An Open-label, First-in-Human, Dose-Escalation and Dose-Expansion Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SPR1020 in Patients With Advanced Solid Tumors

NCT07359066 | Recruiting Phase 1

• 1 other identifier: SPR1020-S-001
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Advanced Solid Tumors; PARP Inhibitor

Keywords

SPR1020

Outcome Measures

Primary Outcomes (3)

• DLT/MTD

  Incidence and characteristics of Dose-Limiting Toxicity (DLT) to determine the Maximum Tolerated Dose (MTD).

  Within 24 days after the first dose (including 3 days of Cycle 0 and 21 days of Cycle 1)

• RP2D

  Recommended Phase II Dose (RP2D) of SPR1020, as the dose for efficacy study in Phase II, will be the dose with promising clinical responses observed in the patients, and well tolerated by patients.

  From the first dose until disease progresses or end of treatment for other reasons，up to 1 year

• Incidence and characteristics of AEs and SAEs (according to NCI CTCAE 5.0)

  Incidence and characteristics of Adverse Events (AEs) and Serious Adverse Events (SAEs) throughout the study period, were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0.

  All AEs/SAEs (including irAEs/AESIs) will be collected from first dose until 30 days after the last dose, or until new anti-tumor therapy begins，up to 1 year

Secondary Outcomes (15)

• ORR

  From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first，up to 1 year

• DCR

  From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first，up to 1 year

• DOR

  From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first，up to 1 year

• PFS

  From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first，up to 1 year

• OS

  From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first，up to 1 year

Study Arms (6)

25mg/day

EXPERIMENTAL

Drug: SRP1020

50mg/day

EXPERIMENTAL

Drug: SRP1020

100mg/day

EXPERIMENTAL

Drug: SRP1020

150mg/day

EXPERIMENTAL

Drug: SRP1020

200mg/day

EXPERIMENTAL

Drug: SRP1020

250mg/day

EXPERIMENTAL

Drug: SRP1020

Interventions

SRP1020 DRUG

SPR1020 is administered orally. The dosing frequency is once daily (QD). Each treatment cycle is 21 days.

100mg/day; 150mg/day; 200mg/day; 250mg/day; 25mg/day; 50mg/day

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Phase I Dose Backfill Portion: Patients with HER2-negative breast cancer (BC), advanced epithelial ovarian cancer (OC)/fallopian tube cancer (FTC)/primary peritoneal cancer (PPC), or castration-resistant prostate cancer (CRPC), who have a documented pathogenic or likely pathogenic BRCA mutation (BRCAm, germline or somatic) as detected by a local or central laboratory, and who have experienced failure of at least one prior line of standard anticancer therapy (refer to the protocol section for the Phase II dose expansion for specific standard therapy requirements); Or patients with other tumor types harboring homologous recombination deficiency (HRD) related gene mutations (including but not limited to esophageal cancer, small cell lung cancer, or pancreatic cancer) who have experienced failure of at least one prior line of standard therapy.
• Phase II Dose Expansion Study: Allows prior treatment with a pan-PARP inhibitor (no more than 1 type). Specific requirements for each cohort are as follows:
• Cohort 1: Breast Cancer (BC):
• 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.
• Received at least \> 1 line of systemic therapy for advanced disease (must have received at least one line of chemotherapy; if HR+, must have received endocrine therapy), with recent radiological confirmation of disease progression.
• Cohort 2: Ovarian Cancer (OC):
• Histologically confirmed high-grade serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
• Presence of a predicted loss-of-function BRCA1/2 mutation in germline or tumor tissue.
• Received at least \> 1 line of systemic therapy for advanced disease (must have received at least one platinum-based chemotherapy regimen for advanced disease), with recent radiological confirmation of disease progression.
• Subjects must have a response duration of ≥ 6 months after the last platinum-based chemotherapy (platinum-sensitive population).
• Cohort 3: Prostate Cancer (PC):
• Histologically or cytologically confirmed prostatic adenocarcinoma, which has progressed to the castration-resistant stage.

You may not qualify if:

• 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.
• Prior treatment with a PARP1 inhibitor. Note: For subjects enrolling in the dose-escalation phase, enrollment may be considered following discussion with and agreement from the sponsor's medical representative.
• Have received or are anticipated to require long-term systemic glucocorticoid therapy (prednisone \>10 mg/day or equivalent) or other immunosuppressive therapy within 14 days prior to the first dose of the investigational product. The following are exceptions: topical, intra-articular, intranasal, and inhaled corticosteroids; corticosteroid administration as premedication for contrast-enhanced imaging studies to prevent allergic reactions; short-term (≤ 7 days) use of corticosteroids for the prevention or treatment of non-autoimmune allergic conditions; and glucocorticoids used during the treatment stage for castration-resistant prostate cancer (CRPC).
• Have used immunomodulatory agents, including but not limited to thymic peptides, interleukin-2 (IL-2), interferon, etc., within 14 days prior to the first dose of the investigational product.
• Have received a live or attenuated live vaccine within 4 weeks prior to the first dose of the investigational product. Inactivated vaccines are permitted.
• Have used within 7 days prior to the first dose of the investigational product or require concomitant use during the study treatment period of medications, herbal supplements, or foods known to be strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (refer to Appendix 4 a summary list of common CYP3A4 enzyme inducers and inhibitors).
• Have a prior history of allogeneic bone marrow transplantation or solid organ transplantation.
• Patients with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or presenting with features suggestive of MDS/AML.
• Have difficulty swallowing oral medications, or have malabsorption syndrome or any other poorly controlled gastrointestinal disease that may affect bioavailability.
• Patients with central nervous system (CNS) metastases meeting any of the following criteria: (a) requiring local therapy (surgery, radiotherapy, or other); (b) CNS metastases requiring or currently being treated with corticosteroids at a dose \>10 mg prednisone or equivalent; (c) unstable CNS metastases or a stability duration of less than 14 days after the last treatment prior to enrollment; (d) presence of spinal cord compression or leptomeningeal metastasis.
• Presence of severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to the first dose (including tuberculosis infection).
• Have a known history of a positive human immunodeficiency virus (HIV) test or acquired immunodeficiency syndrome (AIDS).

Sponsors & Collaborators

• Shanghai SciBrunch Therapeutics Co., Ltd.: lead

Study Sites (2)

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

NOT YET RECRUITING

The Affiliated Tumor Hospital of Harbin Medical University

Harbin, Heilongjiang, 150081, China

RECRUITING

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2025
• First Posted: January 22, 2026
• Study Start: January 8, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: February 5, 2026

Record last verified: 2026-01

Locations

CN (2)