Patritumab Deruxtecan Demonstrated Clinically Meaningful and Durable Responses in Patients with EGFR-Mutated Metastatic Non-Small Cell Lung Cancer in HERTHENA-Lung01 Phase 2 Trial

On September 10, 2023 Daiichi Sankyo reported that Results from the HERTHENA-Lung01 phase 2 trial showed that patritumab deruxtecan (HER3-DXd) demonstrated clinically meaningful and durable responses in patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) following disease progression with an EGFR TKI and platinum-based chemotherapy (Press release, Daiichi Sankyo, SEP 10, 2023, View Source [SID1234635049]). These data were presented today during an oral presentation (OA05.03) at the 2023 World Conference on Lung Cancer (#WCLC23) and simultaneously published in the Journal of Clinical Oncology.

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Patritumab deruxtecan is a specifically engineered potential first-in-class HER3 directed antibody drug conjugate (ADC) designed using Daiichi Sankyo’s (TSE: 4568) proprietary DXd ADC technology.

NSCLC accounts for approximately 85% of all lung cancers – 55% having distant spread at diagnosis – with EGFR-activating mutations occurring in 14% to 38% of all NSCLC tumors worldwide.1,2,3 After disease progression following treatment with an EGFR TKI and platinum-based chemotherapy, currently available therapies offer limited efficacy, highlighting the need for new approaches to improve outcomes.3,4

A confirmed objective response rate (ORR) of 29.8% (95% CI: 23.9-36.2) was observed with patritumab deruxtecan (5.6 mg/kg) in 225 patients with EGFR-mutated NSCLC as assessed by blinded independent central review (BICR). One complete response (CR), 66 partial responses (PRs) and 99 cases of stable disease (SD) were seen. A median duration of response (DOR) of 6.4 months (95% CI: 4.9-7.8) and a disease control rate (DCR) of 73.8% (95% CI: 67.5-79.4) were observed. Median progression-free survival (PFS) was 5.5 months (95% CI: 5.1-5.9) and median overall survival (OS) was 11.9 months (95% CI: 11.2-13.1) as of snapshot data cutoff of May 18, 2023.

Efficacy outcomes were consistent across subgroups including a subset of 209 patients previously treated with a third-generation EGFR TKI and platinum-based chemotherapy. Anti-tumor activity with patritumab deruxtecan was observed across diverse mechanisms of EGFR TKI resistance and across a broad range of pretreatment tumor HER3 membrane expression.

In a subset of 30 patients with brain metastases at baseline and no prior radiotherapy treatment, an intracranial ORR of 33.3% (95% CI: 17.3-52.8%) was observed as assessed by central nervous system (CNS) BICR. In these patients, nine intracranial CRs, one intracranial PR and 13 cases of SD were seen. A CNS DOR of 8.4 months (95% CI: 5.8-9.2) was observed.

"The results from HERTHENA-Lung01 provide compelling evidence of efficacy of patritumab deruxtecan in heavily pretreated patients with advanced EGFR-mutated non-small cell lung cancer," said Helena Yu, MD, Associate Attending Physician, Memorial Sloan Kettering Cancer Center. "The clinically meaningful efficacy observed across a broad range of HER3 expression and diverse mechanisms of EGFR TKI resistance as well as the anti-tumor activity seen in patients with brain metastases, underscore the potential of patritumab deruxtecan to become an important treatment option for a population of patients with lung cancer who have limited treatment options."

"Disease progression is inevitable in patients with previously treated and relapsed metastatic EGFR-mutated non-small cell lung cancer, reinforcing the need for new and innovative treatments across diverse mechanisms of resistance," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "The results from HERTHENA-Lung01, coupled with early trial results, show that patritumab deruxtecan demonstrates clinically meaningful and durable responses, illustrating the potential of this HER3 directed antibody drug conjugate to become a new standard of care for this patient population with high unmet medical need. These data will support our ongoing discussions with health authorities including our planned submission in the U.S."

The safety profile of patritumab deruxtecan observed in HERTHENA-Lung01 was consistent with previous clinical trials with a low rate (7.1%) of treatment discontinuation due to treatment-emergent adverse events (TEAEs) at the time of primary data cutoff of November 21, 2022. Grade 3 or higher TEAEs occurred in 64.9% of patients. The most common (>5%) grade 3 or higher TEAEs were thrombocytopenia (21%), neutropenia (19%), anemia (14%), leukopenia (10%), fatigue (6%), hypokalemia (5%) and asthenia (5%). Twelve patients (5.3%) had confirmed treatment-related interstitial lung disease (ILD) as determined by an independent adjudication committee. The majority of ILD events were low grade with one grade 1 event and eight grade 2 events. Two grade 3, zero grade 4 and one grade 5 ILD event were observed.

In HERTHENA-Lung01, 51% of patients (n=115) had a history of CNS metastases; 32% (n=72) and 33% of patients (n=75) had brain or liver metastases at baseline by BICR, respectively. In the trial, 63% (n=142) and 36% (n=82) of patients had either an EGFR exon 19 deletion or exon 21 L858R mutation detected at baseline, respectively, and one patient had both.

Patients were heavily pretreated receiving a median of three prior lines of systemic therapy in the locally advanced/metastatic setting (range, 1-11), including platinum-based chemotherapy (100%), third generation EFGR TKI (93%) and immunotherapy (40%). As of the snapshot data cutoff of May 18, 2023, the median trial duration was 18.9 (14.9-27.5) months, and 13 patients were continuing to receive patritumab deruxtecan.

Summary of HERTHENA-Lung01 Results

Efficacy Measure

Prior treatment with any EGFR TKI and platinum-based chemotherapy

n=225

Subset with prior treatment with third-generation EGFR

TKI and platinum-based chemotherapy

n=209

Confirmed ORR, % (95% CI)

29.8% (23.9-36.2)

29.2.% (23.1-35.9)

CR, n (%)

1 (0.4%)

1 (0.5%)

PR, n (%)

66 (29.3%)

60 (28.7%)

SD, n (%)

99 (44.0%)

91 (43.5%)

PD, n (%)

43 (19.1%)

41 (19.6%)

NE, n (%)

16 (7.1%)

16 (7.7%)

DCR (95% CI), %

73.8% (67.5-79.4)

72.7% (66.2-78.6)

DOR, median (95% CI), months

6.4 months (4.9-7.8)

6.4 months (5.2-7.8)

PFS, median (95% CI), months

5.5 months (5.1-5.9)

5.5 months (5.1-6.4)

OS, median (95% CI), months

11.9 months (11.2-13.1)

11.9 months (10.9-13.1)

CR, complete response; DCR, disease control rate; DOR, duration of response; NE, not evaluable; ORR, objective response rate; OS, overall survival; PR, partial response; PFS, progression-free survival; PD, progressive disease; SD, stable disease.

About HERTHENA-Lung01
HERTHENA-Lung01 is a global, multicenter, open-label, two-arm phase 2 trial evaluating the safety and efficacy of patritumab deruxtecan in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy. Patients were randomized 1:1 to receive 5.6 mg/kg (n=225) or an uptitration regimen (n=50). The uptitration arm was discontinued as the dose of 5.6 mg/kg of patritumab deruxtecan was selected following a risk-benefit analysis conducted from the phase 1 trial assessing the doses in a similar patient population.

The primary endpoint of HERTHENA-Lung01 was ORR as assessed by BICR. Secondary endpoints included duration of response, PFS, disease control rate, and time to response – all assessed by both BICR and investigator assessment – as well as investigator-assessed ORR, OS, safety and tolerability.

The data presented at WCLC is from the first arm and based on the fixed-dose (5.6 mg/kg) regimen.

HERTHENA-Lung01 enrolled patients in Asia, Europe, North America and Oceania. For more information about the trial, visit ClinicalTrials.gov.

About EGFR-Mutated Non-Small Cell Lung Cancer
Lung cancer is the second most common cancer and the leading cause of cancer-related deaths worldwide.5 NSCLC accounts for approximately 85% of all lung cancers – 55% having distant spread at diagnosis – with EGFR mutations occurring in 14% to 38% of all NSCLC tumors worldwide.1,2,3

The introduction of targeted therapies has improved the treatment landscape for patients with EGFR-mutated locally advanced or metastatic NSCLC. Targeted therapy with EGFR TKIs offers higher response rates, PFS and potential OS advantage, compared to chemotherapy, with third generation EGFR TKIs demonstrating superior efficacy compared to earlier generation inhibitors.1 However, disease progression from resistance to EGFR TKIs inevitably occurs one to two years following initial treatment.6

After failure of EGFR TKI and platinum-based chemotherapy, currently available therapies offer limited efficacy.3,4 A recent real-world analysis of the treatment of patients in this setting showed that the median PFS in this setting is 3.3 months (95% CI: 2.8-4.4) and median OS is 8.6 months (95% CI: 7.4-9.8). An estimated real-world ORR of 14.1% (95% CI: 3.7%-33.1%) also has been observed.7,8 New treatment approaches are needed to help improve clinical outcomes in patients with EGFR-mutated NSCLC.

About HER3
HER3 is a member of the EGFR family of receptor tyrosine kinases.9 It is estimated that about 83% of primary NSCLC tumors and 90% of advanced EGFR-mutated tumors express HER3 after prior EGFR TKI treatment.10,11 There is currently no HER3 directed therapy approved for the treatment of any cancer.

