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

Recruiting at 67 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

85 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CAB-AXL-ADC, an experimental drug, both alone and with a PD-1 inhibitor, a type of immunotherapy, to assess its safety and effectiveness for people with non-small cell lung cancer (NSCLC). Researchers aim to determine if these treatments can control the cancer better than current options. Individuals with measurable lung cancer and a life expectancy of at least three months might be suitable for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer therapy.

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.

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

Research has shown that CAB-AXL-ADC, also known as BA3011, is under evaluation for safety in treating advanced solid tumors, including lung cancer. In a study involving 40 lung cancer patients, some received only CAB-AXL-ADC, while others received it with a PD-1 inhibitor. The results indicated that the treatment was generally well-tolerated, though some patients experienced side effects.

For those taking both CAB-AXL-ADC and a PD-1 inhibitor, common side effects of PD-1 inhibitors include immune-related issues such as inflammation of the lungs or colon. Awareness of these possibilities is important, but many patients handle the treatments well.

This trial is in Phase 2, indicating that the treatment has passed initial safety tests. It is now being evaluated for effectiveness and any additional side effects. This stage is encouraging, but monitoring patient responses remains crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CAB-AXL-ADC (BA3011), both alone and in combination with a PD-1 inhibitor, for lung cancer because these treatments offer a new approach compared to existing therapies like chemotherapy and targeted therapies such as EGFR inhibitors. CAB-AXL-ADC is an antibody-drug conjugate that specifically targets the AXL receptor, which is often overexpressed in cancer cells. This targeted approach allows the drug to deliver cytotoxic agents directly to the cancer cells, potentially reducing damage to healthy cells and improving efficacy. When combined with a PD-1 inhibitor, it may also enhance the immune system's ability to recognize and attack cancer cells, offering a powerful one-two punch against the disease.

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

Research has shown that CAB-AXL-ADC holds promise for treating non-small cell lung cancer (NSCLC). In a study with patients who had already tried several treatments, this therapy demonstrated benefits, effectively targeting cancer cells. In this trial, some participants will receive CAB-AXL-ADC alone, while others will receive it with a PD-1 inhibitor. The PD-1 inhibitor, often paired with CAB-AXL-ADC, has successfully treated advanced NSCLC by enhancing the immune system's ability to attack cancer cells. Combining these treatments could enhance their effectiveness, as studies in mice have shown significant tumor reduction with similar therapies. Overall, early results suggest that this combination might be a strong option for treating NSCLC. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. ir.bioatla.com ir.bioatla.com/news-releases/news-release-details/bioatla-presented-phase-2-clinical-trial-data-iaslc-2023-north

BioAtla Presented Phase 2 Clinical Trial Data at the IASLC ... Results from the Phase 2 BA3011 clinical non-small cell lung cancer (NSCLC) study demonstrated promising clinical benefits in heavily pre-treated non-squamous ...

2. esmoopen.com esmoopen.com/article/S2059-7029(24)00211-4/fulltext

53O Results from a phase II part I trial of mecbotamab ... 53O results from a phase II part I trial of mecbotamab vedotin (BA3011), a CAB-AXL-ADC, in patients with advanced refractory sarcoma.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04681131

NCT04681131 | CAB-AXL-ADC Safety and Efficacy Study ... This is a multi-center, open-label, Phase 2 study designed to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of BA3011, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12146481/

Preclinical development of mecbotamab vedotin (BA3011), a ... AXL, a tyrosine kinase receptor, is over-expressed in many solid and hematologic cancers, promoting progression and poor clinical outcomes.

5. jto.org jto.org/article/S1556-0864(24)00360-5/fulltext

PPD01.07 Phase 2 Trial of Mecbotamab Vedotin (BA3011), ... Results. Forty patients with stage IV non-squamous NSCLC were treated; 23 patients received BA3011 monotherapy, and 17 patients received BA3011 + nivolumab.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04681131?term=AREA%5BInterventionSearch%5D(BA3011)%20AND%20AREA%5BOverallStatus%5D(RECRUITING%20OR%20NOT_YET_RECRUITING%20OR%20ACTIVE_NOT_RECRUITING%20OR%20ENROLLING_BY_INVITATION)&rank=1

CAB-AXL-ADC Safety and Efficacy Study in Adults With ... This is a multi-center, open-label, Phase 2 study designed to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of BA3011, ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e15010

Population pharmacokinetic and exposure-response safety ... BA3011 is being developed for the treatment patients with advanced solid tumors including sarcoma with AXL expression.