On June 2, 2024 Nanjing leads Biolab reported that after rigorous evaluation by Scientific Program Committee and ASCO (Free ASCO Whitepaper) Leadership, LBL-024, a bispecific antibody independently developed by Leads Biolabs with global intellectual property rights, was selected for an oral presentation (Press release, Nanjing Leads Biolabs, JUN 2, 2024, View Source [SID1234643940]). Today, Dr. Panpan Zhang, the investigator of LBL-024, presented the outstanding clinical data during the Clinical Science Symposium-Building Novel Antibody-Based Approaches in Gastrointestinal Cancers.

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This is a phase I/II first in human, open-label, multicenter, dose escalation/expansion study that evaluates the safety and efficacy of LBL-024 monotherapy in patients with advanced malignant tumors and neuroendocrine carcinoma. The study results demonstrated good safety profile and very promising antitumor effects as a monotherapy in patients with advanced malignant tumors, particularly extrapulmonary neuroendocrine carcinomas (EP-NEC) patients who failed at least one line of chemotherapy.

EP-NEC is a rare disease that typically occurs in the stomach, intestines, and pancreas. Most patients are diagnosed at a later stage when the cancer has already metastasized to other areas in the body. By then, the disease has progressed rapidly and the prognosis is extremely poor. No drug has been approved by the Regulatory Agencies for this lethal malignancy so far and the recommended treatment options for the advanced EP-NEC are very limited, especially for those who progress beyond first-line platinum-based chemotherapy. These underscore the urgency to develop novel therapeutic approaches.

According to results in the oral presentation, LBL-024 monotherapy showed good safety profile, especially mild liver toxicity in advanced solid tumors. The severity of AEs was mostly grade 1-2, no unexpected AEs were observed. At the dose of 15 mg/kg, ORR was 37.5% and DCR was 50.0% in 2nd line EP-NEC, and robust anti-tumor activities were observed in wide therapeutic dose range (0.8-15mg/kg) in EP-NEC. Median follow-up was 8.5 months, Median DoR was 5.3 months, mOS was not reached, 6-months OS rate of the overall, 2nd line, and ≥3rd line were 61.7%, 72.7% and 52.0%，respectively. 54.5% ORR in 22 patients with PD-L1 negative expression (CPS<1) were observed, which indicate patients can benefit from treatment with LBL-024 regardless of PD-L1 expression in tumor tissue.

The promising efficacy data of the LBL-024 monotherapy support continued development of LBL-024 in patients with EP-NEC. A single-arm pivotal study of LBL-024 monotherapy in EP-NEC was approved on April 30, 2024, which will help accelerate the listing process of LBL-024 (Click to view details). Currently, there are no 4-1BB-targeting drugs available both domestically and internationally. LBL-024 has First-in-Class potential and is expected to become the first approved standard treatment for EP-NEC after progression on second-line therapy, offering a more effective treatment option and providing hope for survival to patients with advanced EP-NEC.

Dr. Charles Cai, Chief Medical Officer of Leads Biolabs, said "ASCO has very strict selection criteria, and abstracts selected for oral presentation must be among the most representative studies in the field of cancer that are significant for patient treatment. Leads Biolabs adopted a differentiated, innovative, and efficient development strategy in the clinical development of LBL-024. In patients with advanced malignant tumors, particularly EP-NEC patients who failed at least one line of chemotherapy, LBL-024 has demonstrated good safety and strong efficacy signals and was recently approved to conduct an accelerated development of single-arm pivotal clinical study by China Regulatory Authority, CDE."

Dr. Xiaoqiang Kang, founder, chairman and CEO of Leads Biolabs, said" Leads Biolabs has always been committed to differentiated innovation, encompassing the development of new targets, the design of drug molecules, and clinical development strategies. From the very beginning of the project, we evaluate whether our technology and products are scientifically sound, whether they can overcome obstacles and challenges of current products, and whether they can bring better therapeutic benefits. It is this persistence that ensures our products have potential advantages, enabling them to stand out from numerous competitors. These innovative achievements, in turn, have verified the feasibility of our R&D strategy. In the future, Leads Biolabs will continue to focus on unmet medical need, persist in innovation, and look forward to innovative drugs with clinical value bringing benefits to patients as soon as possible."

