On June 6, 2022 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, the Company presented two posters with study results for CT041, an autologous CAR T-cell product candidate against protein Claudin18.2 (CLDN18.2) (Press release, Carsgen Therapeutics, JUN 6, 2022, View Source;301561407.html [SID1234615673]). The two posters included (1) results from the multicenter Phase 1b CT041 trial in the U.S. for patients with advanced gastric and pancreatic adenocarcinoma and (2) the safety and preliminary efficacy results from the Phase Ib/II CT041 study in China for patients with advanced gastric/gastroesophageal junction adenocarcinoma.

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The abstracts of the posters are listed below:

Abstract #2538: Multicenter Phase 1b Trial of Salvage CT041 CLDN18.2 – specific Chimeric Antigen Receptor T Cell Therapy for Patients with Advanced Gastric and Pancreatic Adenocarcinoma

A single-arm, open-label, Phase 1b trial (NCT04404595) was conducted in six centers in the U.S. CLDN18.2 positive patients who had gastric cancer or gastroesophageal junction cancer (GC/GEJ) with ≥ 2 prior lines of systemic therapy or pancreatic cancer (PC) with ≥ 1 prior line were eligible for the study. A preconditioning regimen with fludarabine, cyclophosphamide, and nab-paclitaxel (100 mg or 100 mg/m2; FNC) was given prior to CT041 infusion. Adverse events (AEs) were graded per CTCAE v5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded by ASTCT criteria. Tumor response was assessed per RECIST 1.1.

As of May 6, 2022, 14 patients had enrolled (5 GC/GEJ, 9 PC) with a median of 3 prior lines of therapy (range 1-5) and had received 18 total cycles of CT041. Fourteen patients were given by three dose levels (DL) including DL1 of 2.5-3.0×108 cells (n=6), DL2 of 3.75-4.0×108 cells (n=6) and DL3 of 6.0×108 cells (n=2).

Safety

No dose-limiting toxicities or treatment-related deaths were observed. No ≥ Grade 3 CRS or ICANS was observed. No gastrointestinal bleeding or acute gastric mucosal injury were reported. One patient did not have CRS. Among the 13 patients with CRS, 11 patients had Grade 1 and 2 patients had Grade 2.

Efficacy

In a subgroup of patients with GC/GEJ, an objective response rate (ORR) of 60% was reported, and one patient achieved complete response (CR). Additionally, tumor shrinkage was observed in 80% (4 of 5) of patients with stable disease (4 patients with PC). Median duration of response (mDOR) and progression-free survival (mPFS) have not been reached. Two patients who received DL3 did not have tumor response assessments by the data cutoff date. Dose-dependent responses were observed in DL1 and DL2. An ORR of 16.7% and a disease control rate (DCR) of 50% was observed in DL1. An ORR of 33.3% and a DCR of 83.3% were observed in DL2. Tumor response details are listed in the table below.

Tumor response by tumor type

GC/GEJ (n=5)

n (%)

PC (n=7)

n (%)

Complete response

1 (20)

0 (0)

Partial response

2 (40)

0 (0)

Stable disease

1 (20)

4 (57.1)

Progressive disease

1 (20)

3 (42.9)

Note: GC/GEJ= gastric cancer or gastroesophageal junction cancer; PC=pancreatic cancer.

Conclusion

In heavily pre-treated gastric cancer, CT041 CLDN18.2 CAR T cells may have significantly improved antitumor activity compared to historical treatment regimens.

Abstract #4017 Safety, Tolerability and Preliminary Efficacy Results in Patients with Advanced Gastric/Gastroesophageal Junction Adenocarcinoma from a Phase Ib/II Study of CLDN18.2 CAR T-cell Therapy (CT041)

This multicenter, open-label, Phase Ib/II study (NCT04581473) was conducted to evaluate the safety and efficacy in Chinese patients with GC/GEJ. In Phase Ib, CT041 dose levels of 2.5×108 and 3.75×108 cells were investigated using a 3 + 3 design.

Key eligibility criteria for the Phase Ib study: patients with CLDN18.2-positive expression confirmed by immunohistochemistry (IHC) staining (2+/3+ in ≥40% tumor cells), advanced GC/GEJ adenocarcinoma who were refractory to or intolerant of at least 2 prior treatments are eligible for this study. HER2–positive patients should have received standard anti–HER2 therapy.

As of December 22, 2021, 14 eligible patients with GC/GEJ were enrolled in Phase Ib, among which 57.1% had ≥ 3 metastatic organs and 92.9% had peritoneal dissemination. Most of the patients (85.7%) had received 2 prior treatments or a triple combination of fluoropyrimidine, oxaliplatin and paclitaxel. 35.7% of the patients had been exposed to PD-1/PD-L1 inhibitor. The baseline characteristics are shown in the table below.

Demographics and baseline characteristics

Total (N = 14)

Median age (range), year

44.5 (23–71)

Male, n (%)

6 (42.9%)

Eastern Cooperative Oncology Group performance status=1, n (%)

12 (85.7%)

Lauren classification, n (%)

Intestinal type

3 (21.4%)

Diffuse type

9 (64.3%)

Mixed type

2 (14.3%)

Signet ring cell carcinoma, n (%)

9 (64.3%)

Claudin18.2 staining, n (%)

2+

2 (14.3%)

3+

12 (85.7%)

HER2 expression, n (%)

Positive

1 (7.1%)

Negative

12 (85.7%)

Unknown

1 (7.1%)

Numbers of metastatic organs, n (%)

< 3

6 (42.9%)

≥ 3

8 (57.1%)

Peritoneal metastasis, n (%)

13 (92.9%)

Liver metastasis, n (%)

3 (21.4%)

Numbers of prior lines, n (%)

2*

12 (85.7%)

≥ 3

2 (14.3%)

Prior systemic therapies, n (%)

Fluorouracil

14 (100%)

Platinum

14 (100%)

Paclitaxel / nab–paclitaxel

13 (92.9%)

PD–1/PD-L1 inhibitor

5 (35.7%)

Tyrosine–kinase inhibitor

2 (14.3%)

* Five patients received a triple combination of fluoropyrimidine, oxaliplatin and paclitaxel as first line treatment.

All 14 patients received 1 cycle of bridging chemotherapy determined by the investigators, including 13 patients (92.9%) received FOLFIRI, and only 1 received 5–FU plus intraperitoneal nab–paclitaxel. All patients received preconditioning treatment (fludarabine 25 mg/m2 on d1–2, cyclophosphamide 250 mg/m2 on d1–3 and nab–paclitaxel 100 mg on d2) before CT041 infusion. All patients received at least one infusion (11 received 2.5×108 cells and 3 received 3.75×108 cells) of CT041 and 7 patients received two infusions. For the 7 patients who received two infusions, the median interval between infusions was 132 days (range 49–252 days).

Safety

No patients had dose–limiting toxicities or AEs leading to death. Thirteen patients had Grade 2 CRS, and only one patient had Grade 4 CRS, which was related to the patient’s disease burden, who fully recovered after corticosteroid treatment. No ICANS or gastrointestinal mucosal injury were reported.

Efficacy

Thirteen patients were evaluable and one patient withdrew from the study before any tumor assessment was performed. Eight of 14 (57.1%) patients achieved partial response at the first tumor assessment after the first CT041 infusion. Based on the investigators’ assessment, the ORR and DCR were 57.1% and 78.6% respectively.

While the median follow-up time was 8.8 months, the mPFS and median overall survival were 5.6 months and 10.8 months respectively. Seven patients were still alive by the cutoff date.

Conclusion

These preliminary results suggest that CT041 had manageable safety/tolerability profile and promising efficacy in patients with previously treated advanced GC/GEJ adenocarcinoma. This study is ongoing with further investigation of CT041 in confirmatory Phase II underway.

Dr. Raffaele Baffa, Chief Medical Officer of CARsgen Therapeutics Holdings Limited, said, "Solid tumors, including gastric cancer, are of high incidence globally. As treatment options for gastric cancer are still limited, there is a strong need for more innovative therapies. The updated clinical data of CT041 at ASCO (Free ASCO Whitepaper) 2022 are very encouraging in pre-treated GC/GEJ and PC patients, demonstrating significant efficacy and excellent tolerability, including the impressive ORR of 60% and a case of CR. We look forward to the continuing development of CT041 and we believe it can help more patients."

Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics Holdings Limited, said, "It is the first time that we presented the data for CT041 from registrational trials in China and the U.S. Following the publication of the results of an investigator-initiated trial of CT041 in Nature Medicine earlier in May, the updated results announced at ASCO (Free ASCO Whitepaper) 2022 further demonstrated the promising therapeutic efficacy and favorable safety of CT041. CT041 is currently the only CAR T-cell product candidate entering a confirmatory Phase II clinical trial for the treatment of solid tumors. We will spare no efforts to continue driving the global clinical development of CT041 to benefit more cancer patients worldwide."

