On December 8, 2022 Promontory Therapeutics Inc., a clinical stage pharmaceutical company advancing small molecule immunotherapies in oncology, reported Phase 2a clinical safety and efficacy data on lead therapeutic candidate PT-112 in combination with PD-L1 inhibition, in patients with advanced non-small cell lung cancer (NSCLC) at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Congress 2022 (Press release, Promontory Therapeutics, DEC 8, 2022, View Source [SID1234624971]).

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The poster titled, "A phase 2a study of the novel immunogenic cell death (ICD) inducer PT-112 plus avelumab in advanced non-small cell lung cancer patients," demonstrated that the PT-112 and avelumab combination is well-tolerated with manageable safety profile, and showed meaningful clinical benefits in patients without known predictive markers for immunotherapy response. Based on the clinical activity observed, the study’s results support further evaluation of PT-112 combinations with immuno-oncology agents and assessment of PT-112’s immunological effects in patients.

"These data give us proof of principle for the use of immunogenic cell death inducer PT-112 in combination with immune checkpoint inhibition in NSCLC patients, and are supportive of future opportunities to bring our intended immunotherapy combinations to cancer patients," said Matthew Price, Promontory Therapeutics co-founder and Chief Operating Officer. "Along with immune correlative findings, the results are encouraging. As the field of immunogenic small molecules continues to evolve, we are pleased to continue to demonstrate the ICD effects of PT-112 in human patients. Our published clinical and non-clinical studies to date have shown the potential of this approach."

The 18 patients enrolled in the study were treated with 360 mg/m2 of PT-112 on days one, eight, and 15, and 800 mg of avelumab on days one and 15, of a 28-day cycle. Eligible patients received no more than 4 prior lines of therapy and were required to have progressive disease and to have received prior anti-PD-1/PD-L1 and platinum treatment. Findings from the study include:

Common treatment-related adverse events (TRAEs) were anemia (50%), fatigue (50%), thrombocytopenia (44%), nausea (44%) and anorexia (44%).
There were no PT-112 grade 4-5 TRAEs reported.
Of the 15 patients evaluable for efficacy, six patients (40%) had stable disease or better by iRECIST criteria.
Two cases of radiographic and clinical improvement were noted:
One patient achieved unconfirmed partial response at the first imaging follow-up, with documentation of a 70% decrease in target lesions, followed by a complete response in target and non-target lesions along with relief of pulmonary symptoms. Post-progression, PET images showed that the patient’s disease remained well-controlled for an additional ~7 months with no subsequent treatments, suggestive of extended immune-related clinical benefit.
One patient achieved a metabolic FDG-PET response, showed increased T-cell fraction on treatment, and remained stable with a progression-free survival of 7.3 months.
Based on preclinical models, PT-112 is an immunogenic small molecule that induces ICD, recruits immune effector cells in the tumor microenvironment, and synergizes with immune checkpoint inhibitors.

For more information about PT-112 and Promontory Therapeutics’ clinical pipeline visit www.PromontoryTx.com.

About PT-112
PT-112 is the first small-molecule conjugate of pyrophosphate in oncology, and possesses a unique pleiotropic mechanism of action that promotes immunogenic cell death (ICD), through the release of damage associated molecular patterns (DAMPs) that bind to dendritic cells and lead to downstream immune effector cell recruitment in the tumor microenvironment. PT-112 represents a highly potent inducer of this immunological form of cancer cell death. Further, PT-112 harbors a property known as osteotropism, or the propensity of the drug to reach its highest concentrations in certain areas of the bone, making it a candidate for treatment of patients with cancers that originate in, or metastasize to, the bone. The first in-human study of PT-112 demonstrated an attractive safety profile and evidence of long-lasting responses among heavily pre-treated patients and won "Best Poster" within the Developmental Therapeutics category at the ESMO (Free ESMO Whitepaper) 2018 Annual Congress. The combination Phase 1b dose escalation study of PT-112 with PD-L1 checkpoint inhibitor avelumab in solid tumors was reported in an oral presentation at the ESMO (Free ESMO Whitepaper) 2020 Virtual Congress and the Phase 2a dose confirmation cohort in non-small cell lung cancer (NSCLC) patients reported at ESMO (Free ESMO Whitepaper) IO 2022. The Phase 1 study in patients with relapsed or refractory multiple myeloma presented at ASH (Free ASH Whitepaper) is the third completed Phase 1 study of PT-112. Monotherapy Phase 2 development is ongoing in mCRPC, and now includes the Phase 2 proof of concept study in thymic epithelial tumors under the company’s formal collaboration with the NCI.

