On October 22, 2023 Jacobio Pharma (1167.HK), a clinical-stage oncology company focusing on undruggable targets, reported that the clinical data of glecirasib in combination with JAB-3312 was published in the form of a proffered paper presentation at the 2023 European Society for Medical Oncology Congress (ESMO 2023) (Press release, Jacobio Pharmaceuticals, OCT 22, 2023, View Source [SID1234636224]).

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Jacobio presented results of a Phase I/IIa study of glecirasib in combination with JAB-3312. The trial consisted of seven dose groups, including glecirasib of 400 mg and 800 mg in combination with JAB-3312 at different doses and dosing intervals, aiming to explore the safety, efficacy, and tolerability through different dose groups, and to provide a basis for a subsequent registrational clinical trial. As of August 4, 2023, a total of 144 KRAS G12C mutant patients were enrolled, including 129 NSCLC patients, 14 patients with colorectal cancer, and 1 patient with pancreatic cancer.

Among the 129 NSCLC (non-small cell lung cancer) patients involved in the trial, 107 patients had undergone at least one tumor assessment using RECIST1.1 criteria, and 58 of them were first-line therapy patients (spread across the seven dose groups), with an ORR of 65.5% (38/58) and a DCR of 100%. The ORR was 86.7% (13/15) in the dose group[1] of 800 mg glecirasib in combination with 2 mg JAB-3312. The mPFS (median progression-free survival) and duration of response are still under observation as the patients are still undergoing treatment.

The incidence of grades 3 and 4 TRAEs (treatment-related adverse events) was 39.6% across all the dose groups, whereas the incidence of grades 3 and 4 TRAEs was 36.7% in the dose group [1] of 800 mg glecirasib in combination with 2 mg JAB-3312.

Relevant studies have shown that the SHP2 inhibitor is one of the most promising drug partners for the KRAS G12C inhibitor in NSCLC.

"In KRAS G12C mutant NSCLC patients, the combination therapy of glecirasib with JAB-3312 has shown positive efficacy signals. Compared with monotherapy, combination therapy can synergistically inhibit tumor growth. In addition, both drugs are administered orally, so patients do not need to be hospitalized, which is more convenient for patients," said Prof. Jie WANG from the Cancer Hospital, Chinese Academy of Medical Sciences, the principal investigator of this trial. "We look forward to further validating the clinical efficacy of the combination therapy through follow-up studies."

"The data provides the basis for the registrational clinical study of glecirasib in combination with SHP2 inhibitor. The research team will determine the following registrational clinical trial plan based on the optimal dose combination of this trial after the PFS data matures," said Andrea WANG-GILLAM M.D., Ph.D., Chief Medical Officer of Jacobio. "SHP2 is a target for which there are no approved or marketed inhibitors anywhere in the world. We hope that through this study, we can bring confidence to SHP2 inhibitor investigators, improve the response rate of the KRAS G12C inhibitor as monotherapy, prolong patients’ survival periods, and improve their quality of life."

[1] Once daily for 1 week on, then 1 week off.

For more information, please visit the official website of ESMO (Free ESMO Whitepaper): View Source

Conference Call Information
Jacobio will host a live conference call on Oct. 24, 2023, at 14:00-15:00 (UTC+8). Participants must register in advance of the conference call. Registration Link: View Source

About Glecirasib
Glecirasib is a KRAS G12C inhibitor developed by Jacobio. A number of Phase I/II clinical trials of glecirasib are currently ongoing in China, the United States and Europe for patients with advanced solid tumors harboring KRAS G12C mutation. These include a pivotal clinical trial in NSCLC in China; a monotherapy study for STK11 co-mutated NSCLC in the front-line setting, and combination therapy trials with SHP2 inhibitor JAB-3312 in NSCLC and with Cetuximab in colorectal cancer.

About JAB-3312
JAB-3312 is a highly selective SHP2 allosteric inhibitor with best-in-class potential. Jacobio is currently conducting clinical trials of JAB-3312 in monotherapy and combination therapies with glecirasib and other agents in China, the United States and Europe.