About Patritumab Deruxtecan
Patritumab deruxtecan (HER3-DXd) is an investigational HER3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, patritumab deruxtecan is composed of a fully human anti-HER3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Patritumab deruxtecan was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration in December 2021 for the treatment of patients with EGFR-mutated locally advanced or metastatic NSCLC with disease progression on or after treatment with a third-generation TKI and platinum-based therapies.

Patritumab deruxtecan is currently being evaluated as both a monotherapy and in combination with other therapies in a global development program, which includes HERTHENA-Lung02, a phase 3 trial versus platinum-based chemotherapy in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression on or after treatment with a third-generation EGFR TKI; a phase 1 trial in combination with osimertinib in EGFR-mutated locally advanced or metastatic NSCLC; and a phase 1 trial in previously treated patients with advanced NSCLC. A phase 1/2 trial in HER3 expressing metastatic breast cancer also has been completed.

Ifinatamab Deruxtecan Continues to Demonstrate Durable Responses in Patients with Advanced Small Cell Lung Cancer in Early Trial

On September 10, 2023 Daiichi Sankyo reported Updated results from a subgroup analysis of a phase 1/2 trial showed that ifinatamab deruxtecan (I-DXd) continues to demonstrate durable responses in patients with heavily pretreated advanced small cell lung cancer (SCLC) (Press release, Daiichi Sankyo, SEP 10, 2023, View Source [SID1234635048]). These data were presented today during an oral presentation (OA05.05) at the 2023 World Conference on Lung Cancer (#WCLC23) hosted by the International Association for the Study of Lung Cancer.

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Ifinatamab deruxtecan is a specifically engineered potential first-in-class B7-H3 directed antibody drug conjugate (ADC) designed using Daiichi Sankyo’s (TSE: 4568) proprietary DXd ADC technology.

Lung cancer is the second most common cancer worldwide and SCLC represents about 15% of all cases.1,2 Approximately 65% of all SCLC tumors have a moderate-to-high expression of B7-H3, which is associated with disease progression and lower survival.2,3,4

A confirmed objective response rate (ORR) of 52.4% (95% CI: 29.8-74.3) was observed in 21 patients with advanced SCLC receiving ifinatamab deruxtecan (6.4 to 16.0 mg/kg) in the dose escalation part of the phase 1/2 trial. One complete response (CR) and 10 partial responses (PRs) were seen. A median duration of response (DOR) of 5.9 months (95% CI: 2.8-7.5) was observed. Median progression-free survival (PFS) was 5.6 months (95% CI: 3.9-8.1) and median overall survival (OS) was 12.2 months (95% CI: 6.4-NA) as of data cutoff of January 31, 2023.

Tumor reduction seen with ifinatamab deruxtecan was observed across a broad range of B7-H3 protein expression levels and no apparent trend of correlation between clinical efficacy parameters and B7-H3 protein expression was observed.

"With limited effective treatment options beyond traditional chemotherapy and immunotherapy, small cell lung cancer can be difficult to treat," said Melissa Johnson, MD, Director, Lung Cancer Research, Sarah Cannon Research Institute. "The high response rate, along with the fact that all patients except one experienced a reduction in tumor size with ifinatamab deruxtecan, is promising."

The safety profile of ifinatamab deruxtecan in patients with SCLC was consistent with previous reports in the overall population of this phase 1/2 trial. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 36.4% of patients. The most common (>20%) TEAEs occurring in patients were nausea (59.1%), fatigue (50.0%), anemia (27.3%), vomiting (27.3%) and decreased appetite (22.7%). There was one grade 2 event confirmed to be treatment-related interstitial lung disease (ILD) or pneumonitis as determined by an independent adjudication committee. There was one grade 5 event of COVID-19 pneumonia that was determined not to be treatment related.

"In addition to the response rate seen with ifinatamab deruxtecan, we are further encouraged by the median overall survival seen in these patients at approximately one year," said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. "Additional evaluation of this B7-H3 directed antibody drug conjugate is underway in our ongoing phase 2 trial in patients with previously treated extensive-stage small cell lung cancer and we look forward to learning these results."

In the subset of patients with SCLC, two patients (9.1%) had brain metastases at baseline. Patients were heavily pretreated receiving a median of two prior lines of systemic therapy in the locally advanced/metastatic setting (range, 1-7), including platinum-based chemotherapy (100%), immunotherapy (81.8%), taxane chemotherapy (22.7%) and irinotecan or topotecan chemotherapy (22.7%). The median duration of follow up was 11.7 months (95% CI: 4.63-12.88) and two patients remain on treatment with ifinatamab deruxtecan.