On December 8, 2022 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, reported preliminary results from its ongoing potentially pivotal trial evaluating Berubicin for the treatment of recurrent glioblastoma multiforme (GBM) (Press release, CNS Pharmaceuticals, DEC 8, 2022, View Source [SID1234624970]).

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"Although data are still early, we are pleased with these results in terms of recruiting a balanced patient population to compare Berubicin to Lomustine in the treatment of GBM, which may highlight Berubicin’s potential to provide a better therapeutic option for patients after first-line therapy for their disease. We remain steadfast in our efforts to drive patient enrollment across the U.S. and Europe and are making significant progress toward our planned interim analysis, which we expect to occur in mid-2023. Our team remains dedicated to moving this important program forward and to providing patients, families and physicians with a much needed treatment opportunity for this devastating disease," commented John Climaco, CEO of CNS Pharmaceuticals.

"Berubicin continues to demonstrate its ability to be an innovative treatment in GBM as a safe and potentially effective therapy. These preliminary findings bolster our conviction in Berubicin as we continue to advance this study forward. Based on the results we’ve seen preclinically and in the clinic thus far, we remain confident in Berubicin’s potential to provide a consequential and much needed clinical benefit for GBM patients. We are making excellent progress with patient recruitment worldwide and, because we have currently described a balanced randomized population, we look forward to providing a meaningful comparison between Berubicin and what has been considered a standard of care for second line therapy (Lomustine)," added Sandra Silberman, MD, PhD, Chief Medical Officer of CNS Pharmaceuticals.

The preliminary results showed that the enrolled patients have comparable demographics, including age, gender, race, BSA and KPS and, in addition, the unmethylated MGMT population, which was approximately 40% in both arms. The percentage of patients that are currently continuing on study or having withdrawn is also comparable between arms. All grades of adverse events occurring in more than 5% of patients, as well as Grade 3-5 events, were also similar in the Berubicin and Lomustine arms.

As of the data cutoff of October 17, 2022, 49 patients were enrolled in this potentially pivotal trial with 35 subjects on Berubicin and 14 subjects on Lomustine, reflective of the Company’s 2:1 randomization schema. This study is evaluating the efficacy of this novel drug in terms of overall survival (OS), with the goal of providing the first approved therapeutic option for patients after first-line therapy. A pre-planned, non-binding futility analysis of OS will be performed after approximately 30 to 50% of all planned patients are enrolled in the study. These patients will be evaluated at 6 months after enrollment in the study, which we expect mid-year 2023. This review will include additional evaluation of safety as well as secondary efficacy endpoints related to the efficacy of Berubicin. Enrollment will not be paused during this interim analysis.

The data were recently presented by Dr. Silberman at the Society of Neuro-Oncology’s 27th Annual Meeting in a poster titled, "A Randomized, Controlled Trial of Berubicin, a Doxorubicin Analog That Effectively Crosses the Blood-Brain Barrier (BBB), After First-Line Therapy for Glioblastoma Multiforme (GBM): Preliminary Results1."

The Company can now report that subsequent to Dr. Silberman’s presentation at the Society of Neuro-Oncology’s 27th Annual Meeting, enrollment has increased to 67 patients in this potentially pivotal study. "It is a remarkable testament to both the design of our study and the magnitude of the unmet clinical need in this terrible disease that our study is enrolling at this rapid pace. We are extremely grateful to our patients, our investigators and to our investors who are all facilitating this potentially game-changing clinical program," said John Climaco, Chairman and CEO of CNS Pharmaceuticals, Inc.

For more information about the ongoing potentially pivotal Berubicin trial, visit clinicaltrials.gov and reference identifier NCT04762069.