About LBL-024

LBL-024 is a uniquely designed bispecific antibody composed of an anti-Programmed Cell Death Ligand-1 (PD-L1) and an anti-4-1BB (CD137) antibody. It binds to PD-L1 with high affinity, blocks the immunosuppressive pathway of tumor cells by targeting PD-L1 and effectively localizes 4-1BB co-stimulation to the tumor microenvironment. This activation of T cells exerts a powerful immune response, resulting in a potentially stronger antitumor effect than anti-PD-1/PD-L1 monoclonal antibodies alone.

On June 2, 2024 Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) reported longer-term efficacy and safety results from Arm A1 of the Phase 2 EDGE-Gastric study. These updated data show consistent objective response rate (ORR) and provide mature progression-free survival (PFS) in patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma (upper GI cancers) (Press release, Gilead Sciences, JUN 2, 2024, View Source [SID1234643936]). The ongoing, multi-arm, global Phase 2 EDGE-Gastric study is evaluating the safety and efficacy of various combinations of the Fc-silent anti-TIGIT antibody domvanalimab plus the anti-PD-1 monoclonal antibody zimberelimab and chemotherapy in this patient population. These results will be presented today during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series: Rapid Abstract Updates session by Yelena Y. Janjigian, M.D., Chief, Gastrointestinal Oncology, Memorial Sloan Kettering Cancer Center, and a principal investigator for the EDGE-Gastric study (Abstract 433248).

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"I am encouraged to see that patients treated with domvanalimab plus zimberelimab and chemotherapy had a median progression-free survival beyond one year, which exceeds the historical benchmarks for anti-PD-1 plus chemotherapy alone," said Dr. Janjigian. "Notably, nearly 60% of patients in the EDGE-Gastric study achieved progression-free survival at 12 months. These promising results reinforce our confidence in the ongoing Phase 3 STAR-221 study, which evaluates the same regimen in the same patient population and has the potential to address a high unmet need for people with these cancers."

At data cutoff (DCO, March 12, 2024), safety and efficacy were evaluated in all patients enrolled and treated (n=41). With a median time on treatment of 49.4 weeks (range: 0.4 – 79.4 weeks), the domvanalimab plus zimberelimab and chemotherapy regimen demonstrated sustained improvement across efficacy measures, including in those patients who have low PD-L1 expression.

Summary of efficacy results:

Endpoint

Overall*

PD-L1-high

PD-L1-low

n=41

(TAP ≥5%)

(TAP <5%)

n=16

n=24

Progression-Free Survival (PFS)

Median in Months (95% CI)

12.9 mos (9.8, 13.8)

13.8 mos (11.3, NE)

11.3 mos (5.5, 13.8)

12-month PFS Rate (95% CI)

57.6% (41.7,73.5)

68.8% (46.0, 91.5)

46.8% (24.7, 68.9)

Objective Response Rate (ORR)

per RECIST v1.1

Confirmed ORR (95% CI)

58.5% (42.1, 73.7)

68.8% (41.3, 89.0)

50.0% (29.1, 70.9)

Complete Response

3 (7.3%)

1 (6.3%)

1 (4.2%)

Partial Response

21 (51.2%)

10 (62.5%)

11 (45.8%)

Stable Disease

14 (34.1%)

5 (31.3%)

9 (37.5%)

Progressive Disease Confirmed

2 (4.9%)

0

2 (8.3%)

Not Evaluable**

1 (2.4%)

0

1 (4.2%)

Median Duration of Response (DOR) in Months

12.4 mos (9.9, NE)

NE (11.5, NE)

10.2 mos (4.0, 12.4)

*One subject with no tissue available for central PD-L1 testing. From local lab results, the subject is PD-L1 low via 22-C3 assay. This subject achieved confirmed complete response.

** One subject has no post baseline scans.

CI: confidence interval

NE: not evaluable

TAP: tumor area positivity

No unexpected safety signals were observed at the time of DCO. The domvanalimab plus zimberelimab and chemotherapy regimen was generally well tolerated and showed an overall safety profile consistent with the known safety profiles of each individual molecule to date. Infusion-related reactions were observed in 19.5% of the total subjects, and the majority were related to chemotherapy.

The updated data from Arm A1 of the Phase 2 EDGE-Gastric study support the ongoing Phase 3 STAR-221 study, in unresectable or metastatic upper GI cancers, which is expected to complete enrollment mid-year 2024.

