This study is a multicenter, open-label study designed to evaluate SPR1020 in adult patients with advanced solid tumors. The study aims to characterize the safety, tolerability, pharmacokinetic (PK) profile, and preliminary antitumor activity of SPR1020 monotherapy in this population.
The study consists of two parts: Phase I component (dose escalation and backfill) and Phase II component (dose expansion). The primary objectives of the Phase I part are to investigate the safety, tolerability, and PK profile of SPR1020 and to determine the Recommended Phase II Dose (RP2D) and/or the Maximum Tolerated Dose (MTD), if attainable. The Phase II part will be initiated once the RP2D and/or MTD is established in the Phase I part.
As a new-generation, highly selective PARP1 inhibitor, SPR1020 demonstrates a competitive clinical benefit-risk profile, combining potential intracranial activity with a differentiated safety profile. By leveraging a "synthetic lethality" mechanism, SPR1020 is expected to demonstrate significant efficacy against tumors harboring BRCA mutations or homologous recombination repair (HRR) pathway gene alterations (e.g., breast cancer, prostate cancer). Owing to its high selectivity for PARP1 over PARP2, SPR1020 may circumvent the hematological toxicities associated with PARP2 inhibition by first-generation pan-PARP inhibitors (e.g., olaparib), potentially resulting in an improved safety profile. This enhanced safety may provide greater flexibility for use in combination therapies. Furthermore, SPR1020's ability to penetrate the blood-brain barrier could offer a new treatment option for patients with advanced disease and brain metastases, addressing a high unmet medical need in this population with limited therapeutic choices. Preclinical data support this differentiated profile in terms of both efficacy and toxicity.
Hypothesis: SPR1020 represents a novel anticancer therapeutic with the potential for enhanced efficacy and an improved safety profile. The overall assessment indicates that its clinical benefits outweigh the potential risks.
This study has been approved by the IEC and adheres to the principles of the Declaration of Helsinki.
Male or female subjets ≥ 18 years old.
Phase I Dose-Escalation Part: Patients with histologically or cytologically confirmed, surgically unresectable, locally advanced or metastatic malignant solid tumors, who have experienced failure of standard therapy, or for whom no standard therapy exists, or who are intolerant to standard therapy. (Priority will be given to enrolling patients with breast, ovarian, prostate, or pancreatic cancer harboring homologous recombination deficiency (HRD)-related gene mutations such as BRCA1/2, PALB2, RAD51C/D).
Histologically or cytologically confirmed HER2-negative (HR+/HER2- or triple-negative) advanced or metastatic breast cancer.
Presence of a predicted loss-of-function BRCA1/2 mutation in germline or tumor tissue.
Have received systemic anti-tumor therapy (including chemotherapy, biotherapy, endocrine therapy, immunotherapy, etc.) within 4 weeks prior to the first dose of the investigational product, with the following specifics: mitomycin and nitrosoureas within 6 weeks from the last dose; oral fluorouracil drugs (such as tegafur and capecitabine) within 2 weeks from the last dose; small molecule targeted agents within 2 weeks or 5 half-lives from the last dose, whichever is shorter; have received any herbal or botanical products with purported anti-tumor effects within 2 weeks prior to the first dose of the investigational product.
Have received radiotherapy (with the exception of palliative radiotherapy) within 3 weeks prior to the initiation of study treatment, or have a history of radiation pneumonitis. Note: With the exception of a history of radiation pneumonitis, subjects must have recovered from all radiation-related toxicities.
Have received other unapproved investigational drugs within 4 weeks prior to the first dose of the investigational product, or within 5 half-lives of the other drug(s), whichever is shorter.
Have undergone major organ surgery (excluding Puncture Biopsy) within 4 weeks prior to the first dose of the investigational product, or have experienced significant trauma, or require elective surgery during the trial period.
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Treatment groupsSee each treatment group below.