On October 22, 2023 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the first results from an open-label, multicenter Phase 1 study evaluating the safety and efficacy of TAR-210, an intravesical delivery system designed to provide sustained, local release of erdafitinib into the bladder in patients with non-muscle-invasive bladder cancer (NMIBC) with select fibroblast growth factor receptor (FGFR) alterations (Press release, Johnson & Johnson, OCT 22, 2023, View Source [SID1234636223]). These data were featured today in a Late-Breaking Mini-Oral Presentation Session (Abstract #LBA104) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2023 Congress taking place October 20-24 in Madrid, Spain.1

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Results featured data from Cohort 1 [(C1); patients with recurrent, Bacillus Calmette-Guérin (BCG)-unresponsive high-risk (HR) NMIBC (high-grade Ta/T1; papillary only) who refused or were ineligible for radical cystectomy] and Cohort 3 [(C3); patients with intermediate-risk (IR) NMIBC (Ta/T1) low-grade papillary disease] left in situ as tumor marker lesions.

At the data cutoff of 29 August 2023, 43 patients had been treated with TAR-210 across the two cohorts. Of the 16 patients in C1 with HR NMIBC having at least one response assessment, 82 percent were recurrence-free (RF). Median duration of treatment exposure was 3.7 months, with 94 percent of the 16 patients still on study. In C3, 87 percent of the 27 patients having at least one response assessment with IR NMIBC achieved a complete response (CR). Median duration of treatment exposure was 4.2 months.

The most common treatment-related adverse events (TRAEs) were Grade 1/2 lower urinary tract TRAEs. There were no dose-limiting toxicities and no deaths. Two patients discontinued the study due to TRAEs of low-grade urinary symptoms and one patient had serious TRAEs of pyelonephritis and sepsis.

"Patients with high- or intermediate-risk non-muscle-invasive bladder cancer have seen limited advancement in the treatment landscape over the last 50 years and the available options are associated with a high risk of recurrence and significant side effect burden," said Antoni Vilaseca,* M.D., Ph.D. of the Hospital Clínic de Barcelona and presenting author of the Phase 1 TAR-210 study. "We look forward to further results from this study in the future and the ongoing development of the localized delivery of erdafitinib."

"We are advancing this novel technology with the ambition of bringing bladder-sparing and BCG-free regimens to patients with localized bladder cancer," said Jeffrey Infante, M.D., Global Head, Oncology Early Clinical Development and Translational Research, Janssen Research & Development, LLC. "These encouraging results reinforce our commitment to improving patient outcomes by treating early-stage disease with this intravesical delivery technology."

About TAR-210
TAR-210 is an investigational erdafitinib intravesical delivery system. The safety and efficacy of TAR-210 is being evaluated in a Phase 1 study (NCT05316155) in patients with muscle-invasive bladder cancer (MIBC) and NMIBC. The study categorizes patients into four cohorts based on their disease presentation. Cohort 1 (C1) includes patients with recurrent, BCG-unresponsive high-risk NMIBC with concomitant high-grade papillary disease who have refused or are ineligible for radical cystectomy (RC). Cohort 2 (C2) includes patients with the same presentation, but who are scheduled for RC. Cohort 3 (C3) includes patients with recurrent, intermediate-risk NMIBC with a history of low-grade papillary disease. To be eligible for C3, the presence of visible tumor(s) is required. Cohort 4 (C4) includes patients with muscle-invasive bladder cancer. The primary endpoint of the study is safety (adverse events, including dose-limiting toxicity). Secondary endpoints include pharmacokinetics (PK), RF survival in patients in C1 and C2, CR rate and duration of CR in patients in C3 and pathologic CR rate in C4.2

About Non-Muscle-Invasive Bladder Cancer
Non-muscle-invasive bladder cancer (NMIBC) is cancer found in the tissue that lines the inner surface of the bladder. The bladder muscle is not involved. Patients are categorized into one of three risk groups which describe how likely the cancer is to progress, spread further, or come back after treatment: low-risk, intermediate-risk or high-risk. Radical cystectomy is currently recommended for NMIBC patients who fail Bacillus Calmette-Guérin (BCG) therapy, with over 90 percent cancer-specific survival if performed before muscle-invasive progression.3,4 Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo radical cystectomy.5 The high rates of recurrence and progression can pose significant morbidity and distress for these patients.