Domvanalimab and zimberelimab are investigational molecules. Neither Gilead nor Arcus has received approval from any regulatory authority for any use of these molecules, and their safety and efficacy for the treatment of gastrointestinal cancers have not been established.

About the EDGE-Gastric Study

The ongoing, multi-arm, multi-cohort global Phase 2 EDGE-Gastric trial (NCT05329766) is evaluating the safety and efficacy of various combinations of the Fc-silent anti-TIGIT antibody domvanalimab and the anti-PD-1 monoclonal antibody zimberelimab in patients with locally advanced unresectable or metastatic gastric (G), gastroesophageal junction (GEJ) or esophageal (E) adenocarcinoma. Patients in Arm A1, with previously untreated G/GEJ/E adenocarcinoma, received 1600 mg of domvanalimab intravenously (IV) every four weeks (Q4W) plus 480 mg of zimberelimab IV Q4W + FOLFOX (oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, fluorouracil 400 mg/m2 IV bolus + 2400 mg/m2 continuous 46-48-hour IV infusion) every two weeks.

About Domvanalimab

Domvanalimab is the first and most clinically advanced Fc-silent investigational monoclonal antibody that is specifically designed with Fc-silent properties to block and bind to the T-cell immunoreceptor with Ig and ITIM domains (TIGIT), a checkpoint receptor on immune cells that acts as a brake on the anticancer immune response. By binding to TIGIT with Fc-silent properties, domvanalimab is believed to work by freeing up immune-activating pathways and activate immune cells to attack and kill cancer cells without depleting the peripheral regulatory T cells important in avoiding immune-related toxicity.

Combined inhibition of both TIGIT and programmed cell death protein-1 (PD-1) is believed to significantly enhance immune cell activation, as these checkpoint receptors play distinct, complementary roles in anti-tumor activity. Domvanalimab is being evaluated in combination with anti-PD-1 monoclonal antibodies, including zimberelimab, as well as other investigational cancer immunotherapies and A2a/A2b adenosine receptor antagonist etrumadenant, in multiple ongoing and planned early and late-stage clinical studies in various tumor types.

About Zimberelimab

Zimberelimab is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody that binds PD-1, with the goal of restoring the antitumor activity of T cells. Zimberelimab has demonstrated high affinity, selectivity and potency in various tumor types.

Zimberelimab is being evaluated in the U.S. and globally as a foundational anti-PD-1 treatment option in multiple ongoing and planned early and late-stage clinical studies in combination with other immunotherapies, including investigational Fc-silent anti-TIGIT monoclonal antibody domvanalimab and A2a/A2b adenosine receptor antagonist etrumadenant.

Guangzhou Gloria Biosciences Co. Ltd., which holds commercialization rights for zimberelimab in greater China, has obtained approval for zimberelimab for the treatment of recurrent or metastatic cervical cancer and for relapsed or refractory classical Hodgkin’s lymphoma. Zimberelimab is not approved for any use in the U.S. or other regions outside of China. Gloria conducts its development and commercialization activities independent of Arcus and Gilead.

On June 2, 2024 Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) reported new data from Cohort B of ARC-9, a Phase 1b/2 study evaluating the safety and efficacy of etrumadenant, a dual A2a/b adenosine receptor antagonist, plus anti-PD-1 monoclonal antibody zimberelimab, FOLFOX chemotherapy and bevacizumab (EZFB) in third-line metastatic colorectal cancer (mCRC) (Press release, Gilead Sciences, JUN 2, 2024, View Source [SID1234643935]). These results will be presented today during an oral session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting by Zev A. Wainberg, M.D., MSc, Co-Director of the GI Oncology Program at University of California Los Angeles and a principal investigator of the ARC-9 trial (Abstract 3508).

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"ARC-9 is the first randomized Phase 2 study to show that combining an adenosine receptor blocker with anti-PD-1, anti-VEGF and chemotherapy can meaningfully improve clinical outcomes for people with metastatic colorectal cancer who have progressed on at least two prior therapies," said Dr. Wainberg. "19.7 months is the longest median overall survival reported in third-line mCRC and warrants further investigation of an etrumadenant-based regimen as a potential treatment option in CRC1."

