CAB-AXL-ADC + PD-1 Inhibitor for Lung Cancer

Recruiting at 60 trial locations

Overseen By BioAtla Medical Affairs

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: BioAtla, Inc.

Disqualifiers: Cardiac disease, CNS metastasis, HIV, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

240 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of this study is to assess safety and efficacy of CAB-AXL-ADC in NSCLC

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug CAB-AXL-ADC + PD-1 Inhibitor for lung cancer?

Research shows that PD-1 inhibitors, which are part of this treatment, have been effective in treating advanced non-small cell lung cancer, especially when combined with other agents like chemotherapy or anti-angiogenic drugs. These combinations have improved survival rates and are approved for use in various settings, indicating potential effectiveness for the combination with CAB-AXL-ADC. ^{1 2 3 4 5}

What safety data exists for PD-1 inhibitors in lung cancer treatment?

PD-1 inhibitors, used in lung cancer treatment, can cause immune-related side effects like pneumonitis (lung inflammation), colitis (colon inflammation), and hepatitis (liver inflammation). These side effects are generally manageable, but in some cases, they can be severe and require stopping the treatment. ^{6 7 8 9 10}

How is the drug CAB-AXL-ADC + PD-1 Inhibitor unique for lung cancer treatment?

The drug CAB-AXL-ADC + PD-1 Inhibitor is unique because it combines a novel antibody-drug conjugate (CAB-AXL-ADC) with a PD-1 inhibitor, potentially enhancing the immune system's ability to target and destroy cancer cells, which differs from standard treatments that typically involve chemotherapy or single-agent immune checkpoint inhibitors. ^{1 3 5 11 12}

Eligibility Criteria

Adults over 18 with non-small cell lung cancer (NSCLC) who have measurable disease, are in good physical condition (ECOG status of 0 or 1), and expected to live at least three months. They must have proper blood, kidney, and liver function. Those with severe heart issues, prior specific cancer treatments, recent major surgery, uncontrolled brain metastasis, certain allergies or infections like HIV/hepatitis are excluded.

Inclusion Criteria

My kidneys are working well.

I am fully active or restricted in physically strenuous activity but can do light work.

Life expectancy of at least three months.

Exclusion Criteria

I do not have uncontrolled brain metastases.

I have never had a severe allergic reaction to antibody treatments.

I am not pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CAB-AXL-ADC (BA3011) alone or in combination with a PD-1 inhibitor

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CAB-AXL-ADC
• PD-1 inhibitor

Trial Overview The trial is testing the safety and effectiveness of a new drug called CAB-AXL-ADC for NSCLC patients. It's being compared against PD-1 inhibitors which are a type of immunotherapy that helps the immune system fight cancer cells.

Participant Groups

Group I: CAB-AXL-ADC (BA3011)+PD-1 inhibitor Experimental Treatment 2 Interventions

CAB-AXL-ADC (BA3011) with PD-1 inhibitor

Group II: CAB-AXL-ADC (BA3011) Experimental Treatment 1 Intervention

CAB-AXL-ADC (BA3011) alone

Who Is Running the Clinical Trial?

BioAtla, Inc.

Lead Sponsor

Trials

7

Recruited

1,500+

Findings from Research

Single-agent immune checkpoint inhibitors (ICIs) significantly improve overall survival in patients with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥50% compared to platinum-based chemotherapy, with a hazard ratio of 0.68 based on data from 2111 participants across six trials.

Double-agent ICIs also likely enhance overall survival in the same patient group, showing a hazard ratio of 0.72 from two trials involving 612 participants, although their effects on progression-free survival and quality of life remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer. Ferrara, R., Imbimbo, M., Malouf, R., et al.[2022]

In a review of 23 randomized controlled trials involving 15,797 patients, PD-1 inhibitors significantly improved overall survival (OS) by an average of 4.80 months compared to standard care, while PD-L1 inhibitors improved OS by 2.59 months.

PD-1 inhibitors were found to provide greater OS benefits than PD-L1 inhibitors, suggesting that PD-1 inhibitors may be the preferred choice for treating advanced non-small-cell lung cancer (NSCLC), especially in patients with varying PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relative and absolute benefit of programmed death receptor-1 vs programmed death ligand 1 therapy in advanced non-small-cell lung cancer: A systematic review and meta-analysis. Yi, K., Zhu, Q., Kuang, YK., et al.[2021]

Single-agent immune checkpoint inhibitors (ICIs) significantly improve overall survival in patients with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥50% compared to platinum-based chemotherapy, with a hazard ratio of 0.68 based on data from 2111 participants across six trials.

