SCR-6852 / Simcere - LARVOL DELTA

The activity of SIM0270 alone or in combination with everolimus or palbociclib in ER-positive, HER2-negative breast cancer patients with brain metastases (ESMO Asia 2025) - P1 | "Observed encouraging clinical benefits support further investigation for the use of SIM270 in combination with palbociclib or everolimus in ER-positive, HER2-negative breast cancer patients with BM."

Clinical • Combination therapy • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SIMRISE: A randomized phase III trial evaluating SIM0270 in combination with everolimus versus treatment of physician's choice in patients with ER+/HER2- advanced breast cancer, previously treated with CDK4/6 inhibitors. (ASCO 2025) - P3 | "Patients are randomized in a 1:1 ratio to receive either SIM0270 + everolimus or TPC (exemestane + everolimus or fulvestrant). Clinical trial information: NCT06680921. Research Sponsor: Simcere Zaiming Pharmaceutical Co., Ltd."

Clinical • Combination therapy • Metastases • P3 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SIM0270 in combination with palbociclib in patients with ER+/ HER2- advanced breast cancer: The phase Ib study. (ASCO 2025) - P1 | "The key inclusion criteria for dose escalation and dose expansion were the same as follows: ≥ 1 prior endocrine therapy (ET) with disease recurrence/ progression while being treated with adjuvant ET for ≥ 24 months and/or first line ET for ≥ 6 months in advanced setting; ≤2 prior chemotherapies in advanced setting; and prior fulvestrant was allowed. SIM0270 in combination with palbociclib showed acceptable safety and tolerability, promising clinical activity in patients with ER+/HER2- advanced breast cancer."

Clinical • Combination therapy • Metastases • P1 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Neutropenia • Oncology • Solid Tumor • ER • HER-2

Dr Zhang on the Efficacy of SIM0270 Plus Everolimus in ER+/HER2− Advanced Breast Cancer (OncLive) - P1b | N=214 | NCT05293964 | Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd. | "Jian Zhang, MD, Fudan University Shanghai Cancer Center, discusses results from the phase Ib trial (NCT05293964) evaluating SIM0270, a brain-penetrant oral selective estrogen receptor degrader (SERD), in combination with everolimus (Afinitor) in patients with estrogen receptor (ER)–positive, HER2-negative advanced breast cancer, including those with brain metastases. In the overall population, the combination demonstrated a median PFS of 8.2 months (95% CI, 4.96-not estimable [NE]). For patients with baseline ESR1 wild-type tumors, the median PFS was also 8.2 months (95% CI, 3.71-NE), whereas the PFS was not reached for those with ESR1-mutated tumors, suggesting enhanced efficacy in this subgroup. The confirmed objective response rate was 16.7%, and the clinical benefit rate, defined as complete response (CR), partial response, or stable disease lasting at least 24 weeks, was 60%."

P1 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

A Study of SIM0270 Combined with Everolimus Vs. Treatment of Physician's Choice in Patients with ER+/HER2- Advanced Breast Cancer (SIMRISE) (clinicaltrials.gov) - P3 | N=460 | Recruiting | Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd. | Initiation date: Feb 2025 ➔ Nov 2024

Metastases • Trial initiation date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

SIM0270, a brain-penetrant oral SERD, in combination with everolimus in patients with ER+/HER2- advanced breast cancer: the phase Ib study. (SABCS 2024) - P1 | "Key inclusion criterias of cohorts B and B1 were same as follows: ≤2 prior chemotherapies and allowed to have received prior fulvestrant or/and CDK4/6 inhibitors in the advanced setting. SIM0270 in combination with everolimus showed acceptable safety and tolerability, comparable to BOLERO-2 trial of exemestane +everolimus, along with promising evidence of clinical activity in patients with ER+/HER2- aBC. Further data will be presented at the meeting."

Clinical • Combination therapy • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Updated analyses from a Phase I study of the brain-penetrant oral SERD- SIM0270 in patients with ER-positive, HER2-negative advanced breast cancer. (SABCS 2024) - P1 | "In the expansion cohort of patients with ER+/HER2- locally advanced or metastatic breast cancer, SIM0270 monotherapy demonstrated promising evidence of clinical activity based on ORR and CBR that compared favorable to historical controls despite extensive pre-treatment including chemotherapies, CDK4/6 inhibitors and fulvestrant, which were enhanced in the subgroup patients refractory to the last treatment of patients with ESR1 mutations. SIM0270 monotherapy was well tolerated with manageable AE profile and low number of treatment discontinuation due to related AEs observed in the dose escalation part was maintained during cohort expansion part at dose of 60mg QD. Additional analyses are ongoing."