Summary of SCLC Subset Analysis of Phase 1/2 Trial

Efficacy Measure

Patients with SCLC receiving doses of ifinatamab deruxtecan

(between 6.4 and 16.0 mg/kg)

n=21

Confirmed ORR, % (95% CI)

52.4% (29.8-74.3)
CR, n (%)

1 (4.8%)
PR, n (%)

10 (47.6%)
DOR, median (95% CI), months

5.9 months (2.8-7.5)
PFS, median (95% CI), months

5.6 months (3.9-8.1)
OS, median (95% CI), months

12.2 months (6.4-NA)
CR, complete response; DOR, duration of response; NA, not applicable; ORR, objective response rate; OS, overall survival; PR, partial response; PFS, progression-free survival.

About the Phase 1/2 Trial
The phase 1/2 trial is the first-in-human, open-label study evaluating the safety, tolerability and preliminary activity of ifinatamab deruxtecan in adult patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerable to standard treatment or for whom no standard treatment exists.

The phase 1 part of the trial (dose escalation) is assessing the safety and tolerability of increasing doses of ifinatamab deruxtecan to determine the maximum tolerated dose or recommended dose for expansion (RDE). This portion of the trial enrolled approximately 100 patients with advanced/unresectable or metastatic SCLC, squamous non-small cell lung cancer (NSCLC), metastatic castration-resistant prostate cancer (CRPC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma, bladder cancer, sarcoma, endometrial cancer, melanoma or breast cancer.

The phase 2 part of the trial (dose expansion) is evaluating the safety, tolerability and preliminary activity of ifinatamab deruxtecan in patients with squamous NSCLC, metastatic CRPC or ESCC.

The dose escalation part of the trial is evaluating dose-limiting toxicity and safety. The dose expansion part of the trial is evaluating ORR, DOR, disease control rate, PFS, OS and safety. Pharmacokinetic endpoints, exploratory biomarker and immunogenicity endpoints also will be assessed.

Patient enrollment in the ESCC and squamous NSCLC cohorts of the dose expansion part of the trial remains underway in Asia and North America. For more information, please visit ClinicalTrials.gov.

About Small Cell Lung Cancer
Lung cancer is the second most common cancer and the leading cause of cancer-related deaths worldwide.1 The two main types of lung cancer include NSCLC, which represents more than 80 to 85% of all cases, and SCLC, which comprises about 15% of cases.2 The five-year survival rate is only 3% for patients diagnosed with advanced SCLC.5

About B7-H3
B7-H3 is a transmembrane protein that belongs to the B7 family, which also includes PD-L1.6 B7-H3 is overexpressed in a wide range of cancer types, including lung, prostate and esophageal, and its overexpression has been shown to correlate with poor prognosis in some cancers, making B7-H3 a promising therapeutic target.2,4,7,8,9,10 There are no B7-H3 directed medicines approved for the treatment of any cancer.

About Ifinatamab Deruxtecan
Ifinatamab deruxtecan (I-DXd) is an investigational potential first-in-class B7-H3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Ifinatamab deruxtecan is being evaluated in a global development program, which includes IDeate-01, a phase 2 monotherapy trial in patients with previously treated extensive-stage SCLC, and a phase 1/2 first-in-human trial in collaboration with Sarah Cannon Research Institute.

About the DXd ADC Portfolio of Daiichi Sankyo
The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development across multiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, are being jointly developed and commercialized globally with AstraZeneca. Four additional Daiichi Sankyo DXd ADCs include patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd; DS-7300), a B7-H3 directed ADC, raludotatug deruxtecan (R-DXd; DS-6000), a CDH6 directed ADC, and DS-3939, a TA-MUC1 directed ADC.

Designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.

Dizal Announces Clinical Results of Golidocitinib Published in Annals of Oncology

On September 10, 2023 Dizal reported the publication of the Phase I clinical data of golidocitinib for the treatment of relapsed or refractory (r/r) peripheral T cell lymphomas (PTCL) (JACKPOT8 PARTA) in Annals of Oncology (2022-2023 Impact Factor: 51.8) (Press release, Dizal Pharma, SEP 10, 2023, View Source [SID1234635047]).

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PTCL is an aggressive non-Hodgkin lymphoma (NHL) that represents approximately 7% to 10% of NHLs worldwide. Patients with r/r PTCL face a poor prognosis, with a 3-year survival rate ranging from 21% to 28%. Currently, there is no established consensus on the standard approach for treating r/r PTCL. Therefore, there is an urgent medical need for novel and innovative treatment options to improve survival of this patient population.

Dizal identified that JAK/STAT pathway may mediate the pathogenesis of PTCL and launched clinical studies of golidocitinib to test the hypothesis. Golidocitinib is the first and currently the only Janus kinase 1 (JAK1) selective inhibitor for treating r/r PTCLs at the stage of pivotal clinical development. Consistent with earlier data, golidocitinib demonstrated potent and durable anti-tumor efficacy in the pivotal study (JACKPOT8 PARTB), with the clinical results selected as oral presentation at 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and 2023 International Conference on Malignant Lymphoma (ICML).

