N-803 + Tislelizumab + Docetaxel for Non-Small Cell Lung Cancer

Recruiting at 9 trial locations

Overseen By Tamra Madenwald

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ImmunityBio, Inc.

Must be taking: Anti-retroviral therapy

Must not be taking: CYP3A4 inhibitors, Immunosuppressants

Disqualifiers: Autoimmune disease, Hepatitis B/C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Varies by participant

460 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with stage IV non-small cell lung cancer (NSCLC) who no longer respond to certain immune therapies. Researchers aim to determine if adding two drugs, N-803 (an experimental treatment) and tislelizumab (an immune checkpoint inhibitor), to the standard chemotherapy drug docetaxel is more effective than using docetaxel alone. Individuals with specific genetic changes in their cancer, who have undergone certain treatments, and who have developed resistance to some immune therapies may be suitable for this study. Participants should be able to attend regular study visits and adhere to study guidelines. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on CYP3A4 inhibitors or have been on systemic steroids or immunosuppressive medication within 3 days before the study starts.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that the combination of N-803, tislelizumab, and docetaxel has promising safety results. Research indicates that patients tolerated this combination well, with manageable side effects. Specifically, tislelizumab has provided significant and lasting benefits in overall survival compared to docetaxel alone for patients with advanced non-small cell lung cancer. This suggests the treatment is reasonably safe, having been tested in patients with similar conditions. While side effects can occur, the study aims to ensure safety and improve outcomes. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for non-small cell lung cancer?

Researchers are excited about the combination of N-803, Tislelizumab, and Docetaxel for treating non-small cell lung cancer because it builds on the standard chemotherapy approach in innovative ways. Unlike traditional treatments that primarily focus on attacking cancer cells directly, this combination leverages the immune system to enhance its cancer-fighting ability. N-803 is an immune-modulating agent that boosts the activity of certain immune cells, while Tislelizumab is a checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. The inclusion of Docetaxel, a well-known chemotherapy drug, rounds out the regimen by directly targeting and killing cancer cells. This multifaceted approach could potentially offer a more effective and comprehensive treatment option for patients.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

This trial will compare two treatment regimens for non-small cell lung cancer (NSCLC). The experimental arm combines N-803, tislelizumab, and docetaxel. Studies have shown that this combination can improve outcomes for patients with NSCLC. Research suggests that N-803 boosts the immune system, increasing white blood cell levels and helping patients live longer. Tislelizumab, when combined with docetaxel, has been found to be more effective than docetaxel alone. This combination treatment shows promise for patients who haven't responded well to other treatments. Meanwhile, the control arm will receive docetaxel alone. Although the results are encouraging, ongoing studies are needed to confirm these benefits. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with stage IV Non-Small Cell Lung Cancer (NSCLC) who've had resistance to certain immune therapies. They must have specific genetic alterations in their cancer and may have received targeted treatments like Osimertinib. Good physical health, as measured by ECOG status, is required.

Inclusion Criteria

My cancer has a specific genetic alteration.

Participants must be able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines

Participants must have measurable tumor lesions according to RECIST v1.1 at Baseline day 1

Exclusion Criteria

I haven't taken autoimmune disease treatment for the last 6 months.

I do not have an active hepatitis B or C infection.

Participants assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol are excluded

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either N-803 plus tislelizumab and docetaxel or docetaxel monotherapy in repeated 3-week cycles

Varies by participant

Every 3 weeks (± 3 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• N-803
• Tislelizumab

Trial Overview The study compares a combination of N-803 plus tislelizumab and docetaxel against docetaxel alone in advanced NSCLC patients. Participants are randomly assigned to either the experimental group or control group at a ratio of 2:1, considering factors like region, cancer type, and genetic changes.

How Is the Trial Designed?

Group I: Experimental Arm Experimental Treatment 3 Interventions

The treatment regimen for the experimental arm will be as follows. Agents are to be administered in the order listed (eg, on day 1 experimental arm \[cycles 1 and 2\], administer N-803, followed tislelizumab and then followed by docetaxel).

Group II: Control Arm Experimental Treatment 1 Intervention

The control arm treatment regimen will consist of repeated 3-week cycles with a ± 3-day window for each visit of Docetaxel 75 mg/m2 IV.

Who Is Running the Clinical Trial?

ImmunityBio, Inc.

Lead Sponsor

Trials

75

Recruited

5,000+

Richard Adcock

ImmunityBio, Inc.

Chief Executive Officer since 2024

Information not available

Dr. Patrick Soon-Shiong

ImmunityBio, Inc.