On October 22, 2023 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that data from the Phase 2b SunRISe-1 study evaluating the efficacy and safety of TAR-200 monotherapy in patients with Bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non-muscle-invasive bladder cancer (HR-NMIBC), who are ineligible for, or decline, radical cystectomy, showed that 77 percent of patients (23 out of 30 [95 percent Confidence Interval (CI), 58-90]) achieved a complete response (CR) (Press release, Johnson & Johnson, OCT 22, 2023, https://www.prnewswire.com/news-releases/tar-200-intravesical-delivery-system-results-show-77-percent-complete-response-rate-in-patients-with-bacillus-calmette-guerin-unresponsive-high-risk-non-muscle-invasive-bladder-cancer-301963786.html [SID1234636222]). These data were featured today in a Late-Breaking Mini-Oral Presentation Session (Abstract #LBA105) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2023 Congress taking place October 20-24 in Madrid, Spain.1

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TAR-200 is an investigational intravesical drug delivery system designed to provide sustained local release of gemcitabine into the bladder. Interim results from the SunRISe-1 study were featured earlier this year at the American Urological Association Annual Meeting. Results presented today included an evaluation of 54 patients (median age of 71; range 40-85; 33 percent with concurrent papillary disease) who received TAR-200 monotherapy. Centrally confirmed CR by urine cytology and/or biopsy was achieved in 23 of 30 patients (CR 77 percent; 95 percent CI, 58-90) and investigator-confirmed CR was achieved in 24 out of 30 patients (CR 80 percent; 95 percent CI, 61-92). Twenty-one out of 23 responders had ongoing CR with 11 patients maintaining their CR for six months or more, and six patients had ongoing CR for 12 months or more. Median duration of response (DOR) was not reached.

Treatment-related adverse events (TRAEs) occurred in 29 patients (54 percent). The most common (≥10 percent) were pollakiuria, dysuria, micturition urgency, and hematuria. Four patients (seven percent) had Grade 3 or higher TRAEs and one patient (two percent) had serious TRAEs. Two patients (four percent) had TRAEs leading to discontinuation and no deaths were reported.

"Patients with NMIBC, who are unresponsive to BCG treatments, are at high risk for disease progression, and unfortunately, available treatment options remain limited," said Andrea Necchi,* M.D., of Italy’s Vita-Salute San Raffaele University and the IRCCS San Raffaele Hospital and Scientific Institute and a presenting author of the study. "The results of TAR-200 observed in this study present a potential less-invasive option for patients in the future."

"The current treatment options for patients with HR-NMIBC, who are unresponsive to BCG, remain limited and typically include repeated BCG therapy or radical cystectomy," said Christopher Cutie, M.D., Vice President, Disease Area Leader, Bladder Cancer, Janssen Research & Development, LLC. "Our goal is to transform the treatment landscape for patients with bladder cancer through innovative approaches that focus on bladder preservation and long-term survival."

Bladder cancer is the tenth most common cancer worldwide, with more than 600,000 patients diagnosed each year, and more than 200,000 new cases every year across Europe alone.2

About SunRISe-1
SunRISe-1 (NCT04640623) is a randomized, parallel-assignment, open-label Phase 2 clinical study evaluating the safety and efficacy of TAR-200 in combination with cetrelimab, TAR-200 alone, or cetrelimab alone for BCG-unresponsive HR-NMIBC carcinoma in situ (CIS) patients who are ineligible for, or decline, radical cystectomy. Participants are randomized to one of three cohorts: treatment with TAR-200 in combination with cetrelimab (Cohort 1), TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3). The primary endpoint is CR rate at any time point. Secondary endpoints include DOR, overall survival, pharmacokinetics, quality of life, safety, and tolerability. Cohorts 1 and 3 were closed to further enrollment effective June 1, 2023.