The primary endpoint of the study, objective response rate (ORR) assessed by an independent review committee (IRC), reached 44.3%, with a complete response rate (CRR) of 23.9%. More than 50% of the patients with tumor remission achieved a complete response. Anti-tumor efficacy was observed across different PTCL subtypes and irrespective of the patients’ prior treatment history. The median duration of response (mDoR) has not been reached. The longest DoR was 16.8 months, and the patient is still responding.

As a potent JAK1 inhibitor with > 200 to 400-fold selectivity over other JAK family members, golidocitinib demonstrated a favorable safety profile. The majority of treatment-related adverse events (TRAEs) could be monitored and well managed in the clinic. The median relative dose intensity was 100%. (Data cut-off date: February 16, 2023)

Golidocitinib was granted Fast Track Designation for the treatment of r/r PTCL by the U.S. FDA in February 2022. Furthermore, the clinical significance of golidocitinib has been widely acknowledged at prestigious conferences such as ASCO (Free ASCO Whitepaper), European Hematology Association (EHA) (Free EHA Whitepaper), ICML, and American Society of Hematology (ASH) (Free ASH Whitepaper) with five oral presentations for four consecutive years.

About Annals of Oncology

Annals of Oncology (2022-2023 Impact Factor: 51.8), the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, provides rapid and efficient peer-review publications on innovative cancer treatments or translational work related to oncology and precision medicine.

About golidocitinib (DZD4205)

Golidocitinib is the first-in-class Janus kinase 1 (JAK1) only inhibitor currently being evaluated in a global, multicenter pivotal study (JACKPOT8 PARTB) in r/r PTCL. At the data cut-off date of February 16, 2023, Golidocitinib has demonstrated robust and durable anti-tumor activity, with an ORR of 44.3% and a CRR of 23.9%. More than 50% of the patients with tumor remission achieved a complete response. The median relative dose intensity was 100%. Golidocitinib was granted Fast Track Designation by the U.S. FDA for the treatment of r/r PTCL in February 2022.

Gilead’s Phase 2 EVOKE-02 Study Of Trodelvy® (Sacituzumab Govitecan-Hziy) In Combination With KEYTRUDA® (Pembrolizumab) Demonstrates Promising Clinical Activity In First-Line Metastatic Non-Small Cell Lung Cancer

On September 10, 2023 Gilead Sciences, Inc. (Nasdaq: GILD) reported promising early data from the global, open-label, Phase 2 EVOKE-02 study evaluating Trodelvy (sacituzumab govitecan-hziy) in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) with or without platinum agents in patients with previously untreated advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations (Press release, Gilead Sciences, SEP 10, 2023, View Source [SID1234635046]). The results are being presented today at the IASLC 2023 World Conference on Lung Cancer (#WCLC23) hosted by the International Association for the Study of Lung Cancer.

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The preliminary analysis of the EVOKE-02 study includes results of two cohorts: Trodelvy in combination with KEYTRUDA in first-line advanced or metastatic squamous/non-squamous NSCLC with PD-L1 tumor proportion score (TPS) ≥ 50% (Cohort A) and TPS < 50% (Cohort B). In Cohort A (n=29), confirmed and unconfirmed objective response rate (ORR) was 69%, and disease control rate (DCR) was 86%. In Cohort B (n=32), confirmed and unconfirmed ORR was 44%, and DCR was 78%. Across both cohorts, the ORR was 56%, and DCR was 82%. Median duration of response (DoR) was not reached at the time of data cut-off, and DoR rate at six months was 88% in both cohorts.

"Patients with metastatic NSCLC continue to need novel treatment options. The data from the EVOKE-02 study gives us confidence in the clinical activity of sacituzumab govitecan in combination with pembrolizumab in first-line metastatic NSCLC patients," said Byoung Chul Cho, MD, PhD, Professor in the Division of Medical Oncology at Yonsei Cancer Center, Yonsei University College of Medicine. "The positive response rates and duration of response across patients treated with the combination shows promise compared with historical responses to anti-PD1 monotherapy in this setting.These data support further investigation of sacituzumab govitecan as a potential IO-combination option in first-line metastatic NSCLC."

"The EVOKE-02 trial is the first data presented from several Gilead studies dedicated to exploring Trodelvy’s potential in lung cancer," said Bill Grossman, MD, PhD, Senior Vice President, Therapeutic Area Head, Gilead Oncology. "These data are very encouraging and confirms our approach for the ongoing Phase 3 EVOKE-03 study of Trodelvy in combination with KEYTRUDA vs. KEYTRUDA monotherapy for patients in first-line PD-L1-high metastatic NSCLC. We look forward to potentially bringing a new treatment option to previously untreated metastatic NSCLC patients."