Clinical • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Evaluate the Effects of Food on the Pharmacokinetics of SIM0270 (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd. | Recruiting ➔ Completed | N=32 ➔ 16

Enrollment change • Trial completion

Phase I Study to Evaluate SIM0270 Alone or in Combination in ER+, HER2- Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=214 | Active, not recruiting | Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

A Study of SIM0270 Combined with Everolimus Vs. Treatment of Physician's Choice in Patients with ER+/HER2- Advanced Breast Cancer (SIMRISE) (clinicaltrials.gov) - P3 | N=460 | Recruiting | Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

Mass Balance Clinical Trial of SIM0270 (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd. | Recruiting ➔ Active, not recruiting | N=10 ➔ 6

Enrollment change • Enrollment closed

A Study of SIM0270 Combined with Everolimus Vs. Treatment of Physician's Choice in Patients with ER+/HER2- Advanced Breast Cancer (SIMRISE) (clinicaltrials.gov) - P3 | N=460 | Not yet recruiting | Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.

Metastases • New P3 trial • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

Mass Balance Clinical Trial of SIM0270 (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.

New P1 trial

Evaluate the Effects of Food on the Pharmacokinetics of SIM0270 (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.

New P1 trial

A first-in-human phase 1 study of SIM0270, a brain-penetrant oral selective estrogen receptor degrader (SERD), in patients with ER+/ HER2- locally advanced or metastatic breast cancer (SABCS 2023) - P1 | " This Phase 1 study evaluates the safety, pharmacokinetics and preliminary anti-tumor activity of SIM0270 as monotherapy and/or in combination with palbociclib or everolimus in patients with HR+/HER2- advanced or metastatic breast cancer. Single-agent SIM0270 was well tolerated and showed favorable antitumor activity in heavily pretreated advanced or metastatic ER+/HER2- breast cancer patients, including those previously treated with CDK4/6 inhibitors and fulvestrant. Phase 1a dose expansion with single-agent SIM0270 is ongoing, and the RP2D will be determined based on further accumulative data of tolerability and efficacy. (NCT05293964)"

Clinical • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SIM0270 Demonstrates Early Antitumor Activity in ER+/HER2– Advanced/Metastatic Breast Cancer (OncLive) - P1 | N=210 | NCT05293964 | Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd | "The brain-penetrant oral selective estrogen receptor degrader (SERD) SIM0270 exhibited a favorable safety profile and early signals of antitumor activity in patients with estrogen receptor (ER)–positive, HER2-negative locally advanced or metastatic breast cancer, including those with ESR1 mutations...Based on findings derived from the first-in-human study, dose-limiting toxicities (DLTs) were reported in 4 patients. Two patients, 1 each in the 200 mg and 300 mg cohorts, had grade 3 QT prolongation, and 2 patients in the 300 mg cohort had grade 3 dizziness. All DLTs were resolved through dose interruptions and reductions...Overall, patients had a median age of 55 years, 82% had an ECOG performance status (PS) of 1, and 68% were post-menopausal...Trial enrollment with SIM0270 at the 60-mg dose is ongoing. The phase 1b portion of the trial is concurrently investigating SIM0270 in combination with..."

P1 data • Trial status • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

SCR-6852, an oral and highly brain-penetrating estrogen receptor degrader (SERD), effectively shrinks tumors both in intracranial and subcutaneous ER + breast cancer models. (PubMed, Breast Cancer Res) - "SCR-6852 is a novel SERD with high potency in inducing ERα protein degradation and pure antagonistic activity on ERɑ signaling in vitro and in vivo. Due to the high brain penetrability, SCR-6852 could be used to treat breast patients with brain metastasis."

Journal • Preclinical • Brain Cancer • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • ER

Phase I Study to Evaluate SIM0270 Alone or in Combination in ER+, HER2- Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=210 | Recruiting | Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd. | N=146 ➔ 210

Enrollment change • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Phase I Study to Evaluate SCR-6852 Alone or in Combination in ER+, HER2- Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=146 | Recruiting | Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Phase I Study to Evaluate SCR-6852 Alone or in Combination in ER+, HER2- Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=146 | Not yet recruiting | Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.

New P1 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2