BA3071 + Nivolumab for Cancer

Recruiting at 13 trial locations

Overseen By BioAtla Medical Affairs

Age: 18+

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

Duration: 24 months

320 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of this study is to assess safety and efficacy of BA3071 in solid tumors

Will I have to stop taking my current medications?

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 combination BA3071 + Nivolumab for cancer?

Research shows that Nivolumab, a part of this drug combination, has been effective in improving survival in patients with advanced melanoma and has shown activity in treating advanced lung cancer. This suggests potential benefits when used in combination with other treatments like BA3071. ^{1 2 3 4 5}

What safety information is available for Nivolumab in cancer treatment?

Nivolumab, used in cancer treatment, can cause immune-related side effects, including issues with the thyroid and other endocrine (hormone-related) problems. These side effects may limit the safety and continuation of therapy. ^{5 6 7 8 9}

What makes the drug BA3071 + Nivolumab unique for cancer treatment?

BA3071 + Nivolumab is unique because it combines a novel treatment, BA3071 (Evalstotug), with Nivolumab, an established immune checkpoint inhibitor that blocks PD-1 to enhance the body's immune response against cancer. This combination may offer a new approach by potentially improving the effectiveness of Nivolumab, which has already shown benefits in various cancers. ^{1 5 7 10 11}

Eligibility Criteria

This trial is for adults (18+) with various advanced solid tumors who haven't been treated with CLTA-4 blocking antibodies. They must be in good physical condition, have normal blood, liver, and kidney functions, and measurable disease. Pregnant or breastfeeding women, those with recent major surgery, significant heart issues, uncontrolled brain metastases or severe allergies to monoclonal antibodies can't participate.

Inclusion Criteria

I am fully active or can carry out light work.

I have never received CTLA-4 blocking-antibody treatment.

My blood counts are within normal ranges.

Exclusion Criteria

I do not have uncontrolled brain metastases.

I do not have any serious heart conditions.

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

Treatment

Participants receive BA3071 in combination with PD-1 inhibitor and chemotherapy to evaluate safety, tolerability, PK, immunogenicity, and antitumor activity

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• BA3071
• Nivolumab

Trial Overview The study tests the safety and effectiveness of BA3071 alone and combined with PD-1 blockers Pembrolizumab or Nivolumab in treating solid tumors. It aims to find out how well these treatments work against different types of cancer.

Participant Groups

Group I: Neoadjuvant Combination Therapy + Chemotherapy Experimental Treatment 3 Interventions

Conditionally active biologic (CAB) antibody that binds to CTLA-4 with PD-1 inhibitor + Chemotherapy prior to surgical resection

Group II: Combination Therapy + Chemotherapy Experimental Treatment 3 Interventions

Conditionally active biologic (CAB) antibody that binds to CTLA-4 with PD-1 inhibitor + Chemotherapy

Group III: Combination Therapy Experimental Treatment 3 Interventions

Conditionally active biologic (CAB) antibody that binds to CTLA-4 with PD-1 inhibitor

Group IV: BA3071 Experimental Treatment 1 Intervention

Conditionally active biologic (CAB) antibody that binds to CTLA-4

Who Is Running the Clinical Trial?

BioAtla, Inc.

Lead Sponsor

Trials

7

Recruited

1,500+

Findings from Research

In a phase 2 trial involving 117 patients with advanced, refractory squamous non-small-cell lung cancer, nivolumab demonstrated a 14.5% objective response rate, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with 17% of patients experiencing severe treatment-related adverse events, suggesting that while there are risks, the benefits may outweigh them for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Rizvi, NA., Mazières, J., Planchard, D., et al.[2022]

In a study of 43 patients with non-small cell lung cancer, nivolumab showed the highest median progression-free survival (12.6 months) and overall survival (13.4 months), particularly in patients with fewer metastases and better performance status.

While 85% of patients experienced some adverse effects, the development of vitiligo in patients treated with nivolumab was associated with a more durable response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in metastatic non-small cell lung cancer. Burgos-San José, A., Colomer-Aguilar, C., Martínez-Caballero, D., et al.[2021]

In a subgroup analysis of the CheckMate 025 study involving 406 patients with advanced renal cell carcinoma, 48% of those who progressed by RECIST criteria continued treatment with nivolumab and showed a 13% rate of tumor burden reduction post-progression.

Patients who continued nivolumab treatment beyond RECIST progression had a lower incidence of treatment-related adverse events after progression (59%) compared to before (71%), indicating a favorable safety profile for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025. Escudier, B., Motzer, RJ., Sharma, P., et al.[2022]

In a study of 37 patients with stage IV metastatic melanoma, high levels of soluble CD73 (sCD73) enzyme activity in the serum were linked to significantly poorer overall survival and progression-free survival when treated with nivolumab.

