CAB-AXL-ADC + PD-1 Inhibitor for Sarcoma

No longer recruiting at 43 trial locations

Overseen By BioAtla Medical Affairs

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 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)

Compensation: Varies

Number of Visits: Unknown

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 to determine its safety and effectiveness for people with solid tumors, specifically sarcoma. In Phase 1, all participants will receive the treatment. In Phase 2, some will receive the treatment alone, while others will receive it combined with a PD-1 inhibitor, a drug that helps the immune system fight cancer. This trial suits those diagnosed with sarcoma who have measurable disease and are not experiencing severe heart problems or uncontrolled cancer spread to the brain. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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

The trial information 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 shows that the treatment mecbotamab vedotin (also known as CAB-AXL-ADC) appears promising in early studies. It targets a specific protein found in many cancers. In these studies, patients with sarcoma received the treatment, providing information about its safety.

In the early stages, patients tolerated the treatment well. Some side effects occurred, but they were generally manageable. While some patients experienced unwanted effects, they were not severe enough to halt the treatment.

When combined with a PD-1 inhibitor (a drug that helps the immune system fight cancer), the treatment maintained a similar safety profile. This suggests that adding the PD-1 inhibitor did not significantly increase the risk of serious side effects.

Overall, while the treatment remains under study, early findings indicate that it is well-tolerated in patients with sarcoma. Although there are risks, the treatment has shown relative safety so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CAB-AXL-ADC and its combination with a PD-1 inhibitor for treating sarcoma because these treatments offer a novel approach compared to traditional chemotherapy or targeted therapies. CAB-AXL-ADC is an antibody-drug conjugate designed to specifically target and deliver chemotherapy to cancer cells expressing the AXL protein, potentially reducing damage to healthy cells. The combination with a PD-1 inhibitor aims to also enhance the immune system's ability to fight cancer, providing a dual mechanism of action that could improve outcomes for patients with sarcoma. This targeted and immune-based strategy represents a promising advancement over existing treatment options.

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

Studies have shown that CAB-AXL-ADC, also known as mecbotamab vedotin, shows promise in treating certain types of sarcomas, which develop in bones and soft tissues. Research indicates that for patients with difficult-to-treat sarcomas like leiomyosarcoma and liposarcoma, this treatment led to a median overall survival of 21.5 months, meaning half of the patients lived longer than 21.5 months after starting the treatment. The drug targets AXL, a protein often found in high amounts in many cancers, known to help tumors grow. 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 helps the immune system attack cancer cells, and the combination aims to overcome the resistance some tumors have to standard therapies. Early findings suggest that this combination could enhance the body's ability to fight cancer cells more effectively. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adolescents and adults with various types of sarcoma, including Ewing Sarcoma and Osteosarcoma. Participants need to have a life expectancy of at least three months, be aged 12 or older (for Phase 2), and have good kidney, liver, and blood function. They should also be relatively active (ECOG status of 0 or 1). People who've had certain prior therapies, significant heart disease, uncontrolled brain metastasis, severe allergies to monoclonal antibodies or components used in the study are excluded.

Inclusion Criteria

Life expectancy of at least three months

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

I am 12 years old or older.

Exclusion Criteria

I do not have uncontrolled brain metastases.

I have never had a severe allergic reaction to monoclonal antibody therapy.

I have not had major surgery in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase 1 dose escalation to determine the safety and tolerability of BA3011

Enrollment complete as of Oct 2019

Dose Expansion

Phase 1 dose expansion to further evaluate safety and efficacy

Enrollment complete as of Jan 2024

Phase 2 Part 1

Evaluation of mecbotamab vedotin alone and with nivolumab in advanced sarcomas

Enrollment complete as of Jan 2024

Phase 2 Part 2

Evaluation of safety and efficacy in patients with UPS and MFS

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• CAB-AXL-ADC
• PD-1 inhibitor

Trial Overview The trial is testing CAB-AXL-ADC's safety and effectiveness against solid tumors in patients with sarcoma. It will also involve a PD-1 inhibitor as part of the treatment regimen. The goal is to see how well these interventions work together in treating different kinds of sarcomas.

How Is the Trial Designed?

Group I: Combination Therapy Experimental Treatment 2 Interventions

Phase 2: BA3011 in combination with PD-1 inhibitor.

Group II: BA3011 Experimental Treatment 1 Intervention

Phase 1: All patients will receive BA3011, CAB-AXL-ADC. Phase 2: All patients will receive either BA3011 alone or in combination with PD-1 inhibitor.

Who Is Running the Clinical Trial?

BioAtla, Inc.

Lead Sponsor

Trials

7

Recruited

1,500+

Published Research Related to This Trial

In a phase 2 study involving 86 patients with advanced soft-tissue or bone sarcoma, pembrolizumab demonstrated some efficacy, particularly in undifferentiated pleomorphic sarcoma (40% response rate) and dedifferentiated liposarcoma (20% response rate), although the overall response rate did not meet the primary endpoint.