Cohort B of ARC-9 randomized 112 patients with comparable baseline characteristics between two arms: EZFB or regorafenib. At the time of data cut-off (November 13, 2023) median follow-up was 20.4 months. Patient baseline characteristics were similar to those of third-line patients who have progressed on oxaliplatin- and irinotecan-based regimens in mCRC1. OS and PFS were consistently longer in the EZFB arm versus regorafenib, in all sub-groups analyzed, including in patients with liver metastases.

Summary of efficacy results:

EZFB*

n=75

regorafenib

n=37

Median OS, months

19.7

9.5

Hazard Ratio (95% CI), P-value

HR 0.37

95% CI 0.22-0.63

p=0.0003

Median PFS, months

6.2

2.1

Hazard Ratio (95% CI), P-value

HR 0.27

95% CI 0.17-0.43

p<0.0001

Confirmed ORR

13 (17.3%)

1 (2.7%)

Median DOR, months

11.5

NE

CI: confidence interval

OS: overall survival

PFS: progression-free survival

ORR: objective response rate

DOR: duration of response

NE: not evaluable; only one patient with response

*bevacizumab was included for all patients in whom it is not contraindicated

The EZFB regimen had a safety profile consistent with the known safety profiles of each individual molecule to date, without unexpected toxicities. A higher percentage of patients treated with regorafenib (17%) had a treatment emergent adverse event (TEAE) leading to discontinuation of all study drugs than those treated with EZFB (5%). A lower percentage of patients experienced Grade ≥3 TEAEs attributed to etrumadenant or zimberelimab versus regorafenib (23.0% vs 25.7%).

Etrumadenant and zimberelimab are investigational molecules. Neither Gilead nor Arcus has received approval from any regulatory authority for any use of these molecules, and their safety and efficacy for the treatment of colorectal cancer have not been established.

About the ARC-9 Study

ARC-9 (NCT04660812) is a Phase 1b/2 trial evaluating the safety and efficacy of etrumadenant (E), a dual A2a/A2b adenosine receptor antagonist, plus anti-PD-1 antibody zimberelimab (Z), FOLFOX and bevacizumab (if not contraindicated) in three cohorts of patients with mCRC. The primary endpoint is PFS per RECIST 1.1, and OS is a key secondary endpoint. Cohort B enrolled patients who previously progressed on both oxaliplatin- and irinotecan-containing chemotherapy in combination with anti-VEGF (R) therapy or anti-EGFR. Patients were randomized 2:1 to the etrumadenant plus zimberelimab regimen: E (150 mg orally [PO] once daily [QD]) + Z (240 mg intravenous [IV] once every 2 weeks [Q2W]) + mFOLFOX-6 + bevacizumab (5 mg/kg IV Q2W), or regorafenib (administered at a starting dose of 80 mg/day for the first week, followed by a dose escalation of 40 mg every week to 120 mg/day for the second week and 160 mg/day for the third week during Cycle 1 followed by 160 mg/day on Days 1-21 of each subsequent 28-day cycle). Patients who progressed on regorafenib were allowed to crossover to the etrumadenant plus zimberelimab regimen.

ARC-9 is a multi-cohort study in mCRC including Cohort A, which enrolled patients who previously progressed on FOLFOX/FOLFIRI in combination with anti-VEGF(R) or anti-EGFR. Patients were randomized 2:1 to the etrumadenant plus zimberelimab regimen, or FOLFOX-6 + bevacizumab. Data from Cohort A will be presented when they are mature.

About Etrumadenant

Etrumadenant is an investigational small molecule, selective dual antagonist of the A2a and A2b receptors designed to prevent adenosine-mediated immunosuppression. Adenosine elicits its immunosuppressive effects within the tumor microenvironment by binding and activating adenosine-specific receptors expressed on the surface of tumor-infiltrating immune cells, which can help cancer cells evade host antitumor immunity. Once etrumadenant binds to the A2a and A2b receptors and blocks the immunosuppressive effects of adenosine, activation of antitumor immune cells may be restored, which could result in tumor cell death.

Etrumadenant is being evaluated in combination with other cancer immunotherapies, including the investigational Fc-silent anti-TIGIT monoclonal antibody domvanalimab and anti-PD-1 monoclonal antibody zimberelimab, in certain types of non-small cell lung and colorectal cancers.

About Zimberelimab

Zimberelimab is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody that binds PD-1, with the goal of restoring the antitumor activity of T cells. Zimberelimab has demonstrated high affinity, selectivity and potency in various tumor types.

Zimberelimab is being evaluated in the U.S. and globally as a foundational anti-PD-1 treatment option in multiple ongoing and planned early and late-stage clinical studies in combination with other immunotherapies, including investigational Fc-silent anti-TIGIT monoclonal antibody domvanalimab and A2a/A2b adenosine receptor antagonist etrumadenant.

Guangzhou Gloria Biosciences Co. Ltd., which holds commercialization rights for zimberelimab in greater China, has obtained approval for zimberelimab for the treatment of recurrent or metastatic cervical cancer and for relapsed or refractory classical Hodgkin’s lymphoma. Zimberelimab is not approved for any use in the U.S. or other regions outside of China. Gloria conducts its development and commercialization activities independent of Arcus and Gilead.

On June 2, 2024 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported updated interim clinical data on MCLA-145 monotherapy and in combination with pembrolizumab were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place in Chicago May 31-June 4, 2024 (Press release, Merus, JUN 2, 2024, View Source [SID1234643934]).

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"MCLA-145 as monotherapy or with pembrolizumab appears to have a manageable safety profile and early clinical activity in these difficult to treat cancers. Our biomarker data suggest that both dose and less frequent administration may be important determinants of clinical activity, and we are encouraged by the progress we are making with MCLA-145," said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. "As our company is now increasingly focused on our lead asset petosemtamab and plan to initiate phase 3 trials in head and neck cancer later this year, we aim to advance clinical development of MCLA-145 in the context of a potential collaboration."

MCLA-145 (CD137 x PD-L1 Biclonics): Solid Tumors
Interim data included in the presentation describe data from patients (pts) with advanced/metastatic solid tumors who received MCLA-145 Q2W in 28 day cycles or every three weeks (Q3W) in 21 day cycles. Pts treated with the combination of MCLA-145 and pembrolizumab had cancers that either relapsed after PD-(L)1 therapies or were immunotherapy (IO) naïve.

Rapid oral presentation title: Phase I study of MCLA-145, a bispecific antibody targeting CD137 and PD-L1, in solid tumors, as monotherapy or in combination with pembrolizumab
Observations in the presentation include:

As of a January 3, 2024 data cutoff date, 72 pts with multiple cancer types were treated; 25% of pts had non-small cell lung cancer (NSCLC)
All patients were heavily pre-treated with a median of 3 prior therapies; prior IO in 49% of the monotherapy pts and 100% of the combination pts
In monotherapy, 52 pts with a variety of tumor types and treated at different dose levels were evaluable for response
5 partial responses (PRs) were observed at different dose levels in glioblastoma (ongoing as of the cutoff date for >3 years), sarcoma (pretreated with pazopanib and gemcitabine/docetaxel), cervical, anal, and gastric cancer by Response Evaluation Criteria in Solid Tumors v1.1. per investigator assessment
2 of 6 pts PRs (33%) were observed for pts treated at the recommended dose for expansion (RDE), 40 mg Q3W
3 of 6 PRs (50%) were observed for pts with evaluable baseline tumor CD8 T-cell density of ≥ 250 cells/mm2 responded
In combination with pembrolizumab, 19 pts with a variety of tumor types and treated at different dose levels were evaluable for response
1 PR in Merkel cell carcinoma was observed at 25 mg Q3W
1 complete response was observed in PD-L1+ NSCLC at the RDE 40 mg Q3W
3 pts were continuing combination therapy at cutoff date
MCLA-145 monotherapy or in combination with pembrolizumab had a well-tolerated and manageable safety profile at the RDE, 40mg Q3W
Shifting from Q2W to Q3W resulted in a 50% reduction of Grade (G) ≥3 treatment-emergent adverse events in both monotherapy and combination therapy
Liver toxicity, a common CD137 related adverse event, was controlled with no G4 events observed at Q3W
The full presentation is available on the Merus website.