About Berubicin

Berubicin is an anthracycline, a class of anticancer agents that are among the most powerful chemotherapy drugs and effective against more types of cancer than any other class of chemotherapeutic agents. Anthracyclines are designed to utilize natural processes to induce deoxyribonucleic acid (DNA) damage in targeted cancer cells by interfering with the action of topoisomerase II, a critical enzyme enabling cell proliferation. Berubicin treatment of brain cancer patients appeared to demonstrate positive responses that include one durable complete response in a Phase 1 human clinical trial conducted by Reata Pharmaceuticals, Inc. Berubicin, was developed by Dr. Waldemar Priebe, Professor of Medicinal Chemistry at The University of Texas MD Anderson Cancer Center. The FDA has granted CNS Pharmaceuticals Fast Track Designation and Orphan Drug Designation for Berubicin.

On December 8, 2022 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, reported that clinical data of IBI939 (anti-TIGIT monoclonal antibody) is presented at the 2022 European Society for Medical Oncology Immuno-Oncology Congress (ESMO-IO), Dec 7-9, 2022 (Press release, Innovent Biologics, DEC 8, 2022, View Source [SID1234624969]).

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A Phase Ib Study to Evaluate the Safety, Tolerability and Efficacy of IBI939 in Combination With Sintilimab in Patients with Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1-Selected NSCLC

Poster #: 77P

IBI939 is a recombinant fully human anti-T-cell immunoreceptor with Ig and ITIM domains (TIGIT) monoclonal antibody developed by Innovent Biologics. This Phase Ib study aimed to evaluate safety, tolerability, and efficacy of combination therapy of IBI939 with sintilimab in patients with previously untreated, locally advanced unresectable or metastatic PD-L1 TPS≥50% NSCLC without sensitizing mutations. As of October 15th, 2022, 42 pts were randomized (2:1) to receive IBI939 plus sintilimab (experimental arm) or sintilimab monotherapy (control arm). The study results were as follows:

Baseline characteristics: in the experimental arm (n=28), median age was 65 and 7 (25%) patients have brain metastasis; in the control arm (n=14), median age was 58 and 1 (7.1%) patient has brain metastasis.
As of the data cutoff date, among 40 efficacy evaluable patients (27 vs. 13). The median follow-up duration was 11.0 mos (95%CI, 9.6-11.3) in experimental arm and 9.8 mos (95%CI, 8.1-10.9) in control arm. Confirmed objective response rate (ORR) was 64.3% vs 57.2% and the disease control rate (DCR) was 85.7% vs 78.6% in experimental arm and control arm, respectively. The median PFS was 11.2 mos (95%CI, 6.7-NA) in experimental arm vs 6.4 mos (95% CI, 1.4-NA) in control arm (HR: 0.55);
For safety results, the incidence of TRAEs was 96.4% vs 71.4% (4 vs 5 pts experienced grade ≥ 3 TRAEs), in experimental arm vs control arm, respectively. Two patients in experimental arm and one patient in control arm experienced TRAE leading to study treatment discontinuation. No grade 5 TRAE happened in experimental arm.
The study is still ongoing; primary efficacy data will be further evaluated and presented in future medical conferences.
Professor Ying Cheng, Jilin Cancer Hospital, stated: "PD-L1 TPS≥50% NSCLC is sensitive to PD-1/PD-L1 inhibitors as first-line systemic therapy indicating promising survival benefits for patients[1]. IBI939 plus sintilimab bring encouraging efficacy to patients and present a manageable safety profile in the Phase Ib study. The study is still ongoing, and we look forward to the follow-up results of positive efficacy data in the future."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to present the clinical development updates of IBI939 at the 2022 ESMO (Free ESMO Whitepaper)-IO Meeting. IBI939, in combination with sintilimab, demonstrated encouraging efficacy and safety data in the Phase Ib clinical study. PFS benefit and tolerable safety profiles were observed. We will continue to provide updates on the PoC data readout for IBI939 in treatment areas such as lung cancer and plan to initiate subsequent pivotal clinical studies. As immunotherapy moves into the next era, we continue to focus on developing and commercializing high-quality biopharmaceuticals that are affordable to ordinary people."