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In the phase 3 RATIONALE-303 trial involving 805 patients with advanced non-small cell lung cancer (NSCLC), tislelizumab demonstrated a significant improvement in overall survival (OS) compared to docetaxel, with median OS of 17.2 months versus 11.9 months, respectively.

Tislelizumab showed consistent efficacy across different PD-L1 expression levels, and exploratory analyses suggested that certain genetic mutations (NOTCH1-4) may enhance its effectiveness, while no new safety concerns were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab Versus Docetaxel in Patients With Previously Treated Advanced NSCLC (RATIONALE-303): A Phase 3, Open-Label, Randomized Controlled Trial. Zhou, C., Huang, D., Fan, Y., et al.[2023]

In a phase 3 trial involving 423 patients with untreated stage IV or recurrent non-small-cell lung cancer (NSCLC) and PD-L1 expression of 5% or more, nivolumab did not show a significant improvement in progression-free survival compared to chemotherapy, with median times of 4.2 months versus 5.9 months, respectively.

Nivolumab demonstrated a better safety profile than chemotherapy, with 71% of patients experiencing treatment-related adverse events compared to 92% in the chemotherapy group, and significantly fewer severe adverse events (grade 3 or 4) at 18% versus 51%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. Carbone, DP., Reck, M., Paz-Ares, L., et al.[2022]

Tislelizumab, an anti-PD-1 monoclonal antibody, shows improved progression-free survival and objective response rates in treating non-small cell lung cancer (NSCLC), especially when combined with chemotherapy, based on a review of four randomized controlled trials involving 1565 patients.

While tislelizumab is generally effective, it is associated with treatment-emergent adverse events, including significant hematologic issues and immune-mediated effects like hypothyroidism and pneumonitis, with a mortality rate from these events ranging from 3.2% to 4.2%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of tislelizumab, alone or in combination with chemotherapy, for the treatment of non-small cell lung cancer: a systematic review of clinical trials. Daei Sorkhabi, A., ZareDini, M., Fazlollahi, A., et al.[2023]

In a phase 2 trial involving 287 patients with previously treated advanced non-small-cell lung cancer (NSCLC), atezolizumab significantly improved overall survival (12.6 months) compared to docetaxel (9.7 months), with a hazard ratio of 0.73, indicating a 27% reduction in the risk of death.

The efficacy of atezolizumab was found to correlate with PD-L1 expression levels on tumor cells and immune cells, suggesting that higher PD-L1 expression may predict better outcomes with this treatment, while atezolizumab also demonstrated a better safety profile with fewer severe adverse events compared to docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Fehrenbacher, L., Spira, A., Ballinger, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06745908

ResQ201A: Clinical Trial Of N-803 Plus TISLELIZUMAB ... This is a randomized, open-label, phase 3 clinical trial to compare the efficacy and safety of N-803 plus tislelizumab and docetaxel (experimental arm) ...

2. immunitybio.com immunitybio.com/immunitybios-anktiva-reverses-lymphopenia-and-extends-overall-survival-in-patients-with-advanced-non-small-cell-lung-cancer-resistant-to-checkpoint-therapy/

ImmunityBio's ANKTIVA® Reverses Lymphopenia and ... ImmunityBio's ANKTIVA® Reverses Lymphopenia and Extends Overall Survival in Patients With Advanced Non-Small Cell Lung Cancer Resistant to ...

3. clin.larvol.com clin.larvol.com/trial-detail/NCT06745908

ResQ201A: Clinical Trial Of N-803 Plus TISLELIZUMAB ... "Non-Small Cell Lung Cancer (NSCLC): ImmunityBio has launched ResQ201A, a randomized controlled trial (RCT), in the U.S., evaluating its IL-15 superagonist ...

4. withpower.com withpower.com/trial/phase-3-carcinoma-non-small-cell-lung-2025-13e70

N-803 + Tislelizumab + Docetaxel for Non-Small Cell Lung ... This is a randomized, open-label, phase 3 clinical trial to compare the efficacy and safety of N-803 plus tislelizumab and docetaxel (experimental arm) ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39091529/

Cost-effectiveness analysis of the tislelizumab versus ... This study aimed to evaluate the cost-effectiveness of tislelizumab compared to docetaxel from a Chinese healthcare system perspective.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36184068/

Tislelizumab Versus Docetaxel in Patients With Previously ... Tislelizumab was found to have a significantly improved and long-term clinical benefit in OS versus docetaxel in pretreated patients with advanced NSCLC.