The safety profile of Trodelvy in combination with KEYTRUDA in the EVOKE-02 study was consistent with the known safety of each agent. The most common any-grade TEAEs were diarrhea (54%), anemia (48%), and asthenia (38%). Known key safety events for Trodelvy were not increased with the addition of KEYTRUDA. The immune related adverse events were consistent with the known safety profile of KEYTRUDA. Discontinuation rates due to adverse events were 18%. One treatment related death was observed due to sepsis.

Gilead entered into two clinical trial collaboration and supply agreements with Merck (known as MSD outside of the United States and Canada) in January 2022 to evaluate the combination of Trodelvy and Merck’s KEYTRUDA in the Phase 2 EVOKE-02 signal-seeking study and the ongoing Phase 3 EVOKE-03 study in first-line NSCLC.

The use of Trodelvy for the treatment of NSCLC and the use of Trodelvy in combination with KEYTRUDA for any use is investigational, and the safety and efficacy for these uses have not been established or approved by any regulatory agency globally. Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information.

About Metastatic Non-Small Cell Lung Cancer

Worldwide, more than two million people were diagnosed with lung cancer in 2020. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for up to 85% of diagnoses. It is a cancer with high Trop-2 expression (89 – 100%) and about half of NSCLC cases are diagnosed at the metastatic stage (57%), when treatment is especially difficult. Even in patients whose disease is caught early, half will eventually progress to the metastatic stage within five years. Newly diagnosed patients have several treatment options including platinum-based therapy, checkpoint inhibitors and targeted therapies.

About the EVOKE-02 Study

The EVOKE-02 study is an open-label, global, multi-center, multi-cohort, Phase 2 study evaluating Trodelvy in combination with KEYTRUDA with or without chemotherapy regardless of PD-L1 expression in patients with advanced or metastatic NSCLC without actionable genomic alterations. Patients were assigned to cohorts according to disease status or PD-L1 expression. Patients were assigned to Cohorts A or B according to Tumor Proportion Score (TPS) status:

Cohort A enrolled patients with squamous/non-squamous NSCLC with TPS ≥ 50%.
Cohort B enrolled patients with squamous/non-squamous NSCLC with TPS < 50%.
Patients enrolled in Cohorts A or B received the combination of Trodelvy and KEYTRUDA.

Following enrolment in a safety run-in cohort, patients will be enrolled in Cohorts C or D according to disease status for carboplatin combinations.

Cohort C enrolled patients with non-squamous NSCLC with any PD-L1 expression level.
Cohort D enrolled patients with squamous NSCLC with any PD-L1 expression level.
Patients enrolled in Cohorts C or D received Trodelvy plus KEYTRUDA plus platinum agent.

The primary endpoints are objective response rate (ORR) as assessed by independent review per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and percentage of participants experiencing dose-limiting toxicities (DLTs) per dose level in the safety run-in cohorts. Additional efficacy measures include progression-free survival (PFS), overall survival (OS), duration of response (DoR) and disease control rate (DCR). More information about EVOKE-02 is available at View Source

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About Trodelvy

Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2 directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and bladder cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the microenvironment.

Trodelvy is approved in almost 50 countries, with multiple additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.

Trodelvy is also approved in the U.S. and the European Union to treat certain patients with pre-treated HR+/HER2- metastatic breast cancer. In the U.S., Trodelvy also has accelerated approval for treatment of certain patients with second-line metastatic urothelial cancer (UC); see below for the full U.S. indication for Trodelvy.

Trodelvy is also being developed for potential investigational use in other TNBC, HR+/HER2- and metastatic UC populations, as well as a range of tumor types where Trop-2 is highly expressed, including metastatic non-small cell lung cancer (NSCLC), metastatic small cell lung cancer (SCLC), head and neck cancer, and endometrial cancer.

U.S. Indications for Trodelvy

In the United States, Trodelvy is indicated for the treatment of adult patients with:

Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
Locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. 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 confirmatory trials.
U.S. Important Safety Information for Trodelvy

BOXED WARNING: NEUTROPENIA AND DIARRHEA

Severe or life-threatening neutropenia may occur. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold Trodelvy until resolved to ≤Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS

Severe hypersensitivity reaction to Trodelvy.
WARNINGS AND PRECAUTIONS

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 64% of patients treated with Trodelvy. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold Trodelvy for neutropenic fever. Administer G-CSF as clinically indicated or indicated in Table 1 of USPI.

Diarrhea: Diarrhea occurred in 64% of all patients treated with Trodelvy. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold Trodelvy for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with Trodelvy. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of Trodelvy was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue Trodelvy for Grade 4 infusion-related reactions.

Nausea and Vomiting: Nausea occurred in 64% of all patients treated with Trodelvy and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold Trodelvy doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with Trodelvy. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue Trodelvy based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, Trodelvy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Trodelvy contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Trodelvy and for 3 months after the last dose.

ADVERSE REACTIONS

In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%).

In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes.

