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

Recruiting at 39 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

300 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing mecbotamab vedotin, a medicine that targets and kills cancer cells, in patients with advanced solid tumors, including specific types of sarcomas. It works by using an antibody to find the cancer cells and a drug to destroy them.

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.

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

Research suggests that PD-1 inhibitors, which are part of this treatment, have shown some promise in treating solid tumors, and combining them with other therapies might be more effective for sarcomas. However, sarcomas are complex and challenging to treat, and while PD-1 inhibitors are approved for other cancers, their effectiveness in sarcomas is still being studied. ^{1 2 3 4 5}

Is the combination of CAB-AXL-ADC and PD-1 inhibitors safe for humans?

PD-1 inhibitors, like pembrolizumab, have shown mild side effects in adults, and combining them with other treatments like SBRT in sarcoma patients appeared safe, with no severe toxicities reported. Cabozantinib, a component of CAB-AXL-ADC, has been studied in combination with other drugs and showed manageable safety profiles in various cancers. ^{3 6 7 8 9}

What makes CAB-AXL-ADC + PD-1 Inhibitor unique for treating sarcoma?

CAB-AXL-ADC + PD-1 Inhibitor is unique because it combines a targeted therapy (CAB-AXL-ADC) with an immune checkpoint inhibitor (PD-1 Inhibitor), potentially enhancing the immune system's ability to fight sarcoma by targeting specific cancer pathways and reactivating exhausted T-cells. This approach is different from traditional chemotherapy, which often has limited effectiveness in sarcomas. ^{1 3 10 11 12}

Eligibility Criteria

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

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

Life expectancy of at least three months

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Anti-PD-1 therapy in advanced sarcomas: is cutaneous primary site a stronger predictor of response than histologic subtype? [2023]

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

Prognostic value of programmed death-ligand 1 in sarcoma: a meta-analysis. [2019]

3. England 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. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Recent advances and application of PD-1 blockade in sarcoma. [2020]

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

Status of programmed death-ligand 1 expression in sarcomas. [2019]

6. England 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. [2022]

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

Phase 1 study of cabozantinib in combination with topotecan-cyclophosphamide for patients with relapsed Ewing sarcoma or osteosarcoma. [2023]

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

The Effect of Concurrent Stereotactic Body Radiation and Anti-PD-1 Therapy for Recurrent Metastatic Sarcoma. [2023]

9. Switzerland 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. [2023]

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

PDL1 expression is a poor-prognosis factor in soft-tissue sarcomas. [2021]

11. England 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. [2020]

12. England pubmed.ncbi.nlm.nih.gov

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. [2023]