On June 2, 2024 Astrazeneca reported positive results from the ADRIATIC Phase III trial showed ​Imfinzi (durvalumab) ​demonstrated statistically significant and clinically meaningful improvements in the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) compared to placebo for patients with limited-stage small cell lung cancer (LS-SCLC) who had not progressed following standard-of-care concurrent chemoradiotherapy (cCRT) (Press release, AstraZeneca, JUN 2, 2024, View Source [SID1234643933]).

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These results will be presented today during the Plenary Session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (abstract #LBA5).

Results from the planned interim analysis showed Imfinzi reduced the risk of death by 27% versus placebo (based on an OS hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.57-0.93; p=0.0104). Estimated median OS was 55.9 months for Imfinzi versus 33.4 months for placebo. An estimated 57% of patients treated with Imfinzi were alive at three years compared to 48% on placebo. Imfinzi also reduced the risk of disease progression or death by 24% (based on a PFS HR of 0.76; 95% CI 0.61-0.95; p=0.0161) versus placebo. Median PFS was 16.6 months for Imfinzi versus 9.2 months for placebo. An estimated 46% of patients treated with Imfinzi had not experienced disease progression at two years compared to 34% on placebo.

The OS and PFS benefits observed were generally consistent across key prespecified patient subgroups including age, sex, race, disease stage1 at diagnosis, prior radiation and whether patients received prophylactic cranial irradiation.

David R. Spigel, MD, Chief Scientific Officer at Sarah Cannon Research Institute and investigator in the trial, said: "The ADRIATIC results represent a breakthrough in limited-stage small cell lung cancer, a highly aggressive disease where recurrence rates are high and only 15 to 30 per cent of patients survive five years. Durvalumab is the first systemic treatment to show improved survival for these patients in decades and should become a new standard of care in this setting."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "The strong improvement in overall survival seen with Imfinzi after concurrent chemoradiotherapy is transformative in the treatment of limited-stage small cell lung cancer. These tremendous results underscore our ambition to drive up survival rates in this earlier-stage lung cancer setting, and we look forward to working with regulatory authorities to bring Imfinzi to these patients as quickly as possible."

Summary of results: ADRIATIC

​

​Imfinzi

​(n=264)

​Placebo

​(n=266)

OS

Median OS, in months (95% CI)

55.9

(37.3-NEi)

33.4

(25.5-39.9)

Hazard ratio (95% CI)

0.73 (0.57-0.93)

p-value

0.0104

OS rate at 24 months (%)

68.0

58.5

OS rate at 36 months (%)

56.5

47.6

PFS

Median PFS, in months (95% CI)

16.6

(10.2-28.2)

9.2

(7.4-12.9)

Hazard ratio (95% CI)

0.76 (0.61-0.95)

p-value

0.0161

PFS rate at 18 months (%)

48.8

36.1

PFS rate at 24 months (%)

46.2

34.2

​i Not estimable

The safety profile for Imfinzi was generally manageable and consistent with the known profile of this medicine. No new safety signals were observed. Grade 3 and 4 adverse events due to any cause occurred in 24.4% of patients treated with Imfinzi and 24.2% of patients treated on placebo.

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.2 Lung cancer is broadly split into non-small cell lung cancer and SCLC, with about 15% of cases classified as SCLC, a highly aggressive form of the disease.3-4

LS-SCLC (Stage I-III), which accounts for approximately 30% of SCLC diagnoses, is classified as SCLC that is generally only in one lung or one side of the chest.5-6 LS-SCLC typically recurs and progresses rapidly despite initial response to standard-of-care chemotherapy and radiotherapy.4,7 The prognosis for LS-SCLC is particularly poor, as only 15-30% of patients will be alive five years after diagnosis.8

ADRIATIC
The ADRIATIC trial is a randomised, double-blind, placebo-controlled, multi-centre global Phase III trial evaluating Imfinzi monotherapy and Imfinzi plus Imjudo (tremelimumab) versus placebo in the treatment of 730 patients with LS-SCLC who had not progressed following cCRT. In the experimental arms, patients were randomised 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 were 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 included 164 centres in 19 countries across North and South America, Europe and Asia.

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 currently approved in a number of countries across multiple types of lung cancer. Imfinzi is 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 chemoradiation therapy. Imfinzi is also approved for the treatment of extensive-stage SCLC and in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC.

In addition to its indications in lung cancers, Imfinzi is approved in a number of countries in combination with chemotherapy (gemcitabine plus cisplatin) 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 programme, 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 tumours.