In the TROPHY study (locally advanced or metastatic urothelial cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, any infection, alopecia, decreased appetite, constipation, vomiting, rash, and abdominal pain. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY study were reduced neutrophils, leukocytes, and lymphocytes.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of Trodelvy with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with Trodelvy.

UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy.

Please see full Prescribing Information , including BOXED WARNING.

Datopotamab deruxtecan plus Imfinzi showed promising clinical activity in the first-line advanced non-small cell lung cancer setting in TROPION-Lung04 Phase Ib trial

On September 10, 2023 Astrazeneca and Daiichi Sankyo reported that Initial results from the TROPION-Lung04 Phase Ib trial showed datopotamab deruxtecan (Dato-DXd) in combination with Imfinzi (durvalumab), an anti-PD-L1 therapy, with or without carboplatin demonstrated encouraging responses and no new safety signals in patients with previously untreated advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations (Press release, AstraZeneca, SEP 10, 2023, View Source [SID1234635045]).

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These data were presented today in a late-breaking oral presentation (#OA05.06) at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (WCLC).

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.

More than one million people worldwide are diagnosed with advanced NSCLC each year.1,2 While 1st-line treatment with immune checkpoint inhibitors with or without chemotherapy has improved outcomes for patients with NSCLC without actionable genomic alterations, like EGFR or ALK, most patients eventually experience disease progression.3-5 TROP2 is a protein broadly expressed in a large majority of NSCLC tumours.6 There are currently no TROP2-directed ADCs approved for the treatment of patients with lung cancer.7,8

In previously untreated patients, datopotamab deruxtecan plus durvalumab (doublet; n=14) demonstrated an objective response rate (ORR) of 50.0%, including 7 partial responses (PR), and a disease control rate (DCR) of 92.9%. Response rates were higher in patients receiving datopotamab deruxtecan plus durvalumab and carboplatin (triplet; n=13) which demonstrated an ORR of 76.9%, including 10 PRs, and a DCR of 92.3%. Responses were observed across PD-L1 expression levels.

Saiama Waqar, MD, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, and investigator in the trial, said: "Most patients with advanced non-small cell lung cancer experience disease progression after initial treatment, underscoring the need for more effective first-line treatment options. The TROPION-Lung04 results offer preliminary evidence for the efficacy of datopotamab deruxtecan in combination with durvalumab and chemotherapy in first-line advanced non-small cell lung cancer with no new safety signals. We eagerly await enrolment and results from the Phase III programme evaluating various datopotamab deruxtecan and immune checkpoint inhibitor combinations in this setting."

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: "Following the positive high-level results of TROPION-Lung01, these initial TROPION-Lung04 results in the first-line setting reinforce our confidence in datopotamab deruxtecan as a potential treatment option for patients with advanced non-small cell lung cancer. Through our robust clinical programme we are eager to continue evaluating this TROP2-directed antibody drug conjugate in lung cancer across treatment settings, alone and in novel combinations."

Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo, said: "These early trial results further demonstrate the potential for datopotamab deruxtecan to enhance response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer and without actionable genomic alterations. We look forward to continuing to evaluate this promising TROP2-directed antibody drug conjugate in multiple ongoing Phase III trials to address what has long been an unmet need for the lung cancer community across treatment settings."

In both previously treated and untreated patients, the safety profiles of datopotamab deruxtecan and Imfinzi with and without carboplatin were consistent with other clinical trials and with the known safety profile of each agent. Grade 3 or greater treatment-emergent adverse events (TEAEs) occurred in 42.1% of patients receiving doublet therapy and 71.4% of patients receiving triplet therapy. In patients receiving triplet therapy, the most common Grade 3 or greater TEAEs (occurring in more than 15% of patients) were anaemia (36%) and thrombocytopenia (21%). No Grade 3 or greater TEAE occurred in more than 15% of patients receiving doublet therapy. Across treatment cohorts, there were four interstitial lung disease (ILD) events adjudicated as drug-related by an independent committee including one Grade 1 event, two Grade 2 events and one Grade 4 event. No Grade 5 ILD events were observed.

Summary of TROPION-Lung04 Efficacy Results

Responses in Previously Untreated Patients

Doublet Therapy

(Cohort 2; n=14)

Triplet Therapy

(Cohort 4; n=13)

ORR (confirmed and pending), %i (95% CI)

50.0% (23.0-77.0; n=7)

76.9% (46.2-95.0; n=10)

CR, %

0%

0%

PR, %

50.0% (n=7)

76.9% (n=10) ii

SD, %

42.9% (n=6)

15.4% (n=2)

PD, %

7.1% (n=1)

7.7% (n=1)

DCR, % iii

92.9% (66.1-99.8; n=13)

92.3% (64.0-99.8; n=12)