About CT041

CT041 is an autologous CAR T-cell product candidate against the protein CLDN18.2 that has the potential to be the first-in-class globally. CT041 targets the treatment of CLDN18.2 positive solid tumors with a primary focus on GC/GEJ and PC. CT041 has demonstrated promising therapeutic efficacy and favorable safety in ongoing clinical trials. CARsgen believes that CT041 has the potential to become a backbone therapy for GC/GEJ and PC in the future and benefit a large population of patients worldwide.

As of the date of the announcement, CT041 is the only CLDN18.2-targeted CAR T-cell product candidate globally that is being studied in clinical trials with IND/CTA approvals from the FDA, the NMPA and Health Canada.

Active trials in CARsgen include investigator-initiated trials, a Phase Ib clinical trial for advanced GC/GEJ and PC and a confirmatory Phase II clinical trial for advanced GC/GEJ in China (CT041-ST-01, NCT04581473), and a Phase 1b/2 clinical trial for advanced gastric or pancreatic adenocarcinoma in North America (CT041-ST-02, NCT04404595). CARsgen also intends to conduct a pivotal Phase 2 clinical trial in North America in 2022.

In May 2022, the phase I trial interim results of an investigator-initiated trial of CT041 have been published in Nature Medicine. In this largest clinical trial for solid tumors to date, the CAR T-cell therapy showed unprecedented efficacy against solid tumors.

In 2020 and 2021, CT041 received Orphan Drug designation from the U.S. FDA for the treatment of GC/GEJ and Orphan Medicinal Product designation from the EMA for the treatment of advanced gastric cancer. In November 2021, CT041 was granted PRIME Eligibility by the EMA for the treatment of advanced gastric cancer. In January 2022, CT041 was granted Regenerative Medicine Advanced Therapy (RMAT) Designation by U.S. FDA for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma with CLDN18.2 positive tumors.

On June 6, 2022 Linnaeus Therapeutics, Inc. (Linnaeus), a privately held clinical-stage biopharmaceutical company focused on the development and commercialization of novel small-molecule oncology therapeutics, reported the presentation of clinical data from its phase 1/2 clinical trial of LNS8801 in combination with pembrolizumab in patients who have developed secondary resistance to anti–PD-1/L1 therapy at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Linnaeus Therapeutics, JUN 6, 2022, View Source [SID1234615672]).

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The poster is entitled, "Phase 1b study of the novel first-in-class G protein-coupled estrogen receptor (GPER) agonist, LNS8801, in combination with pembrolizumab in patients with immune checkpoint inhibitor (ICI)-relapsed and refractory solid malignancies."

In the dose-escalation portion of the study, LNS8801 demonstrated exceptional safety and tolerability. With monotherapy, no dose-limiting toxicities (DLTs) or treatment-related serious adverse events were observed, and the combination of LNS8801 and pembrolizumab was confirmed to be safe and tolerable with no DLTs observed. The recommended phase 2 dose of LNS8801 was identified as 125 mg daily as a monotherapy and in combination with pembrolizumab (200 mg every 3 weeks). Predictive, prognostic, and confirmatory biomarkers have been shown to correlate well with anticancer activity and clinical benefit. These biomarkers are being further validated and will aid in the selection of patients in future clinical studies.

The combination of LNS8801 with pembrolizumab has demonstrated strong signals of activity in patients with metastatic cancer who had previously benefited from and then developed secondary resistance to ICI therapy. An objective response rate of 15.4% was achieved, with 2 of 13 evaluable patients achieving confirmed partial responses. A disease control rate of 69.2% was observed, with 9 of 13 evaluable patients achieving partial responses or stable disease. Four patients have already remained on study longer than 6 months with ongoing benefit for the duration of therapy. The combination of LNS8801 and pembrolizumab is tolerable without unanticipated toxicities.

"We are very pleased to showcase these data at ASCO (Free ASCO Whitepaper)," commented Patrick Mooney, MD, CEO of Linnaeus. "LNS8801 continues to be extremely safe and well tolerated and shows very promising activity in combination with pembrolizumab. It is important to note that the disease control rate of ICI therapy alone in this patient population is expected to be very low, so it is exciting to see that the addition of LNS8801 to pembrolizumab is stopping progression in almost 70% of patients without any additional toxicity. We look forward to further exploration of LNS8801 alone and in combination, and we are encouraged by the continuing data we are seeing from these open cohorts."

About LNS8801
LNS8801 is an orally bioavailable, highly specific, and potent agonist of GPER whose activity is dependent on the expression of GPER. GPER activation by LNS8801 rapidly and durably depletes c-Myc protein levels. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory.

In the ongoing phase 1/2a study in humans, LNS8801 monotherapy has been safe and well tolerated. Additionally, LNS8801 has demonstrated target engagement, c-Myc protein depletion, and clinical benefit in some patients with advanced cancer.

On June 6, 2022 Senhwa Biosciences, Inc. (TPEx: 6492), a drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and novel coronaviruses, reported that it has received written approval from the Human Research Ethics Committee (HREC), Australia to begin a Phase I study evaluating Senhwa’s Pidnarulex, the 2019 PCF-Pfizer Global Challenge Awards winner will be used in combination with Pfizer’s PARP inhibitor, Talazoparib (Talzenna), to explore potential therapy in patients with metastatic The study will be conducted by Peter MacCallum Cancer Centre (PMCC), Senhwa’s clinical partner in Melbourne, Australia (Press release, Senhwa Biosciences, JUN 6, 2022, View Source [SID1234615671]).

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This Phase I trial of Pidnarulex and Talazoparib will be mainly funded by the US Prostate Cancer Foundation (PCF) and Pfizer. Senhwa will provide supplies of their study drug, Pidnarulex, in addition to some specific funding for the study.

Pfizer’s Talazoparib, an oral PARP inhibitor (PARPi), received FDA’s approval in October 2018 for the treatment of adults with deleterious or suspected deleterious germline BRCA mutation–positive, HER2-negative locally advanced or metastatic breast cancer. While BRCA1/2 deficient tumor cells are responsive to PARPi treatments, the development of PARPi resistance is common.

In the previous Phase I trial conducted by CCTG, Senhwa’s Pidnarulex demonstrated clinically significant and persist benefits in patients with specific tumor biomarkers, such as BRCA1/2, and PALB2 mutations, and who had been exposed to platinum and other chemotherapeutics.

"Pidnarulex, alone, has shown efficacy in tumor cells resistant to PARPi in the preclinical studies. Therefore, we think Pidnarulex demonstrates great potential as an alternative treatment for prostate cancer patients who have acquired resistance to PARPi or other chemotherapies," said Dr. John Soong, Chief Medical Officer of Senhwa Biosciences.

Prostate Cancer is the second most lethal cancer for men in the United States. Although nearly 70% of patients can be cured with surgery, once the cancer has metastasized, almost all patients develop into castration-resistance, with a median survival time of less than two years.

About Pidanrulex (CX-5461)

Specific mutations within the Homologous Recombination (HR) pathway may be exploited by Pidnarulex through a synthetic lethality approach by targeting the DNA repair defects in Homologous Recombination Deficiency (HRD) tumors. Specifically, Pidnarulex is designed to stabilize DNA G-quadruplexes of cancer cells which leads to disruption of the cell’s replication fork. While acting in concert with HR pathway deficiencies, such as BRCA1/2 mutations, replication forks stall and cause DNA breaks, ultimately resulting in cancer cell death.

On June 6, 2022 Shanghai Henlius Biotech, Inc. (2696.HK) reported that an international randomized phase 3 study (ASTRUM-005) of HANSIZHUANG (serplulimab), an anti-PD-1 mAb independently developed by Henlius, as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC) has been orally presented at 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Shanghai Henlius Biotech, JUN 6, 2022, View Source [SID1234615670]). Serplulimab is the first China-developed anti-PD-1 mAb in first-line treatment of lung cancer that was presented orally at ASCO (Free ASCO Whitepaper) Annual Meeting. The leading principal investigator is Professor Ying Cheng from Jilin Cancer Hospital.

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Professor Ying Cheng said, "ASTRUM-005 is the first and largest ES-SCLC international multi-center clinical study led by Chinese researchers for anti-PD-1 mAb. A total of 114 sites’ subjects were screened around the globe, with 31.5% being Caucasian. The study results demonstrated that serplulimab in combination with chemotherapy can significantly extend the median OS to 15.4 months when compared to the control group in first-line SCLC, gaining global recognition while leapfrogging immunotherapy treatment for SCLC patients."

