DZD1516 / Dizal Pharma - LARVOL DELTA

DZD1516 in Combination With Trastuzumab and Capecitabine, or in Combination With T-DM1, in Patients With Metastatic HER2 Positive Breast Cancer (clinicaltrials.gov) - P1 | N=23 | Completed | Sponsor: Dizal Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Preclinical and clinical activity of DZD1516, a full blood-brain barrier-penetrant, highly selective HER2 inhibitor. (PubMed, Breast Cancer Res) - P1 | "DZD1516 provides positive proof of concept for an optimal HER2 inhibitor with high BBB penetration and HER2 selectivity. Further clinical evaluation of DZD1516 is warranted, with the RP2D being 250 mg BID."

Journal • Preclinical • Breast Cancer • CNS Tumor • Dermatology • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pain • Solid Tumor • EGFR

Dizhe Medicine: Dizhe Medicine: Voluntary disclosure of the announcement on the publication of DZD1516 research results in “Breast Cancer Research“ [Google translation] (Stockstar) - P1 | N=23 | NCT04509596 | Sponsor: Dizal Pharmaceuticals | "Preclinical studies have shown that the selectivity of DZD1516 for HER2 is more than 300 times higher than that of wild-type EGFR. DZD1516 monotherapy exhibited significant antitumor activity in HER2-positive brain metastases, meningeal metastases, and subcutaneous xenograft mouse models . When DZD1516 was combined with HER2 ADC drugs T-DM1 (emmettrastuzumab ) or T-DXd (detrastuzumab), the anti-tumor effect was further enhanced, which was better than either single agent....The results of the study showed that patients showed good safety. Since DZD1516 has a selectivity of more than 300 times for wild-type EGFR, in the above-mentioned Dose Range No adverse events related to inhibition of wild-type EGFR were reported. The Kpuu,CSF (ratio of free drug concentration in cerebrospinal fluid to plasma) of DZD1516 in patients was 2.1, confirming that it can completely penetrate the blood-brain barrier."

P1 data • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Updated data from the phase 1 trial of DZD1516, a BBB-penetrant selective HER2 inhibitor, in patients with HER2 positive metastatic breast cancer (SABCS 2022) - P1 | "DZD1516 is a full BBB-penetrant HER2 inhibitor. Consistent with its high selectivity, no wild-type EGFR-related AEs have been reported. The updated data will be presented at the meeting."

Clinical • P1 data • Breast Cancer • CNS Tumor • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • EGFR

DZD1516 With CSF Penetration Has Antitumor Activity in Heavily Pretreated HER2+ Metastatic Breast Cancer (OncLive) - P1 | N=23 | NCT04509596 | Sponsor: Dizal Pharmaceuticals | "DZD1516, a reversible and selective HER2 TKI with full blood–brain barrier (BBB) penetration led to tumor responses, including in patients with baseline central nervous system (CNS) metastases, in a phase 1 study of patients with metastatic HER2-positive breast cancer....DZD1516 was well tolerated at 25 to 250 mg twice daily (dose-limiting toxicities were reported only in the 300-mg twice daily cohort). Therefore, 250 mg was defined as the maximum-tolerated dose....After twice daily dosing for 15 days, an approximate 2-fold accumulation of DZD1516 was observed systemically at doses 200 mg or lower. The combined exposure of DZD1516 and its active metabolite (DZ2678) generally increased with an increase in the dosage."

P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology

Preclinical and early clinical safety and pharmacokinetics data of DZD1516, an BBB-penetrant selective HER2 inhibitor for the treatment of HER2 positive metastatic breast cancer (SABCS 2021) - P1 | "Preclinical and preliminary clinical data showed that DZD1516 is a full BBB-penetrant HER2 inhibitor, with excellent safety profile. Further clinical evaluation of its safety and efficacy is ongoing. Table 1."

PK/PD data • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • EGFR

Clinical safety and pharmacokinetics (PK) data of DZD1516, an BBB-penetrant selective HER2 inhibitor for the treatment of HER2-positive metastatic breast cancer (ESMO 2022) - P1 | "Consistent with its high selectivity, no wild-type EGFR related AEs have been reported. Further clinical evaluation of DZD1516 is warranted."

Clinical • PK/PD data • HER2 Positive Breast Cancer • Oncology • EGFR • HER-2

Early clinical safety and pharmacokinetics data of DZD1516, an BBB-penetrant selective HER2 inhibitor for the treatment of HER2-positive metastatic breast cancer. (ASCO 2022) - P1 | "Preliminary clinical data showed that DZD1516 is a full BBB-penetrant HER2 TKI, with good safety profile. Consistent with its high selectivity, no wide type EGFR related AEs have been reported. Further evaluation of its safety and efficacy is ongoing."

Clinical • PK/PD data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pain • Solid Tumor • EGFR • HER-2

Dizal Announces Positive Phase I Clinical Trial Results for DZD1516 in Treating HER2 Breast Cancer at 2022 ESMO (PRNewswire) - P1, N=23 | NCT04509596 | Sponsor: Dizal Pharmaceuticals | "DZD1516 was well tolerated at doses ≤ 250 mg, and in consistent with its high selectivity, no wild-type EGFR-related AEs have been reported. Thus, 250 mg was defined as MTD. In patients, mean Kpuu,CSF was 2.1 for DZD1516 across the dose range, indicating full penetration of DZD1516 through human BBB."

P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

DZD1516 in Combination With Trastuzumab and Capecitabine, or in Combination With T-DM1, in Patients With Metastatic HER2 Positive Breast Cancer (clinicaltrials.gov) - P1 | N=23 | Active, not recruiting | Sponsor: Dizal Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=94 ➔ 23

Combination therapy • Enrollment change • Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Dizal to Demonstrate the Strength and Rapid Acceleration of its Clinical Portfolio at ASCO 2022 (PRNewswire) - "Dizal will present clinical results and updates from its four therapeutic candidates in solid tumors and hematologic malignancies at the 2022 Annual Meeting of the American Society of Cancer Oncology (ASCO) being held on June 3-7, 2022. New data from Dizal's investigational cancer medicines demonstrate the rapid progression of its oncology pipeline."

EGFR exon 20 • P1 data • P1/2 data • Breast Cancer • Hematological Malignancies • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma

DZD1516 in Combination With Trastuzumab and Capecitabine, or in Combination With T-DM1, in Patients With Metastatic HER2 Positive Breast Cancer (clinicaltrials.gov) - P1; N=94; Recruiting; Sponsor: Dizal Pharmaceuticals; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

"(I was on ds8201a w/nivolamab). Now on plain Enhertu. Did ZW25 a couple yrs back. Now info gathering on DZD1516 (oral single agent and 👍🏻#cns #lmd #bcbm) just in case 🤷🏻‍♀️" (@CANsurvive)

Clinical

DZD1516 in Combination With Trastuzumab and Capecitabine, or in Combination With T-DM1, in Patients With Metastatic HER2 Positive Breast Cancer (clinicaltrials.gov) - P1; N=94; Not yet recruiting; Sponsor: Dizal Pharmaceuticals

Clinical • Combination therapy • New P1 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor