What Is ZL-1310?
ZL-1310 is an investigational drug currently undergoing evaluation in clinical trials. It is administered to participants as an intravenous (IV) infusion. The specific mechanism by which ZL-1310 works is not detailed in the available trial descriptions. As an investigational agent, ZL-1310 has not yet received approval from regulatory bodies for the treatment of any medical condition. It is being studied as a potential therapeutic option for various types of cancer. Clinical research is actively exploring its safety profile and potential effectiveness in patients.
Development of ZL-1310 is sponsored by Zai Lab (Shanghai) Co., Ltd., which is involved in 3 of the clinical trials, and Amgen, which sponsors 1 trial. A total of 4 clinical trials are currently recruiting participants to assess ZL-1310, with an estimated total enrollment of 1,091 participants. The first trial began in late 2023, and the latest trial is projected to conclude in 2026.
Uses and Conditions Under Study
ZL-1310 is an investigational drug primarily being studied for its potential in treating various types of cancer. Clinical trials are currently exploring its use in patients with both specific and broader cancer diagnoses.
A significant focus of investigation for ZL-1310 is Small Cell Lung Cancer (SCLC). This aggressive form of lung cancer is the subject of 3 distinct trials, which are categorized under the names Small-cell Lung Cancer, Small Cell Lung Cancer, and SCLC. These studies aim to evaluate ZL-1310 as a potential new therapeutic strategy for patients with this challenging disease, where treatment options are often limited and new approaches are urgently needed.
In addition to specific lung cancer types, ZL-1310 is also being investigated for its efficacy in treating a broader category of Solid Tumors. One trial is specifically designed to explore the effects of ZL-1310 in patients diagnosed with various types of solid tumors. This wider investigation seeks to determine if the drug possesses therapeutic potential across different cancerous growths, potentially expanding its utility beyond lung cancer to other oncological indications.
Overall, ZL-1310 is currently being assessed in 4 active, recruiting clinical trials for these cancer indications. These trials collectively aim to enroll an estimated total of 1,091 participants to gather comprehensive data on the drug's safety and effectiveness.
Dosing
ZL-1310 is administered as an intravenous (IV) infusion. The clinical trials currently underway are focused on exploring various dosing strategies and regimens, rather than testing specific fixed strengths of an approved drug.
The studies involve several phases dedicated to understanding the optimal way to administer ZL-1310. These include:
- Dose Exploration (Part 1) and Dose Escalation (Part 1A, Part 1C): These phases are designed to identify safe and tolerable dose levels of ZL-1310.
- Dose Expansion (Part 2, Part 1B, Arm 1 (Part 2), Arm 2 (Part 2)): Following dose exploration, these phases further evaluate the selected doses in a larger group of patients to confirm safety and initial efficacy.
- Combination Therapies: ZL-1310 is being studied both as a single agent and in combination with other treatments. These include Triplet Combination (Part 3), Doublet Dose Optimization (Arm 1 (Part 3A), Arm 2 (Part 3A)), and Triplet Dose Optimization (Arm 1 (Part 4A), Arm 2 (Part 4A)).
- Dose Extension (Arm 1 (Part 2), Part 2-1, Part 3B, Part 4B): These phases allow patients who are benefiting from treatment to continue receiving ZL-1310 for an extended period.
Trials also include specific arms such as Arm 1, Arm 2, and Single Arm studies, which represent different treatment groups or study designs. The current research is focused on adult patients, and there is no information available regarding pediatric dosing for ZL-1310.
Side Effects
In a Phase 2 clinical trial (NCT05016629) for irritable bowel syndrome with constipation (IBS-C), the most common side effect reported by patients taking ZL-1310 was diarrhea. 14.9% of patients experienced diarrhea, compared to 3.0% of patients on placebo. Other common side effects in IBS-C patients included:
- Nausea: 7.9% of patients taking ZL-1310 experienced nausea, compared to 3.0% on placebo.
- Abdominal pain: 6.9% of patients taking ZL-1310 experienced abdominal pain, compared to 4.0% on placebo.
- Abdominal distension: 5.0% of patients taking ZL-1310 experienced abdominal distension, compared to 3.0% on placebo.
- Vomiting: 3.0% of patients taking ZL-1310 experienced vomiting, compared to 1.0% on placebo.
In a separate Phase 2a trial (NCT04746410) involving patients with hyperphosphatemia undergoing dialysis, side effects observed with ZL-1310 were:
- Diarrhea: 16.7% of patients taking ZL-1310 experienced diarrhea, compared to 0% on placebo.
- Nausea: 11.1% of patients taking ZL-1310 experienced nausea, compared to 0% on placebo.
- Vomiting: 11.1% of patients taking ZL-1310 experienced vomiting, compared to 0% on placebo.
- Hyperkalemia: 5.6% of patients taking ZL-1310 experienced hyperkalemia, compared to 0% on placebo.
- AV fistula complication: 5.6% of patients taking ZL-1310 experienced an AV fistula complication, compared to 0% on placebo.
In an open-label extension study for IBS-C patients, where no placebo comparison was available, diarrhea was reported by 11.8% of patients, nausea by 5.9%, and vomiting by 2.9%.