About TAR-200
TAR-200 is an investigational drug delivery system, enabling controlled release of gemcitabine into the bladder, increasing the amount of time the drug delivery system spends in the bladder and sustaining local drug exposure. The safety and efficacy of TAR-200 are being evaluated in Phase 2 and Phase 3 studies in patients with muscle-invasive bladder cancer in SunRISe-2 and SunRISe-4 and NMIBC in SunRISe-1 and SunRISe-3.

About Cetrelimab
Administered intravenously, cetrelimab is an investigational programmed cell death receptor-1 (PD-1) monoclonal antibody being studied for the treatment of bladder cancer, prostate cancer, melanoma, and multiple myeloma as part of a combination treatment. Cetrelimab is also being evaluated in multiple other combination regimens across the Janssen Oncology portfolio.

About High-Risk Non-Muscle-Invasive Bladder Cancer
High-risk non-muscle-invasive bladder cancer (HR-NMIBC) is a type of non-invasive bladder cancer that is more likely to recur or spread beyond the lining of the bladder, called the urothelium, and progress to invasive bladder cancer compared to low-risk NMIBC. 3, 4 HR-NMIBC makes up 15–44 percent of patients with NMIBC and is characterized by a high-grade, large tumor size, presence of multiple tumors, and CIS. Radical cystectomy is currently recommended for NMIBC patients who fail BCG therapy, with over 90 percent cancer-specific survival if performed before muscle-invasive progression.5,6 Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo radical cystectomy.7 The high rates of recurrence and progression can pose significant morbidity and distress for these patients.

On October 22, 2023 InxMed Co., Ltd, a clinical-stage biotechnology company dedicated on developing innovative therapies to overcome drug resistance for hard-to-treat solid tumors, reported that clinical data of Ifebemtinib (IN10018), a highly potent and selective oral inhibitor of focal adhesion kinase (FAK), in platinum-resistant recurrent ovarian cancer (PROC) and triple-negative breast cancer (TNBC) has been presented at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress taking place October 20-24 in Madrid, Spain (Press release, InxMed, OCT 22, 2023, View Source [SID1234636221]). Both of the two studies showed that patients receiving IN10018 containing regimens demonstrated promising antitumor activities with trends toward survival benefit.

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Platinum-Resistant Recurrent Ovarian Cancer（Poster #：753P）

In a single-arm, open-label, phase Ib trial, PROC patients received IN10018 in combination with pegylated liposomal doxorubicin (PLD) treatment.

The combination of IN10018 with PLD showed prolonged survival in PROC patients and manageable safety profile. As of cutoff date of April 28, 2023, a total of 61 patients were enrolled with median follow-up duration of 14.0 months. Comparing with historical data by PLD alone with an ORR (Objective Response Rate) of ~10%, median PFS (Progression-Free Survival) of 3.3 months and median OS (Overall Survival) of 12 months, the ORR of PLD in combination with IN10018 was 46.3% (95% CI：32.6-60.4), the DCR (Disease Control Rate) was 83.3% (95% CI 70.7-92.1), the median PFS was 7.56 months (95% CI: 5.5 – 9.1 months), the median OS was 20.9 months (95% CI: 14.4 months – NA) and still maturing. The safety profile of the combination is comparable to these single agents alone without additive toxicities.

Triple-Negative Breast Cancer (Poster#：398P)

This phase Ib/II study was to evaluate the safety, tolerability, and antitumor activity of IN10018 combined with PLD with/without anti-PD-1 antibody Toripalimab in previously-treated solid tumors with metastatic TNBC who had failed in 1-2 lines of systemic therapy.

As of the cutoff date of August 31, 2023, 12 patients received IN10018 + PLD (doublet) and 14 patients received IN10018 + PLD + Toripalimab (triplet). Historical data showed a median PFS was 4.3 months when PLD and low dose of cyclophosphamide is combined with anti-PD-1. In doublet group, the median PFS was 3.65 months (95% CI：1.77-7.29), and median OS was 8.26 months (95% CI, 5.59-NA). In triplet group, the median PFS was 7.43 months (95% CI：3.02-10.8), and median OS was not reached with the low boundary of 95% CI as 9.26 months. The safety profiles of both doublet group and triplet group in metastatic TNBC are tolerable and comparable to each single agent alone.

FAK signaling has been shown to be critical in pathologic fibrosis and is hyperactivated in many cancer types. FAK activation is correlated with poor survival and treatment resistance of tumors.

InxMed is developing IN10018 globally. IN10018 has received fast track designation from the U.S. Food and Drug Administration (FDA) and breakthrough designation from China National Medical Products Administration (NMPA).

A placebo-controlled, randomized, double-blind Phase II pivotal trial is ongoing to confirm the observed efficacy and safety of IN10018 in PROC. New Drug Application (NDA) is expected to be submitted in 2024.

On October 22, 2023 Astrazeneca reported updated results from the BEGONIA Phase Ib/II trial for the cohort of patients treated with datopotamab deruxtecan (Dato-DXd) plus Imfinzi (durvalumab) (Arm 7) showed that the combination demonstrated durable tumour responses and no new safety signals in patients with previously untreated advanced or metastatic triple-negative breast cancer (TNBC) with six months additional follow-up from the previous data cut-off (Press release, AstraZeneca, OCT 22, 2023, View Source [SID1234636219]).

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These data will be presented today in a mini oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2023 Congress in Madrid, Spain (379MO).

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

Approximately 300,000 people worldwide are diagnosed annually with TNBC, the most aggressive breast cancer subtype.1-2 Less than half of patients with metastatic TNBC respond to current 1st-line treatment options which can include chemotherapy alone or in combination with an immunotherapy.2-4 Among patients with tumours that do respond to initial treatment, disease progression is common and rapid, often occurring within two years.2,4-6

Results showed that datopotamab deruxtecan plus Imfinzi, an anti-PD-L1 therapy, demonstrated a confirmed objective response rate (ORR) of 79% (n=49 of 62) including six complete responses (CRs) and 43 partial responses (PRs). Responses were observed regardless of PD-L1 expression level. Median progression-free survival (PFS) was 13.8 months (95% confidence interval [CI] 11-not calculable [NC]) and median duration of response (DoR) was 15.5 months (95% CI: 9.9-NC) with 11.7 months of follow-up.

Peter Schmid, MD, Barts Cancer Institute, London, United Kingdom, and investigator in the trial, said: "These results for datopotamab deruxtecan plus durvalumab in the first-line triple-negative breast cancer setting are highly encouraging, particularly the 79% objective response rate. This magnitude of response is especially notable given the majority of patients in this cohort have PD-L1-low tumours, representing a population for whom treatment has long been limited to standard chemotherapy."

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: "Progress in the first-line advanced triple-negative breast cancer setting has been modest for years and new therapeutic strategies are needed to improve outcomes for patients with this aggressive breast cancer subtype. These updated results from the BEGONIA trial reinforce our confidence in the potential for datopotamab deruxtecan to become a new, important treatment modality in this setting as we eagerly await results from our ongoing Phase III triple-negative breast cancer programme."

Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo, said: "Disease progression after initial treatment is a reality for patients with triple-negative breast cancer, underscoring the need for more durable treatment options. These findings showcase the potential of datopotamab deruxtecan in previously untreated advanced triple-negative breast cancer and, following the positive results of our TROPION-Breast01 Phase III trial, build on the growing body of evidence for the potential use of this TROP2-directed antibody drug conjugate, alone and in combinations, in several subtypes of breast cancer."

The safety profile of datopotamab deruxtecan in combination with Imfinzi was consistent with the known safety profiles of both agents. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 57% of patients. The most common Grade 3 or higher TEAEs were increased amylase (18%), stomatitis (11%), constipation (2%), fatigue (2%), vomiting (2%) and decreased appetite (2%). There were three interstitial lung disease (ILD) events adjudicated as drug-related by an independent committee including two Grade 2 events and one Grade 1 event.