Double-agent ICI treatment also likely enhances overall survival in the same patient group, with a hazard ratio of 0.72 from 612 participants in two trials, although data on progression-free survival and quality of life are limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer. Ferrara, R., Imbimbo, M., Malouf, R., et al.[2022]

A study of 227 lung cancer patients revealed significant differences in the incidence of treatment-related adverse events (AEs) among various PD-1 inhibitors, with camrelizumab showing the highest rate of all-grade AEs at 62.96%, while toripalimab had the lowest at 9.52%.

The most common AEs varied by drug, with camrelizumab associated with capillary hemangioma and abnormal liver function, while nivolumab and pembrolizumab were linked to pneumonitis, indicating the need for tailored monitoring strategies based on the specific PD-1 inhibitor used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of different PD-1 inhibitors in lung cancer patients: a real-world study. Zheng, X., Tao, G., Sun, S., et al.[2022]

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

In a study of 56 patients with advanced non-small-cell lung cancer (NSCLC) and concurrent autoimmune disease (AID) treated with PD-1 or PD-L1 inhibitors, 55% experienced an AID flare or immune-related adverse event (irAE), but most were manageable and did not lead to treatment discontinuation.

The overall response rate to PD-(L)1 therapy in this population was 22%, indicating that while there are risks, the treatment can still be effective for patients with NSCLC and AID.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Programmed Death-1 Pathway Inhibitors Among Patients With Non-Small-Cell Lung Cancer and Preexisting Autoimmune Disorders. Leonardi, GC., Gainor, JF., Altan, M., et al.[2022]

In a study of 276 patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors, those who developed checkpoint inhibitor pneumonitis (CIP) had a significantly higher overall response rate (61.90% vs. 29.91%) and longer progression-free survival (PFS) (45.80 weeks vs. 21.15 weeks) compared to those without CIP.

Grade 1-2 pneumonitis was associated with increased efficacy of the inhibitors, while more severe grade 3-4 pneumonitis did not show this association, suggesting that milder forms of pneumonitis may indicate better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of immune-related pneumonitis with the efficacy of PD-1/PD-L1 inhibitors in non-small cell lung cancer. Cui, P., Huang, D., Wu, Z., et al.[2022]

Nivolumab was the first immune checkpoint inhibitor approved for non-small cell lung cancer (NSCLC) by the FDA, showing a survival advantage over the traditional treatment docetaxel in recurrent squamous NSCLC, which is known to be challenging to treat.

Several other immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway are in late-stage development, with ongoing research into their efficacy and the potential use of PD-L1 expression as a biomarker to identify patients who are most likely to benefit from these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Perspectives in Immunotherapy for Non-Small Cell Lung Cancer. Garon, EB.[2020]

Immune checkpoint inhibitors, such as ipilimumab and anti-PD-1 agents like nivolumab and pembrolizumab, work by enhancing the immune system's ability to fight non-small cell lung cancer (NSCLC), differing from traditional chemotherapy that targets tumor cells directly.

Preliminary evidence indicates that these inhibitors can be effective as standalone treatments or in combination with chemotherapy, highlighting their potential in improving outcomes for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging immunotherapies in the treatment of non-small cell lung cancer (NSCLC): the role of immune checkpoint inhibitors. Langer, CJ.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

The relative and absolute benefit of programmed death receptor-1 vs programmed death ligand 1 therapy in advanced non-small-cell lung cancer: A systematic review and meta-analysis. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer: A real-world retrospective cohort study. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

[Immune checkpoint inhibitors in lung cancer]. [2020]

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

Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer. [2022]

6. China pubmed.ncbi.nlm.nih.gov

Adverse events of different PD-1 inhibitors in lung cancer patients: a real-world study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]

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

Safety of Programmed Death-1 Pathway Inhibitors Among Patients With Non-Small-Cell Lung Cancer and Preexisting Autoimmune Disorders. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Acute coronary syndrome and recurrent colitis as immune-related adverse events in a lung cancer patient. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Association of immune-related pneumonitis with the efficacy of PD-1/PD-L1 inhibitors in non-small cell lung cancer. [2022]

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

Current Perspectives in Immunotherapy for Non-Small Cell Lung Cancer. [2020]

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

Emerging immunotherapies in the treatment of non-small cell lung cancer (NSCLC): the role of immune checkpoint inhibitors. [2020]