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.

On December 8, 2022 Astrazeneca reported Detailed results from the SERENA-2 Phase II trial showed AstraZeneca’s next-generation oral selective estrogen receptor degrader (ngSERD) camizestrant demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) at both 75mg and 150mg dose levels versus Faslodex (fulvestrant) 500mg in post-menopausal patients with estrogen receptor (ER)-positive locally advanced or metastatic breast cancer, previously treated with endocrine therapy (Press release, AstraZeneca, DEC 8, 2022, View Source [SID1234624964]). Results will be presented today in an oral presentation at the 2022 San Antonio Breast Cancer Symposium (SABCS).

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In the overall population, camizestrant significantly reduced the risk of disease progression or death by 42% at a 75mg dose (based on a hazard ratio [HR] of 0.58, 90% confidence interval [CI] 0.41-0.81; p=0.0124; median PFS of 7.2 versus 3.7 months) and 33% at a 150mg dose (HR 0.67, 90% CI 0.48-0.92; p=0.0161; median PFS of 7.7 versus 3.7 months) compared to Faslodex, the current SERD standard of care.

Among the prespecified subgroup of patients with ESR1 mutations – comprising 36.7% of the trial population – camizestrant showed a 67% reduction in the risk of disease progression or death at a 75mg dose (HR 0.33, 90% CI 0.18-0.58; median PFS of 6.3 versus 2.2 months) and a 45% reduction at a 150mg dose (HR 0.55, 90% CI 0.33-0.89; median PFS of 9.2 versus 2.2 months) compared to Faslodex. Efficacy was also seen in patients without a detectable ESR1 mutation, with a 22% and 24% reduction in the risk of disease progression or death (HR 0.78, 90% CI 0.50-1.22 and HR 0.76, 90% CI 0.48-1.20) respectively for the 75mg and 150mg dose levels.

A clinically meaningful PFS benefit was also observed across other prespecified subgroups, including in patients previously treated with prior cyclin-dependent kinase (CDK) 4/6 inhibitors, those with lung and/or liver metastases and those with ER-driven disease.

Mafalda Oliveira, MD, PhD, Vall d’Hebron Hospital and Vall d‘Hebron Institute of Oncology in Barcelona, Spain, and lead investigator for the SERENA-2 Phase II trial, said: "These data reflect an important step toward a potential new treatment option for patients with advanced ER-positive disease. Based on the SERENA-2 results, camizestrant was well tolerated at both doses and significantly improved patient outcomes, nearly doubling median progression-free survival in this setting compared with the current SERD standard of care."

Cristian Massacesi, Chief Medical Officer & Oncology Chief Development Officer, Oncology R&D, AstraZeneca, said: "SERENA-2 showed a meaningful improvement over fulvestrant, demonstrating the potential of camizestrant, our next-generation SERD, to optimise outcomes for patients with advanced ER-driven breast cancer, irrespective of ESR1 mutation status and prior treatment with CDK4/6 inhibitors. Our focus on bringing new medicines to patients across the breast cancer spectrum is unwavering and we look forward to additional findings from our ongoing Phase III development programme for camizestrant including SERENA-4 and SERENA-6."

Summary of results: SERENA-2

Efficacy measure

Camizestrant (75mg)

Camizestrant (150mg)

Faslodex (500mg)

Primary endpoint

Overall population (n)

74

73

73

Median PFS (months)

7.2

7.7

3.7

Adjusted HR (90% CI)

0.58 (0.41-0.81)

0.67 (0.48-0.92)

–

P-value

0.0124*

0.0161*

–

Prespecified sub-populations of interest

ESR1m detected (n)

22

26

35

Median PFS (months)

6.3

9.2

2.2

Adjusted HR (90% CI)

0.33 (0.18-0.58)

0.55 (0.33-0.89)

–

ESR1m not detected (n)

51

46

37

Median PFS (months)

7.2

5.8

7.2

Adjusted HR (90% CI)

0.78 (0.50-1.22)

0.76 (0.48-1.20)

–

Prior treatment with CDK4/6 inhibitors (n)

38

37

37

Median PFS (months)

5.5

3.8

2.1

Adjusted HR (90% CI)

0.49 (0.31-0.75)

0.68 (0.44-1.04)

–

Presence of lung and/or liver metastasis (n)

43

43

43

Median PFS (months)

7.2

5.6

2.0

Adjusted HR (90% CI)

0.43 (0.28-0.65)

0.55 (0.37-0.82)

–

Evidence of ER-driven disease (n)

50

53

53

Median PFS (months)

7.4

12.0

3.2

Adjusted HR (90% CI)

0.53 (0.35-0.79)

0.58 (0.39-0.86)

–

*Statistically significant; HR, hazard ratio (adjusted for stratification factors [prior use of CDK4/6i and presence of lung and/or liver metastases]); CI, confidence interval; PFS, progression free survival; ESR1m, ESR1 mutation.

