy and in combination with IMJUDO as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T cell engagers.

AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical program, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.

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 catalyze 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, Rare Diseases, 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. Please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca.

References

  1. National Cancer Institute. NCI Dictionary - Small Cell Lung Cancer. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer. Accessed April 2024.
  2. Qin A and Kalemkerian GP. Treatment Options for Relapsed Small-Cell Lung Cancer: What Progress Have We Made? J Oncol Pract. 2018;14(6):369-370.
  3. Bebb DG, et al. Symptoms and Experiences with Small Cell Lung Cancer: A Mixed Methods Study of Patients and Caregivers. Pulm Ther. 2023:9;435-450.
  4. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf. Accessed April 2024.
  5. LUNGevity Foundation. Types of Lung Cancer. Available at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed April 2024.
  6. American Cancer Society. Treatment Choices by Stage for Small Cell Lung Cancer. Available at: https://www.cancer.org/cancer/lung-cancer/treating-small-cell/by-stage.html. Accessed April 2024.
  7. Senan S, et al. ADRIATIC: A phase III trial of durvalumab ± tremelimumab after concurrent chemoradiation for patients with limited stage small cell lung cancer. Ann Oncol. 2019;30(suppl. 2):ii25.

US-88063 Last Updated 4/24

Media Inquiries

Brendan McEvoy +1 302 885 2677

Chelsea Tressler +1 302 885 2677

US Media Mailbox: usmediateam@astrazeneca.com

Source: AstraZeneca

FAQ

What are the high-level results of AstraZeneca's IMFINZI in the ADRIATIC Phase III trial?

The ADRIATIC Phase III trial showed that IMFINZI demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) in patients with -stage small cell lung cancer (LS-SCLC).

What is the prognosis for patients with -stage small cell lung cancer (LS-SCLC)?

The prognosis for LS-SCLC patients is poor, with only 15-30% of these patients surviving five years after diagnosis.

Who is the principal investigator in the ADRIATIC trial for IMFINZI?

Suresh Senan, PhD, is the principal investigator in the ADRIATIC Phase III trial for IMFINZI.

What is the safety profile of IMFINZI in the ADRIATIC trial?

The safety profile of IMFINZI in the ADRIATIC trial was consistent with its known profile, with no new safety signals identified.

Where is IMFINZI approved for the treatment of small cell lung cancer?

IMFINZI is approved in the US, EU, Japan, China, and many other countries worldwide for the treatment of extensive-stage small cell lung cancer (ES-SCLC).

AstraZeneca PLC

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