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

Recruiting at 1 trial location

Overseen By Paula Bradshaw

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

Trial Summary

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.

What data supports the effectiveness of the drugs N-803, Tislelizumab, and Docetaxel for treating non-small cell lung cancer?

Research shows that Tislelizumab, when compared to Docetaxel, improved the quality of life and health status of patients with advanced non-small cell lung cancer. Additionally, treatments similar to Tislelizumab, like other PD-1/PD-L1 inhibitors, have shown promising results in improving survival rates in patients with this type of cancer. ^{1 2 3 4 5}

Is the combination of N-803, Tislelizumab, and Docetaxel safe for humans?

Tislelizumab and Docetaxel have been studied for safety in patients with non-small cell lung cancer, showing that Tislelizumab can improve quality of life compared to Docetaxel, which has a risk of causing myelotoxicity (a decrease in bone marrow activity). ^{1 2 6 7 8}

What makes the combination of N-803, Tislelizumab, and Docetaxel unique for treating non-small cell lung cancer?

This treatment combines N-803, an immune system booster, with Tislelizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, and Docetaxel, a chemotherapy drug. This combination aims to enhance the body's immune response while directly targeting cancer cells, offering a potentially more effective approach than using these drugs individually. ^{3 4 8 9 10}

What is the purpose of this trial?

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) versus docetaxel monotherapy (control arm). Enrolled participants will be randomized 2:1 to treatment in the experimental arm or the control arm. Participant randomization will be stratified by geographical region (North America vs Europe vs ASIA vs Other), NSCLC histology (squamous vs nonsquamous), and actionable genomic alteration (AGA); (epidermal growth factor receptor \[EGFR\]/anaplastic lymphoma kinase \[ALK\] vs OTHER AGA vs No AGA).

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. United States 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

The effects of tislelizumab treatment on the health-related quality of life of patients with advanced non-small cell lung cancer. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. [2022]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Addition of Anti-PD1 to Chemotherapy in Treatment of Non-Small Cell Lung Cancer. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Anti-PD-1/anti-PD-L1 immunotherapy versus docetaxel for previously treated advanced non-small cell lung cancer: a systematic review and meta-analysis of randomised clinical trials. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Updated Efficacy Analysis Including Secondary Population Results for OAK: A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non-Small Cell Lung Cancer. [2022]

7. England 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Randomized phase III study of 3-weekly versus weekly docetaxel in pretreated advanced non-small-cell lung cancer: a Spanish Lung Cancer Group trial. [2022]

9. Greece pubmed.ncbi.nlm.nih.gov

Interstitial lung disease associated with docetaxel in patients with advanced non-small cell lung cancer. [2018]

10. England 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. [2022]