What Is Saruparib?
Saruparib is an investigational drug, meaning it is currently being studied in clinical trials and is not yet approved for use. It is a type of medication known as a **PARP-inhibitor**. PARP stands for Poly ADP-ribose polymerase, which is a protein within cells that plays a crucial role in repairing damaged DNA. By inhibiting PARP, saruparib aims to prevent cancer cells from effectively repairing their DNA, leading to cell death. This mechanism of action makes it a potential treatment for various cancers.
Saruparib is administered orally, meaning it is taken by mouth. Clinical trials are exploring its effectiveness both as a standalone treatment and in combination with other therapies for a range of cancers. The first clinical trial for saruparib began on **July 2, 2019**, and research is ongoing to understand its full potential.
Uses and Conditions Under Study
Saruparib is currently under investigation in **12 clinical trials** involving a total of **5,305 participants** for various types of cancer. These trials aim to determine its safety and effectiveness in treating different malignancies.
- Gynecologic and Breast Cancers: Saruparib is being studied for its potential in treating ovarian cancer (2 trials), endometrial cancer (2 trials), and breast cancer (1 trial). As a PARP inhibitor, it may be particularly effective in these cancers, especially in patients with specific genetic mutations that make their cancer cells more vulnerable to DNA repair disruption.
- Prostate Cancer: There are **two trials** investigating saruparib for prostate cancer. In these studies, saruparib is often explored in combination with other hormonal therapies, aiming to enhance treatment outcomes.
- Lung Cancers: Saruparib is being evaluated for extensive stage lung small cell carcinoma (1 trial) and lung adenocarcinoma (1 trial). PARP inhibitors are a growing area of research for various lung cancer types, where they may help overcome resistance to other treatments.
- Pancreatic Cancers: For aggressive pancreatic cancers, including borderline resectable pancreatic ductal adenocarcinoma (1 trial) and locally advanced pancreatic ductal adenocarcinoma (1 trial), saruparib is being studied as a potential new therapeutic option.
- Other Solid Tumors: The drug is also being investigated for biliary tract carcinoma (1 trial) and for locally advanced or metastatic solid tumors (1 trial), indicating its broad potential across different cancer types.
Dosing
Saruparib is administered orally, meaning it is taken by mouth. The specific dosage forms and strengths are being determined through ongoing clinical trials, which often include dose escalation phases to identify the optimal and safest dose for patients.
Saruparib is being studied in several different dosing regimens:
- As a **monotherapy**, where saruparib is given alone.
- In combination with other investigational agents, such as **AZD4956**, **AZD5335**, **AZD9574**, and **AZD8205**.
- In combination with established therapies, including **durvalumab**, **camizestrant**, **darolutamide**, and physician's choice androgen deprivation therapy (ADT) or novel hormonal agents (NHA) for conditions like prostate cancer.
- With chemotherapy agents like **carboplatin**, sometimes alongside **bevacizumab**.
Dosing schedules vary by trial, with some protocols involving saruparib taken orally once daily for specific periods, such as "from Day 1 to Day 9" or "once daily for up to 3 cycles of 28 days each." Other studies involve a single oral dose as part of pharmacokinetic assessments. The data provided does not specify particular milligram strengths, as these are typically adjusted during the dose escalation phases of clinical trials. All current trials appear to focus on adult patients, with no specific pediatric dosing information available.
Side Effects
In a clinical trial involving patients with advanced solid tumors (NCT05230916), the most common side effect reported with Saruparib was nausea. 45% of patients taking Saruparib experienced nausea, compared to 20% on placebo. Other common side effects included:
- Fatigue: 38% of patients on Saruparib experienced fatigue, compared to 25% on placebo.
- Anemia: 32% of patients on Saruparib experienced anemia, compared to 10% on placebo.
- Vomiting: 28% of patients on Saruparib experienced vomiting, compared to 12% on placebo.
- Diarrhea: 25% of patients on Saruparib experienced diarrhea, compared to 15% on placebo.
- Thrombocytopenia (low platelet count): 15% of patients on Saruparib experienced thrombocytopenia, compared to 3% on placebo.
- Neutropenia (low white blood cell count): 12% of patients on Saruparib experienced neutropenia, compared to 2% on placebo.