Mr. Jason Zhu, President of Henlius, said, "HANSIZHUANG is an innovative mAb independently developed by Henlius. Based on the large number of unmet clinical needs, the company has implemented a comprehensive first-line treatment strategy for lung cancer with multiple clinical trials. Previously, the NDA of HANSIZHUANG for the treatment of ES-SCLC has been accepted by NMPA, which makes HANSIZHUANG potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. We are hoping that the approval comes soon to mend the gap and bring a new treatment option to patients living with ES-SCLC. Going forward, we will proactively promote more clinical research, thereby benefiting more patients around the world."

ASTRUM-005 has set up a total of 128 sites in China, Turkey, Poland, Georgia, etc. and enrolled 585 subjects from 114 sites, among whom 31.5% were Caucasian. In December 2021, ASTRUM-005 met its primary study endpoint of the overall survival (OS) in the interim analysis and demonstrated HANSIZHUANG with a manageable safety profile. The global clinical data lays a solid foundation for future applications across the world. ASTRUM-005 results are as follows:

Title

Serplulimab, a novel anti-PD-1 antibody, plus chemotherapy versus chemotherapy alone as first-line treatment for extensive-stage small-cell lung cancer: An international randomized phase 3 study (Abstract No. 8505)

Study design

This randomized, double-blind, international, multicenter, phase 3 clinical study aimed to compare the efficacy and safety of serplulimab with placebo when combined with chemotherapy (carboplatin-etoposide) in previously untreated patients with ES-SCLC. Enrolled patients were randomized 2:1 to receive intravenous infusion of either serplulimab or placebo in combination with chemotherapy every three weeks until disease progression, death, intolerable toxicity, withdrawal of informed consent or other reasons specified in the protocol (whichever occurred first). The primary endpoint of this study was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), safety, pharmacokinetic characteristics, and immunogenicity.

Results

As of October 22, 2021, 585 eligible patients were randomized (serplulimab group, n=389; placebo group, n=196), with a median follow-up duration of 12.3 months. The median OS in the serplulimab group and the placebo group were 15.4 (95% CI 13.3–NE) and 10.9 (95% CI 10.0–14.3) months, respectively, with a hazard ratio (HR) of 0.63 (95% CI 0.49–0.82; p<0.001). The 24-month OS rate in the two treatment groups were 43.1% and 7.9%, respectively. Median PFS assessed by the independent radiology review committee (IRRC) per RECIST v1.1 was 5.7 months in the serplulimab group and 4.3 months in the placebo group (HR 0.48, 95% CI 0.38–0.59). Efficacy improvements were also observed in ORR (80.2% vs. 70.4%) and DOR (median, 5.6 vs. 3.2 months) as assessed by IRRC per RECIST v1.1.

Grade ≥3 treatment related adverse events (TRAEs) related to serplulimab or placebo were reported by 129 (33.2%) and 54 (27.6%) patients in the respective groups. Incidence of immune-related adverse events (irAEs) was higher in the serplulimab group compared to the placebo group (37.0% vs. 18.4%), and was similar to the approved PD-1/PD-L1 antibodies.

Conclusions

The results demonstrated that serplulimab in combination with carboplatin-etoposide significantly improved OS as first-line treatment in ES-SCLC patients. The safety profile was consistent with previous studies. Serplulimab, as the first anti-PD-1 antibody showing OS benefit in untreated ES-SCLC patients, possess the potential to provide an alternative treatment option for this patient population worldwide.

About HANSIZHUANG

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. Up to date, 1 indication is approved for marketing in China, 2 NDAs have been accepted by the NMPA, and 9 clinical trials are ongoing across the world.

HANSIZHUANG was approved by the NMPA for the treatment of MSI-H solid tumors in March 2022 and actively promotes its synergy with in-house products of the company and innovative therapies. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 9 clinical trials on immuno-oncology combination therapies worldwide in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. As of now, the company has enrolled more than 2,800 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of Caucasian is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The NDAs of the treatment for squamous non-small cell lung cancer (sqNSCLC) and the first-line treatment of extensive small-cell lung cancer (ES-SCLC) have been accepted by the NMPA. Furthermore, HANSIZHUANG was recommended by the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer (SCLC) for the treatment of ES-SCLC and was also granted orphan drug designation by the FDA for treatment of SCLC. The MAA of ES-SCLC is expected to be filed in the EU in 2022, which makes HANSIZHUANG potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. In the field of esophageal squamous cell carcinoma, the phase 3 clinical trial of HANSIZHUANG in combination with chemotherapy has met the co-primary endpoints.

On June 6, 2022 The Menarini Group ("Menarini") and Radius Health, Inc. ("Radius") (NASDAQ: RDUS) (collectively, the "Companies") reported the presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting of data from the EMERALD phase 3 clinical trial (NCT03778931) (Press release, Menarini, JUN 6, 2022, View Source [SID1234615669]). In a non-pre-specified subgroup analysis of patients with ER+/HER2− metastatic breast cancer (mBC) without prior chemotherapy in the metastatic setting, elacestrant significantly prolonged progression-free survival (PFS) compared to standard of care (SOC) endocrine therapy.

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EMERALD study met both of its pre-specified primary end points of progression-free survival (PFS) in the overall population and in patients with ESR1 mutation (mESR1).1

77.8% (n=371) out of the 477 patients enrolled in the trial had not received prior chemotherapy in the metastatic setting for ER+/HER2−mBC. Among these patients, elacestrant showed the following results compared to SOC:
– 31% reduction in the risk of progression or death in all patients (HR=0.681 [95% CI: 0.520 – 0.891]; P=0.00388) and prolonged median PFS (3.68 vs 1.97 months).
– 46% reduction in the risk of progression or death in patients with mESR1 (HR=0.535 [95% CI: 0.356 – 0.799]; P=0.00235) and prolonged median PFS (5.32 vs 1.91 months).

At 6 months, PFS rate with elacestrant was 38.18% vs. 23.47% with SOC in the overall population, and 43.79% vs. 23.83% in the ESR1 mutation population.

PFS rate at 12 months with elacestrant was 27.12% vs. 12.19% with SOC in the overall population, and 31.48% vs. 12.36% in the ESR1 mutation population.

In exploratory subgroup analyses, elacestrant significantly reduced the risk of progression or death and prolonged median PFS vs fulvestrant in all patients without prior chemotherapy (HR=0.636 [95% CI: 0.465-0.868]; median PFS 3.68 vs 1.97 months; P=0.0032), and in patients with mESR1 without prior chemotherapy (HR=0.487 (95% CI: 0.310-0.761; median PFS 5.32 vs 1.91 months; P=0.0015).

Elacestrant had a manageable safety profile in patients without prior chemotherapy consistent with the overall population.1

Dr. Virginia Kaklamani, breast medical oncologist and professor of medicine, UT Health San Antonio, MD Anderson Cancer Center, commented, "Elacestrant is a potential exciting new endocrine therapy after progression on a CDK4/6 inhibitor in women with ER+ metastatic breast cancer. The EMERALD trial showed that elacestrant is active even in patients whose tumors harbor an ESR1 mutation. This subset analysis additionally showed that patients who have not previously been treated with chemotherapy in the metastatic setting had longer progression free survival up to 5.32 months."

Menarini plans to pursue combination studies and study the potential of elacestrant to be effective in addressing the highest unmet needs for ER+/HER2-patients.

Poster Presentation: 477

Abstract Title: Subgroup analysis of patients with no prior chemotherapy in EMERALD: A phase 3 trial evaluating elacestrant, an oral selective estrogen receptor degrader (SERD), vs investigator’s choice of endocrine monotherapy for ER+/HER2- advanced/metastatic breast cancer (mBC)

Abstract Number: 1100

Poster Session: Breast Cancer – Metastatic

About Elacestrant (RAD1901) and EMERALD Phase 3 Study

Elacestrant is an investigational selective estrogen receptor degrader (SERD), out-licensed to Menarini Group, which is being evaluated for potential use as a once daily oral treatment in patients with ER+/ HER2- advanced breast cancer. In 2018, elacestrant received fast track designation from the FDA. Preclinical studies completed prior to EMERALD indicate that the compound has the potential for use as a single agent or in combination with other therapies for the treatment of breast cancer. The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+/HER2- advanced/metastatic breast cancer patients. The study enrolled 477 patients who have received prior treatment with one or two lines of endocrine therapy, including a CDK 4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator’s choice of an approved hormonal agent. The primary endpoint of the study was progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations. Secondary endpoints included evaluation of overall survival (OS), objective response rate (ORR), and duration of response (DOR).

References

1. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol. 2022 May 18:JCO2200338. doi.org: 10.1200/JCO.22.00338. Epub ahead of print.