CI, confidence interval; CR, complete response; DCR, disease control rate; ORR, objective response rate; PR, partial response; PD, progressive disease; SD, stable disease
i ORR is CR + PR
ii One of the 10 partial responses in Cohort 4 was confirmed after data cut-off
ii iDCR is best overall response of confirmed CR + confirmed PR + SD

In the doublet cohort, 73.7% (n=14 of 19) of patients were previously untreated. In the triplet cohort, 92.9% (n=13 of 14) of patients were previously untreated. Both the doublet and triplet cohorts included patients with PD-L1 expression levels ranging from less than 1% (n=6, 6), 1-49% (n=6, 3) and 50% or greater (n=7, 5). As of the 6 March 2023 data cut-off, median study duration was six months for both cohorts and treatment was ongoing in 31.6% and 50.0% of patients in the doublet and triplet cohorts, respectively.

AstraZeneca and Daiichi Sankyo have three Phase III trials evaluating datopotamab deruxtecan-based combinations as potential 1st-line treatment options for patients with advanced or metastatic NSCLC without actionable genomic alterations compared to the respective standard of care for the patient population of each study.

AVANZAR is evaluating datopotamab deruxtecan plus Imfinzi and carboplatin in patients regardless of PD-L1 expression or tumour histology.
TROPION-Lung07 is evaluating datopotamab deruxtecan plus pembrolizumab with or without chemotherapy in patients with non-squamous disease and PD-L1 expression less than 50%.
TROPION-Lung08 is evaluating datopotamab deruxtecan plus pembrolizumab in patients with PD-L1 expression of 50% or greater.
Notes

Non-small cell lung cancer
More than one million people worldwide are diagnosed with advanced NSCLC each year.1,2 While targeted therapies and immune checkpoint inhibitors have improved patient outcomes, advanced NSCLC has a poor prognosis and is associated with worsening outcomes after each line of subsequent therapy.3-5

Most patients with NSCLC have tumours that do not express a known actionable genomic alteration (e.g., EGFR, ALK, ROS1, NTRK, BRAF, RET or MET).9-11 The current 1st-line standard of care for these patients is immune checkpoint inhibitors with or without platinum-based chemotherapy. Approximately 40-60% of tumours will not respond to this initial treatment and while these therapies may improve survival for patients whose tumours do respond, most will experience disease progression.5,7

TROP2, a transmembrane glycoprotein, is broadly expressed in a large majority of NSCLC tumours.6 There are currently no TROP2-directed ADCs approved for the treatment of lung cancer.

TROPION-Lung04
TROPION-Lung04 is an ongoing global, open-label, 11-cohort Phase Ib trial evaluating the efficacy and safety of datopotamab deruxtecan (4 mg/kg or 6 mg/kg) in combination with immunotherapy (Imfinzi, AZD2936 or MEDI5752) with or without up to four cycles of carboplatin in patients with advanced or metastatic NSCLC without actionable genomic alterations. Patients enrolled in the cohorts evaluating Imfinzi were previously untreated or had received one or fewer lines of systemic chemotherapy without concomitant immunotherapy. The primary endpoints of TROPION-Lung04 are safety and tolerability. Secondary endpoints include ORR, DCR, duration of response and progression-free survival as assessed by investigator. TROPION-Lung04 will enrol approximately 230 patients globally.

Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of five lead ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

A comprehensive development programme is underway globally with more than 12 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple TROP2-targetable tumours, including NSCLC, triple-negative breast cancer and hormone receptor-positive, HER2-negative breast cancer. Beyond the TROPION programme, datopotamab deruxtecan is also being evaluated in novel combinations in several ongoing trials. AstraZeneca is also researching a potential diagnostic test to help identify patients most likely to benefit from treatment with datopotamab deruxtecan.

Imfinzi
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 tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiation therapy based on the PACIFIC Phase III trial.

Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage SCLC based on the CASPIAN Phase III trial. In an exploratory analysis in 2021, updated results from the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at three years versus chemotherapy alone. Additionally, Imfinzi is approved in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC in the US, EU and Japan based on the POSEIDON Phase III trial.

In addition to its indications in lung cancer, Imfinzi is also approved in combination with chemotherapy in locally advanced or metastatic biliary tract cancer in the US, EU, Japan and several other countries; in combination with Imjudo in unresectable hepatocellular carcinoma in the US, EU and Japan; and in previously treated patients with advanced bladder cancer in a small number of countries.

Since the first approval in May 2017, more than 200,000 patients have been treated with Imfinzi.

AstraZeneca has several ongoing registrational trials focused on testing Imfinzi in earlier stages of lung cancer, including in resectable NSCLC (ADJUVANT BR.31) and unresectable NSCLC (PACIFIC-2, 4, 5, 8 and 9), and in limited-stage SCLC (ADRIATIC).

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several gastrointestinal (GI) cancers, ovarian cancer, endometrial cancer and other solid tumours.