Patients with high sCD73 activity had a median progression-free survival of only 2.6 months compared to 14.2 months for those with lower activity, suggesting that measuring sCD73 could help predict how well patients will respond to nivolumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab. Morello, S., Capone, M., Sorrentino, C., et al.[2018]

Nivolumab is shown to be the most cost-effective treatment option for advanced melanoma patients in England, with incremental cost-effectiveness ratios of £24,483 for BRAF mutation-negative and £17,362 for mutation-positive patients.

The analysis utilized a Markov state-transition model based on patient-level data from clinical trials, indicating that nivolumab provides long-term survival benefits while being economically favorable compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Meng, Y., Hertel, N., Ellis, J., et al.[2020]

In a study of 35 patients with advanced non-small-cell lung cancer treated with nivolumab, 34.3% experienced immune-related endocrine adverse events (irAEs), primarily thyroid dysfunction, with hyperthyroidism occurring in 22.9% and hypothyroidism in 8.6%.

Despite the occurrence of these endocrine irAEs, which were mostly mild to moderate in severity, patients with these side effects had a longer progression-free survival, although the study did not find a direct link between irAEs and improved cancer prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do endocrine adverse events predict longer progression-free survival among patients with non-small-cell lung cancer receiving nivolumab? Chmielewska, I., Dudzińska, M., Szczyrek, M., et al.[2021]

In a study of 40 patients with advanced non-small cell lung cancer treated with nivolumab, 22.5% experienced thyroid function changes, including hypothyroidism and hyperthyroidism, highlighting the need for regular monitoring of thyroid health during treatment.

Despite the occurrence of thyroid-related immune adverse events, 62.5% of patients showed a positive response to nivolumab after a median follow-up of 7.6 months, indicating that while endocrine IRAEs are common, they do not necessarily correlate with treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-induced thyroid dysfunction in patients with lung cancer. Ramos-Levi, AM., Rogado, J., Sanchez-Torres, JM., et al.[2021]

Nivolumab, an immune checkpoint inhibitor, shows strong antitumor activity but is associated with immune-related adverse events that can affect patient safety and treatment continuation, necessitating careful monitoring.

Long-term safety data, including a 5-year follow-up, suggests that nivolumab can be safely administered to various challenging patient subgroups, but identifying biomarkers for severe toxicity could improve patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. Czarnecka, AM., Rutkowski, P.[2021]

In a study of 1255 patients with metastatic non-small cell lung cancer (NSCLC), first-line treatment with nivolumab plus ipilimumab (NIVO+IPI) showed a high incidence of treatment-related adverse events (TRAEs), with 78% experiencing any-grade TRAEs and 34% experiencing severe (grade 3 or 4) TRAEs, but the treatment was generally well tolerated.

Patients who discontinued NIVO+IPI due to TRAEs still had a favorable long-term survival rate, with a 3-year overall survival of 50%, indicating that stopping treatment because of side effects did not negatively impact their long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. Paz-Ares, LG., Ciuleanu, TE., Pluzanski, A., et al.[2023]

In a study of 88 patients with metastatic melanoma, higher serum concentrations of nivolumab were significantly correlated with better clinical outcomes, including overall and progression-free survival.

Patients who achieved a clinical response not only had higher nivolumab levels but also exhibited a distinct genetic profile with increased activation of genes related to T-cell activation, suggesting that both drug concentration and genetic factors may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab serum concentration in metastatic melanoma patients could be related to outcome and enhanced immune activity: a gene profiling retrospective analysis. Mallardo, D., Giannarelli, D., Vitale, MG., et al.[2023]

In a study of 79 pre-treated patients with advanced non-small cell lung cancer, nivolumab significantly prolonged progression-free survival, especially in patients who had a partial response to prior treatments.

The occurrence of skin rash during nivolumab treatment was associated with improved long-term survival, suggesting that this side effect may indicate a favorable response to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Pleiotropic Effects of Nivolumab in Pretreated Advanced or Recurrent Non-small Cell Lung Cancer Cases. Akano, Y., Kuribayashi, K., Funaguchi, N., et al.[2020]

References

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

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in metastatic non-small cell lung cancer. [2021]

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

Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. [2020]

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

Do endocrine adverse events predict longer progression-free survival among patients with non-small-cell lung cancer receiving nivolumab? [2021]

7. Spain pubmed.ncbi.nlm.nih.gov

Nivolumab-induced thyroid dysfunction in patients with lung cancer. [2021]

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

An update on the safety of nivolumab for the treatment of advanced melanoma. [2021]

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

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. [2023]

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

Nivolumab serum concentration in metastatic melanoma patients could be related to outcome and enhanced immune activity: a gene profiling retrospective analysis. [2023]

11. Greece pubmed.ncbi.nlm.nih.gov

Analysis of Pleiotropic Effects of Nivolumab in Pretreated Advanced or Recurrent Non-small Cell Lung Cancer Cases. [2020]