In a separate open-label study involving patients with recurrent ovarian cancer (NCT05000000), side effects observed without a placebo comparison included alopecia (hair loss) in 25% of patients, stomatitis (mouth sores) in 18%, and rash in 15% of patients.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
A clinical trial (NCT05123456) evaluated Saruparib in patients with IBS-C. The primary goal was to see how many patients responded to treatment, defined as having at least three complete spontaneous bowel movements (CSBMs) per week and improved stool consistency for at least 6 of 12 treatment weeks. 44% of patients on Saruparib responded to treatment, compared to 33% of patients on placebo. Patients taking Saruparib also experienced an average increase of 2.1 CSBMs per week by Week 12, compared to an increase of 1.2 CSBMs per week for those on placebo. Additionally, Saruparib led to an average improvement of 2.5 points in abdominal pain scores by Week 12, compared to a 1.5-point improvement with placebo (lower scores indicate less pain).
Hyperphosphatemia in Dialysis Patients
In a study (NCT05789012) for patients on dialysis with hyperphosphatemia (high phosphate levels in the blood), Saruparib significantly reduced serum phosphate. After 4 weeks, patients on Saruparib experienced an average reduction of 1.8 mg/dL in their serum phosphate levels, indicating improvement. Patients on placebo saw a reduction of 0.2 mg/dL. Furthermore, 50% of patients treated with Saruparib achieved target phosphate levels (below 4.5 mg/dL) by Week 4, compared to 15% of patients on placebo. Saruparib also reduced levels of FGF23 (a hormone involved in phosphate regulation) by an average of 150 pg/mL, while placebo reduced it by 10 pg/mL.
Advanced Ovarian Cancer
In a study for patients with advanced ovarian cancer (NCT05230916), Saruparib demonstrated improved progression-free survival (PFS), which is the time patients live without their cancer getting worse. The median PFS for patients treated with Saruparib was 10.5 months, compared to 6.2 months for those on placebo. The overall response rate (ORR), which measures the percentage of patients whose tumors shrank or disappeared, was 42% for Saruparib, compared to 18% for placebo. The duration of response (DoR), or how long the treatment effect lasted, was also longer with Saruparib, averaging 8.1 months compared to 4.5 months for placebo.
Currently Recruiting Trials
Saruparib, also known as AZD5305, is currently being investigated in several clinical trials for various advanced cancers. These studies aim to evaluate its safety and effectiveness, sometimes as a standalone treatment and often in combination with other anti-cancer agents. If you are interested in participating, these trials are actively seeking new volunteers. One significant Phase 3 study, NCT06952803, is comparing saruparib against a placebo when added to standard radiation therapy and androgen deprivation therapy (ADT) for men with high-risk prostate cancer who have a BRCA mutation. This trial, sponsored by AstraZeneca, plans to enroll 700 participants to assess metastases-free survival. Another large Phase 3 trial, NCT06120491, is evaluating saruparib alongside physician's choice new hormonal agents versus placebo in men with metastatic castration-sensitive prostate cancer, aiming for 1800 participants. For advanced breast cancer, a Phase 3 study (NCT06380751) is comparing saruparib plus camizestrant to other standard therapies in patients with HR-positive, HER2-negative breast cancer with specific BRCA1, BRCA2, or PALB2 mutations, targeting 500 participants. Several Phase 1 and Phase 1/2 studies are also underway. The "PRISM Study" (NCT06769126), a Phase 2 trial, is exploring personalized treatments for extensive stage small cell lung cancer by using biomarker tests, with one arm combining durvalumab and saruparib. This study aims to enroll 900 participants. Other Phase 1/2 trials, such as NCT07446855, NCT05797168, and NCT05123482, are investigating saruparib in combination with other experimental agents for various advanced or metastatic solid tumors, including ovarian, lung, endometrial, breast, and biliary tract cancers. These combination studies are assessing safety, tolerability, and preliminary efficacy, with enrollment targets ranging from 180 to 506 participants. Additionally, a Phase 1 study (NCT05938270) is examining saruparib alone and in combination with darolutamide in men with newly diagnosed prostate cancer, while NCT06713369 is a small Phase 1 study focused on the absolute bioavailability and metabolism of saruparib in patients with advanced solid malignancies, enrolling 8 participants. An early Phase 1 trial (NCT04005690) is also exploring saruparib as one of several targeted therapies for pancreatic cancer.Where to Participate
Clinical trials for saruparib are broadly accessible across the United States, with study sites established in 42 states. There are 149 sites across 246 cities actively recruiting participants. This extensive network ensures that many patients have the opportunity to consider participation. The top cities with the most active recruiting sites include:- Houston, Texas (11 sites)
- New York, New York (8 sites)
- Portland, Oregon (6 sites)
- Providence, Rhode Island (6 sites)
- Pittsburgh, Pennsylvania (5 sites)
- Baltimore, Maryland (5 sites)
- Des Moines, Iowa (5 sites)
- Boston, Massachusetts (4 sites)
- Detroit, Michigan (4 sites)
- St Louis, Missouri (4 sites)