To learn more about Innovent’s R&D updates and activities, please visit View Source

About IBI939

IBI939 is an IgG4κ recombinant human anti-TIGIT monoclonal antibody developed by Innovent Biologics. Targeting TIGIT on T cells and NK cell membranes in the tumor microenvironment, this drug candidate can prevent the binding of CD155 overexpressed on the cancer cell membrane to TIGIT, thereby restoring the activation of cytotoxic T cells and NK cells, and exerting tumor killing effects[2]. TIGIT and PD-1 are both immunosuppressive checkpoint receptors. Inhibition of TIGIT and PD-1 can synergistically promote immune cells to kill tumors and enhance anti-tumor immune response.

On December 8, 2022 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, reported that updated clinical data of IBI110 (anti-LAG-3 monoclonal antibody) in advanced squamous non-small cell lung cancer (sqNSCLC) is presented at the 2022 European Society for Medical Oncology Immuno-Oncology Congress (ESMO-IO), held Dec 7-9, 2022 (Press release, Innovent Biologics, DEC 8, 2022, View Source [SID1234624967]).

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Efficacy and safety of IBI110 (anti-LAG-3 mAb) in combination with Sintilimab (anti-PD-1 mAb) in Advanced Squamous Non-small Cell Lung Cancer (sqNSCLC): Updated Results from a Phase Ib Study

Poster #: 86P

IBI110 is an IgG4κ recombinant human anti-LAG-3 monoclonal antibody developed by Innovent Biologics. The Phase Ib study aims to evaluate the efficacy and safety of IBI110 in combination with sintilimab and chemotherapy (paclitaxel plus carboplatin) as first-line therapy for advanced sqNSCLC.

20 treatment naïve sqNSCLC patients received IBI110 (200 mg, Q3W) combined with sintilimab and chemotherapy and received at least 1 post-baseline tumor assessment. As of the data cutoff date of Oct 25, 2022, median follow-up time was 12.0 (95% CI, 11.9 -13.1) months, 16 patients achieved partial response (PR), the objective response rate (ORR) was 80%; the 12-month progression free survival (PFS) rate was 60.0% (95% CI, 35.7-77.6), the median PFS was not reached; the 12-month overall survival (OS) rate was 85.0% (95% CI, 60.4-94.9) .
For safety results, the most common treatment related adverse events (TRAEs) ≥ grade 3 were decreased neutrophil count (30.0%) and decreased white blood cell count (20.0%). Immune-related AEs (irAEs) occurred in 14 patients, in which only 4 patients experienced irAE ≥ grade 3. No treatment-related deaths occurred.
IBI110 combined with sintilimab and chemotherapy in advanced sqNSCLC continues to show robust anti-tumor activity and favorable safety. The study is ongoing with the clinical data in squamous NSCLC continuing to mature and will be disclosed in the future academic conference/journals.
Professor Caicun Zhou, Shanghai Pulmonary Hospital, stated: "Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide, of which non-small cell lung cancer accounts for about 80%1. In recent years, PD-1/PD-L1 inhibitors have shown promising efficacy in non-small cell lung cancer2. However, persistent response to immune checkpoint inhibitor monotherapy remains a challenge in clinical practice. IBI110 plus sintilimab indicate promising antitumor activity and a manageable safety profile in untreated squamous non-small cell lung cancer patients. In the current 20 patients, the ORR reached 80% and the 12-month PFS rate was 60%, which warrants further investigation into the safety and efficacy of IBI110 combination therapy in this indication."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to present our clinical development updates at the 2022 ESMO (Free ESMO Whitepaper)-IO Meeting. IBI110 in combination with sintilimab demonstrated encouraging efficacy and safety data in sqNSCLC. We will continue to provide updates on the PoC data for IBI110 and plan to initiate pivotal clinical studies. As immunotherapy moves into the next era, we are actively advancing the development of next-generation immune checkpoint inhibitors, among which IBI110 represents a high-potential LAG-3 asset, which we hope will benefit patients in need soon."