The treatment was associated with some serious adverse events, including immune-related conditions like adrenal insufficiency and pneumonitis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Tawbi, HA., Burgess, M., Bolejack, V., et al.[2022]

Cabozantinib, which inhibits multiple receptor tyrosine kinases, is being evaluated in combination with the PD-L1 inhibitor atezolizumab for its potential to enhance treatment responses in men with metastatic castration-resistant prostate cancer (mCRPC).

A phase III trial (NCT04446117) is being designed to compare the efficacy of cabozantinib plus atezolizumab against a second novel hormone therapy in patients with mCRPC who have previously received hormone treatments, addressing a significant need for effective options in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III, randomized, open-label study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy in patients with metastatic castration-resistant prostate cancer. Agarwal, N., Azad, A., Carles, J., et al.[2022]

In a phase 2 trial involving 33 patients with advanced sarcomas, the combination of axitinib and pembrolizumab showed a promising 3-month progression-free survival rate of 65.6%, with even higher rates of 72.7% for patients with alveolar soft-part sarcoma (ASPS).

The treatment was associated with manageable side effects, with 21% of patients experiencing serious adverse events, but no treatment-related deaths, indicating a favorable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial. Wilky, BA., Trucco, MM., Subhawong, TK., et al.[2020]

In a phase 2 trial involving 62 patients with advanced or metastatic sarcoma, the combination of durvalumab and tremelimumab showed a promising progression-free survival rate of 49% at 12 weeks, indicating its potential efficacy as a treatment option.

While the treatment was generally active, it was associated with some serious adverse events, including one case of grade 5 pneumonitis and colitis, highlighting the need for careful monitoring of patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. Somaiah, N., Conley, AP., Parra, ER., et al.[2023]

In a study of five patients with metastatic sarcoma treated with SBRT and concurrent pembrolizumab, the combination was found to be safe, with no severe (grade 5) toxicities reported and only manageable side effects observed.

The treatment resulted in high local control rates, with two patients showing enhanced tumor regression or potential abscopal effects, suggesting that this combination may improve outcomes in metastatic sarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Concurrent Stereotactic Body Radiation and Anti-PD-1 Therapy for Recurrent Metastatic Sarcoma. Callaghan, CM., Seyedin, SN., Mohiuddin, IH., et al.[2023]

In a study involving 93 pediatric patients, PD-1 inhibitor-based regimens showed promising efficacy with an overall response rate (ORR) of approximately 54% to 100% across different treatment combinations, indicating potential effectiveness in treating pediatric malignancies.

The safety profile was generally acceptable, with adverse events (AEs) occurring in 83% to 100% of patients depending on the treatment regimen, suggesting that while side effects are common, they may be manageable in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of programmed cell death receptor 1 inhibition-based regimens in patients with pediatric malignancies: the real-world study in China. Hong, Y., Song, M., Lan, Y., et al.[2023]

In a study of 84 patients with advanced sarcomas treated with off-label anti-PD1 immunotherapy, those with cutaneous primary tumors showed a significantly higher clinical benefit rate of 58%, compared to 11% for non-cutaneous tumors, indicating that tumor location is a key factor in treatment efficacy.

Patients with cutaneous sarcomas also experienced longer progression-free survival (8.6 months vs. 2.5 months) and overall survival (19.0 months vs. 9.2 months), suggesting that cutaneous primary site is a stronger predictor of response to immunotherapy than histological subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1 therapy in advanced sarcomas: is cutaneous primary site a stronger predictor of response than histologic subtype? Miao, R., Swank, J., Melzer, D., et al.[2023]

In a Phase 1 study involving 12 patients with relapsed osteosarcoma and Ewing sarcoma, the combination of cabozantinib, topotecan, and cyclophosphamide showed acceptable toxicity levels, with manageable dose-limiting toxicities observed.

The treatment resulted in one partial response and stable disease in seven patients, suggesting that this combination therapy may provide potential disease control in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of cabozantinib in combination with topotecan-cyclophosphamide for patients with relapsed Ewing sarcoma or osteosarcoma. Campbell, K., Posner, A., Chen, N., et al.[2023]

Citations

1. 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.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03425279

NCT03425279 | CAB-AXL-ADC Safety and Efficacy Study ... This is a multi-center, open-label, Phase 1/2 study designed to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of mecbotamab ...

3. ir.bioatla.com ir.bioatla.com/news-releases/news-release-details/bioatla-present-clinical-data-mecbotamab-vedotin-ba3011-soft

BioAtla to Present Clinical Data for Mecbotamab Vedotin ... The presentation, titled “Median OS of 21.5 months among 44 patients with treatment-refractory leiomyosarcoma, liposarcoma, and undifferentiated ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT03425279

CAB-AXL-ADC Safety and Efficacy Study in Adult and ... Full interim data set of approximately 20 patients anticipated this year; (ii) AXL-positive Soft Tissue and Primary Bone Sarcomas: Continuing to enroll across ...

5. 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.

6. bioatla.com bioatla.com/wp-content/uploads/2023/04/CTOS-2021-BA3011-001-Ph-1-Poster.pdf

Interim Safety and Efficacy Results from Phase 1/2 Study of ... In Phase 1 sarcoma patients, evidence of antitumor activity was observed, with higher. AXL tumor membrane expression correlating with response.

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.