In Arm 7 of the BEGONIA trial (n=62), the majority of patients (n=54) had tumours with low PD-L1 expression (tumour area positivity [TAP] <10%). Seven patients had tumours with high PD-L1 expression (TAP ≥10%). As of the 2 February 2023 data cut-off, 29 patients (47%) remained on study treatment.

Summary of BEGONIA Arm 7 Efficacy Results

Efficacy Measure (as assessed by investigator)

All Patients (n=62)

ORR, confirmed (95% CI)

79% (n=49) (66.8-88.3)

CR rate

10% (n=6)

PR rate

69% (n=43)

Median DoR (95% CI)

15.5 months (9.9-not calculable)

Median PFS (95% CI)

13.8 months (11.0-not calculable)

CR; complete response; CI, confidence interval; DCR, disease control rate; ORR, objective response rate; PR, partial response; PD, progressive disease; SD, stable disease
i ORR is (complete response + partial response)

AstraZeneca and Daiichi Sankyo have two Phase III trials evaluating datopotamab deruxtecan in TNBC. TROPION-Breast02 is comparing datopotamab deruxtecan to chemotherapy in patients with previously untreated locally recurrent inoperable or metastatic TNBC who are not candidates for anti-PD-L1 therapy. TROPION-Breast03 is evaluating datopotamab deruxtecan with and without Imfinzi versus investigator’s choice of therapy in patients with Stage I-III TNBC with residual disease after neoadjuvant therapy.

Several presentations featured during the ESMO (Free ESMO Whitepaper) 2023 Congress are showcasing the strength and depth of data for datopotamab deruxtecan across multiple tumour types and settings, including results from the TROPION-Lung01 and TROPION-Breast01 Phase III trials.

Notes

Triple-negative breast cancer
Breast cancer is the most common cancer in the world and leading cause of cancer-related death.1 More than two million breast cancer cases were diagnosed in 2020 with nearly 685,000 deaths globally.1

While some breast cancers may test positive for oestrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three.2 Approximately 15% of breast cancer tumours (300,000 cases annually) are considered triple-negative which is the most aggressive breast cancer subtype.1-2 1st-line treatment for advanced or metastatic TNBC usually consists of chemotherapy alone or in combination with an immunotherapy – options generally associated with response rates between 30 to 50%.2-4 Among patients with tumours that do respond to initial treatment, disease progression is common and rapid, often occurring within two years.2,4-6 The average overall survival of patients living with advanced or metastatic TNBC is 12 to 18 months, with only about 12% of patients living five years following diagnosis.7-8

TROP2 is a protein broadly expressed in several solid tumours, including TNBC.9 TROP2 is associated with increased tumour progression and poor survival in patients with breast cancer.9-10

BEGONIA
BEGONIA is an open-label, two-part, multicentre Phase Ib/II trial evaluating Imfinzi in combination with oncology therapies with or without paclitaxel for the 1st-line treatment of metastatic TNBC. Arm 7 of the trial is evaluating the safety, tolerability and preliminary efficacy of datopotamab deruxtecan (6.0 mg/kg) in combination with Imfinzi (1120 mg) in patients with previously untreated, unresectable locally advanced or metastatic TNBC. The primary endpoints are safety and tolerability. Secondary endpoints are investigator-assessed ORR, PFS and DOR.

Enrolment is currently underway for Arm 8 of the BEGONIA trial, which is evaluating datopotamab deruxtecan plus Imfinzi in patients with TNBC whose tumours have high levels of PD-L1 expression.

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 six 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 called TROPION is underway globally with more than 12 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple TROP2-targetable tumours, including non-small cell lung cancer (NSCLC), TNBC and HR-positive, HER2-low or 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 small cell lung cancer (SCLC) based on the CASPIAN Phase III trial. 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 indication in lung cancer, Imfinzi is also approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer (BTC) and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC) in the US, EU, Japan and several other countries based on the TOPAZ-1 and HIMALAYA Phase III trials, respectively. Imfinzi is approved 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.

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