To learn more about Innovent’s R&D updates and activities, please visit View Source

About IBI110

IBI110 is an IgG4κ recombinant human anti-LAG-3 monoclonal antibody independently developed by Innovent Biologics. Based on the mechanism of action and preclinical data of IBI110, it is assumed that IBI110 can inhibit the immune checkpoint signaling to achieve anti-tumor effect, which may further improve the efficacy of immunotherapy, overcome the primary drug resistance, and overcome the drug resistance after anti-PD-1 /PD-L1 monoclonal antibody treatment3. Based on the urgent clinical needs, Innovent has carried out clinical studies to explore PK/PD characteristics of IBI110 single agent and combined with sintilimab in humans as well as its efficacy and safety in various advanced tumors. This clinical trial (NCT04085185) is the first in human clinical study of IBI110.

On December 8, 2022 Astrazeneca reported Initial results from the TROPION-PanTumor01 Phase I trial of datopotamab deruxtecan (Dato-DXd) showed encouraging and durable efficacy in patients with heavily pretreated hormone receptor (HR)-positive, HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in-situ hybridisation [ISH] negative) or HER2-negative (IHC 0) unresectable or metastatic breast cancer (Press release, AstraZeneca, DEC 8, 2022, View Source [SID1234624965]). Safety results were consistent with previous trials of datopotamab deruxtecan. Results were presented today at the 2022 San Antonio Breast Cancer Symposium (abstract #PD13-08).

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

In this cohort of TROPION-PanTumor01 (n=41), datopotamab deruxtecan demonstrated an objective response rate (ORR) of 27% as assessed by blinded independent central review (BICR). All responses were partial (n=11) and 56% of patients achieved stable disease (n=23). The disease control rate (DCR) was 85% and median progression-free survival (PFS) was 8.3 months (95% confidence interval [CI], 5.5-11.1). With median follow-up of 13.7 months, the median duration of response (DoR) and the median overall survival (OS) had not been reached with 59% of patients alive for more than one year.

Approximately 70% of breast cancer tumours are considered HR-positive and HER2-low or negative.1 For patients with HR-positive, HER2-low or negative metastatic breast cancer that progress on or are not suitable candidates for endocrine therapy, the current standard of care is single-agent chemotherapy.2

Funda Meric-Bernstam, Chair, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, and investigator in the TROPION-PanTumor01 trial, said: "Patients with HR-positive, HER2-low or negative metastatic breast cancer who are not eligible for endocrine therapy or have exhausted treatment options have a poor prognosis. These preliminary results with datopotamab deruxtecan in patients with heavily pretreated HR-positive, HER2-low or negative metastatic breast cancer are encouraging and warrant further evaluation in this setting."

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: "Many of these patients with metastatic breast cancer in TROPION-PanTumor01 had exhausted most of their available treatment options, having received a striking median of five prior regimens including a CDK4/6 inhibitor for nearly all patients. These promising results with datopotamab deruxtecan in such a heavily pretreated patient population support our strong belief that this TROP2-directed antibody drug conjugate has the potential to improve outcomes for patients with HR-positive, HER2-low or negative breast cancer in this, and possibly earlier settings."

Mark Rutstein, Global Head, Oncology Clinical Development, Daiichi Sankyo, said: "These results add to the growing body of data demonstrating the potential of datopotamab deruxtecan to treat certain types of metastatic breast cancer. We look forward to the continued evaluation of our TROP2-directed antibody drug conjugate, including comparisons to standard therapy in earlier lines of treatment for HR-positive, HER2-low or negative metastatic breast cancer through our ongoing TROPION-Breast01 Phase III trial."

Patients in the TROPION-PanTumor01 trial were heavily pretreated, receiving a median of five lines of prior regimens in the metastatic setting (range 3-10). Prior treatments included CDK4/6 inhibitors (95%), capecitabine (83%), taxanes (59%), anthracyclines (54%), neoadjuvant chemotherapy (37%), mTOR inhibitors (29%) and PI3KCA inhibitors (20%). As of data cut-off on 22 July 2022, five patients remained on study treatment.

The safety profile of datopotamab deruxtecan was consistent with previous data with no new safety signals identified. The most common Grade 3 or higher treatment-emergent adverse events (TEAEs) were decreased lymphocyte count (15%), stomatitis (10%), anaemia (7%), dyspnoea (2%) and fatigue (2%). Serious TEAEs were observed in six patients (15%), including one death due to dyspnoea that was not considered treatment-related. Treatment discontinuations due to an adverse event occurred in five patients (12%). No cases of Grade 3 or higher diarrhoea or febrile neutropenia were observed. One case of Grade 3 interstitial lung disease was adjudicated as treatment-related.

Summary of Results

Efficacy measure

Datopotamab deruxtecan (6mg/kg) n=41

Confirmed ORR, %i,ii

27% (n=11)

PR, %

27% (n=11)

SD, %

56% (n=23)

Non-CR/non-PD, %

2% (n=1)

PD, %

12% (n=5)

NE, %

2% (n=1)

DCR, %i,iii

85% (n=35)

Median DoR (months) (95% CI)i

NE (4.4-NE)

Median PFS (months) (95% CI)i

8.3 (5.5-11.1)

Median OS (months)

Not reached

CI, confidence interval; CR, complete response; DCR, disease control rate; DoR, duration of response; NE, not evaluable; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease
i As assessed by BICR
ii ORR is (CR + PR)
iii DCR is (CR + PR + SD + non-CR/non-PD)

AstraZeneca and Daiichi Sankyo have a broad clinical development programme for datopotamab deruxtecan in breast cancer, including the ongoing pivotal TROPION-Breast01 Phase III trial evaluating datopotamab deruxtecan in patients with HR-positive, HER2-low or negative, inoperable or metastatic breast cancer previously treated with chemotherapy.

Notes

HR-positive breast cancer
Breast cancer is the most common cancer and one of the leading causes of cancer-related deaths worldwide.3 More than two million breast cancer cases were diagnosed in 2020, with nearly 685,000 deaths globally.3

HR-positive breast cancer (expressing estrogen or progesterone receptors, or both) is the most common subtype of breast cancer with approximately 70% of breast cancer tumours considered HR-positive and HER2-low or negative.1

The growth of HR-positive breast cancer cells is often driven by estrogen receptors (ER), and endocrine therapies that target ER-driven disease are widely used as 1st-line treatment in the advanced setting, and often paired with cyclin-dependent kinase (CDK) 4/6 inhibitors.4-6 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.6 Once this occurs, the treatment options are limited – with chemotherapy being the current standard of care – and survival rates are low with 30% of patients anticipated to live beyond five years after diagnosis.1,2,6

Optimising endocrine therapy and overcoming resistance for patients with ER-driven disease at all stages of treatment as well as identifying new therapies for those who no longer have ER-driven disease are active areas of focus for breast cancer research.

TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is broadly expressed in several types of solid tumours, including HR-positive, HER2-low or negative breast cancer.7-8 TROP2 expression is an unfavourable prognostic factor for overall survival in all types of breast cancer.7

TROPION-PanTumor01
TROPION-PanTumor01 is a first-in-human, open-label, two-part, multicentre Phase I trial evaluating the safety and preliminary efficacy of datopotamab deruxtecan in patients with advanced solid tumours that have relapsed or are refractory to standard treatment or for which no standard treatment is available. The dose escalation portion of the trial enrolled patients with non-small cell lung cancer (NSCLC) to assess the safety and efficacy of datopotamab deruxtecan to determine the recommended dose for expansion (6mg/kg). The dose expansion part of TROPION-PanTumor01 is enrolling several different cohorts including patients with NSCLC, triple-negative breast cancer (TNBC), HR-positive, HER2-low or negative breast cancer, small cell lung cancer, urothelial, gastric, pancreatic, castration-resistant prostrate and esophageal cancer.

Safety endpoints include dose-limiting toxicities and serious adverse events. Efficacy endpoints include ORR, DoR, time to response, PFS and OS. Pharmacokinetic, biomarker and immunogenicity endpoints also are being evaluated.

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 three leading 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, via tetrapeptide-based cleavable linkers.

A comprehensive development programme called TROPION is underway globally with more than 10 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple TROP2-targetable tumours, including TNBC, HR-positive, HER2-low or negative breast cancer and NSCLC. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.