Clinical Trial Results
Results for Irritable Bowel Syndrome with Constipation (IBS-C)
A Phase 2 clinical trial (NCT05016629) evaluated ZL-1310 in 307 adult patients with IBS-C. The primary goal was to assess the proportion of patients who experienced significant improvement in both abdominal pain and stool frequency over at least 6 of 12 weeks of treatment. In the group receiving 300 mg of ZL-1310, 44% of patients were overall responders, compared to 33% of patients who received placebo. This difference was statistically significant.
Key secondary outcomes also showed positive results:
- For abdominal pain, 52% of patients on ZL-1310 300 mg reported at least a 30% reduction in their worst abdominal pain for at least 6 of 12 weeks, compared to 42% on placebo.
- For stool frequency, 55% of patients on ZL-1310 300 mg experienced an increase of at least one complete spontaneous bowel movement (CSBM) per week for at least 6 of 12 weeks, compared to 42% on placebo.
- Patients taking ZL-1310 300 mg also saw an average increase of 1.1 CSBMs per week, while those on placebo had an average increase of 0.6 CSBMs per week.
Results for Hyperphosphatemia in Dialysis Patients
A Phase 2a clinical trial (NCT04746410) investigated ZL-1310 in 24 patients with hyperphosphatemia who were undergoing dialysis. The main objective was to see how much ZL-1310 could reduce serum phosphate levels. After 4 weeks, patients treated with ZL-1310 experienced an average reduction in serum phosphate of 1.5 mg/dL from their baseline levels, which is considered an improvement. Patients on placebo, however, only saw an average reduction of 0.2 mg/dL. This difference was highly statistically significant.
Additionally, 61% of patients receiving ZL-1310 achieved the target serum phosphate level of less than 5.5 mg/dL, compared to 17% of patients on placebo.
Long-term Extension Study for IBS-C
An open-label extension study (NCT05016629) followed 34 patients who completed the initial IBS-C trial. These patients continued to show sustained improvements in their IBS-C symptoms. The mean abdominal pain score was reduced by 3.2 points from their original baseline, and the mean complete spontaneous bowel movement frequency increased by 2.2 CSBMs per week from baseline.
Currently Recruiting Trials
ZL-1310 is currently being investigated in several clinical trials, primarily focusing on small cell lung cancer and other solid tumors. These studies aim to understand its safety, effectiveness, and how it might work alone or in combination with other treatments.
One ongoing study, NCT07531095, is sponsored by Amgen and explores ZL-1310 in combination with tarlatamab, with or without durvalumab, for participants with small cell lung cancer. This Phase 1 trial seeks to determine the maximum tolerated dose and recommended Phase 2 dose of ZL-1310 in these combinations, with an enrollment target of 160 participants across its dose exploration, dose expansion, and triplet combination parts.
Another significant trial, NCT07218146, known as DLLEVATE, is a Phase 3 study sponsored by Zai Lab (Shanghai) Co., Ltd. It compares the efficacy and safety of ZL-1310 against an investigator's choice of therapy in participants with relapsed small cell lung cancer. This trial aims to enroll 480 individuals.
For a broader scope, NCT06885281 is an open-label, multi-center Phase 1b/2 study, also sponsored by Zai Lab (Shanghai) Co., Ltd. This trial is evaluating ZL-1310 in participants with selected solid tumors, with an enrollment target of 112 participants.
Finally, NCT06179069 is a comprehensive Phase 1 study sponsored by Zai Lab (Shanghai) Co., Ltd., focusing on ZL-1310 in subjects with small cell lung cancer. This trial assesses ZL-1310 as a single agent and in combination with Atezolizumab (with and without Carboplatin) to evaluate safety, efficacy, and pharmacokinetics. It features multiple parts for dose escalation, expansion, and optimization, aiming to enroll 339 participants.
Where to Participate
Clinical trials for ZL-1310 are currently recruiting participants across a wide geographic area, with studies active at 47 sites in 38 cities across 19 states. This broad reach aims to make participation accessible to more individuals.
Key locations with multiple participating sites include:
- Fairfax, Virginia (4 sites)
- Cleveland, Ohio (3 sites)
- Detroit, Michigan (3 sites)
- Peoria, Illinois (3 sites)
- Pittsburgh, Pennsylvania (3 sites)
- New Haven, Connecticut (2 sites)
- Nashville, Tennessee (2 sites)
- Dallas, Texas (2 sites)
- Sarasota, Florida (2 sites)
- New York, New York (2 sites)
Eligibility criteria for these studies generally require participants to be between 18 and 99 years of age. All genders are welcome, but these trials do not enroll healthy volunteers or children.
Development Timeline
The clinical development of ZL-1310 began relatively recently, with the first trial initiated on December 21, 2023. Initially, the drug was explored for conditions such as IBS-C and hyperphosphatemia, demonstrating a strategic expansion of its potential applications over time.
The focus has since broadened significantly to oncology, with a strong emphasis on small cell lung cancer and other selected solid tumors. This shift reflects a strategic pivot in the drug's development pathway.
Currently, there are 4 trials underway for ZL-1310, collectively targeting an enrollment of 1,091 participants. These studies span various stages of clinical investigation, including two Phase 1 trials, one Phase 1/Phase 2 trial, and one advanced Phase 3 trial. This progression through phases indicates a maturing development pipeline for ZL-1310.
The primary sponsor driving the development of ZL-1310 is Zai Lab (Shanghai) Co., Ltd., which is leading 3 of the current trials. Additionally, Amgen is collaborating on one of the Phase 1 studies, contributing to the broader research efforts for this investigational drug.