Camizestrant was generally well tolerated, and its safety profile was consistent with that observed in previous trials with no new safety signals identified. The most frequent treatment-emergent adverse events (TEAEs) were photopsia (12.2%, 24.7%, 35.0% and 0%) and bradycardia (5.4%, 26.0%, 40.0% and 0%), for 75mg, 150mg or 300mg camizestrant or fulvestrant, respectively, all of which were Grade 1 or 2. TEAEs at Grade 3 or higher occurred in 1.4%, 2.7%, 5.0% and 1.4% of patients in the 75mg, 150mg and 300mg camizestrant or fulvestrant arms, respectively, with only two patients in the 75mg camizestrant arm and no patients in the 150mg, 300mg camizestrant or fulvestrant arms discontinuing therapy due to TEAEs.

AstraZeneca has a broad clinical development programme for camizestrant in advanced breast cancer. The SERENA-6 Phase III trial is assessing camizestrant in combination with CDK4/6 inhibitors for the 1st-line treatment of patients with HR-positive metastatic breast cancer who have developed detectable ESR1 mutations during treatment with aromatase inhibitors, and the SERENA-4 Phase III trial is evaluating camizestrant plus palbociclib (CDK4/6 inhibitor) for the 1st-line treatment of patients with HR-positive, locally advanced or metastatic breast cancer. The indication sought for SERENA-6 has been granted Fast Track Designation by the US Food and Drug Administration.

Notes

Hormone Receptor (HR)-positive breast cancer
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.1 More than two million patients were diagnosed with breast cancer in 2020, with nearly 685,000 deaths globally.1

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.2

The growth of HR-positive breast cancer cells is often driven by estrogen receptors (ER),3 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.4,5 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.5 Once this occurs, the treatment options are limited5 – with chemotherapy being the current standard of care6 – and survival rates are low with 30% of patients anticipated to live beyond five years after diagnosis.2

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.

SERENA-2
SERENA-2 is a randomised, open-label, parallel group, multicentre Phase II trial evaluating camizestrant at several dose levels compared to Faslodex in advanced ER-positive, HER2-negative breast cancer. The primary endpoints are PFS defined by response evaluation criteria in solid tumours (RECIST) version 1.1 for 75mg camizestrant versus Faslodex and for 150mg camizestrant versus Faslodex. 240 patients were randomised to receive camizestrant or Faslodex until disease progression. Secondary endpoints include safety, objective response rate and clinical benefit rate at 24 weeks.

Camizestrant
Camizestrant is a potent, next-generation oral SERD and pure ERα antagonist, that has demonstrated anti-cancer activity across a range of preclinical models, including those with ER-activating mutations.

AstraZeneca has a broad clinical development programme evaluating the safety and efficacy of camizestrant when used as a monotherapy or in combination with other agents to address a number of areas of unmet need in HR-positive breast cancer.

In addition to SERENA-2 and the ongoing SERENA-4 and SERENA-6 trials, the SERENA-1 Phase I trial demonstrated that camizestrant is well tolerated and has a promising anti-tumour profile when administered alone or in combination with palbociclib, a CDK4/6 inhibitor. Combinations with other agents are ongoing in SERENA-1.

On December 8, 2022 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that the National Medical Products Administration ("NMPA") in China has granted DANYELZA (naxitamab-gqgk) 40mg/10ml conditional approval (Press release, Y-mAbs Therapeutics, DEC 8, 2022, View Source [SID1234624963]). DANYELZA will be marketed in China by Y-mAbs’ partner SciClone Pharmaceuticals (Holdings) Limited ("SciClone Pharmaceuticals").

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DANYELZA is a humanized, monoclonal antibody that targets the ganglioside GD2, which is highly expressed in various neuroectoderm-derived tumors and sarcomas. DANYELZA is administered to patients three times in a week in an outpatient setting and the treatment is repeated every four weeks.

DANYELZA is indicated, in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF"), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. Continued approval for this indication may be contingent upon verification and description of clinical benefits in a confirmatory trial, Study 201, where no less than 10 patients shall be enrolled in China.

"Today is an important day for children living with refractory/relapsed high-risk neuroblastoma in China. It’s very exciting to see this treatment conditionally approved in such a substantial territory after a solid joint effort by our Chinese partner SciClone Pharmaceuticals and the development team at Y-mAbs," said Thomas Gad, founder, President and Interim CEO.

Researchers at Memorial Sloan Kettering Cancer Center ("MSK") developed DANYELZA, which is exclusively licensed by MSK to Y-mAbs. MSK has institutional financial interests related to the compound and Y-mAbs.

About DANYELZA (naxitamab-gqgk)

DANYELZA (naxitamab-gqgk) is indicated, in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF"), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. This indication was approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefits in a confirmatory trial. DANYELZA includes a Boxed Warning for serious infusion-related reactions, such as cardiac arrest and anaphylaxis, and neurotoxicity, such as severe neuropathic pain and transverse myelitis. See full Prescribing Information for complete Boxed Warning and other important safety information.