BA3071 + Nivolumab for Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of BA3071, a new treatment for solid tumors. BA3071 targets a protein called CTLA-4 and is combined with Nivolumab (also known as Opdivo), which helps the immune system attack cancer cells, sometimes alongside chemotherapy. Individuals with certain gene mutations, such as KRAS or STK11, who have not previously received similar treatments, might be suitable candidates. This trial offers a chance to try a potentially powerful new therapy while contributing to cancer research. As a Phase 1/Phase 2 trial, it aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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.

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

Research has shown that BA3071, used alone or with nivolumab, is under careful study for its safety in treating solid tumors. Studies have found that patients tolerated BA3071, either alone or with nivolumab, at doses ranging from 7 mg to 700 mg. Some patients remained progression-free, meaning their cancer did not worsen, for several months.

In trials, some patients with advanced solid tumors received BA3071 and nivolumab, a treatment designed to help the immune system fight cancer. The results were promising, especially since many participants had already tried other treatments without success.

Although these studies are still in the early stages, they provide valuable insight into patient tolerance of this treatment. Researchers have closely monitored side effects, but the treatment appears generally well-tolerated. Ongoing research aims to confirm these findings and further ensure the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BA3071 and its combinations because these treatments offer a unique approach to cancer therapy. Unlike standard treatments that typically target cancer cells directly, BA3071 is a conditionally active biologic (CAB) antibody that targets CTLA-4, a protein playing a crucial role in regulating immune responses. This mechanism enables the immune system to better recognize and attack cancer cells. When combined with a PD-1 inhibitor like Nivolumab, these therapies could enhance immune system activity even further, potentially leading to more effective cancer treatment. Additionally, using these therapies in combination with chemotherapy, both before and after surgery, might improve outcomes by reducing tumor size and preventing recurrence.

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

Research shows that BA3071 may help treat solid tumors. One study found that 9 out of 16 patients had stable disease, meaning their cancer did not worsen. Some patients who received a specific dose experienced extended periods without tumor growth. In this trial, some participants will receive BA3071 alone, while others will receive it in combination with another cancer drug, nivolumab. Studies have shown potential benefits from combining BA3071 with nivolumab, with some patients experiencing confirmed responses, where their tumors shrank or stopped growing. These findings suggest that BA3071, whether alone or combined with nivolumab, might effectively manage certain cancers. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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 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 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]

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]

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]

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 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 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]

Citations

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497 Updated results from a phase 1 study of evalstotug ... This multicenter, open-label, phase 1 study evaluated the safety and antitumor activity of evalstotug ± anti-PD-1 therapy in pts with advanced solid tumors.

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Phase 1 study of BA3071, an anti–CTLA-4 conditionally ... Among 16 efficacy-evaluable patients, 9 experienced stable disease, and 2 out of 5 patients receiving BA3071 in the 350-mg cohort achieved ...

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BioAtla Presenting Phase 1 Evalstotug Clinical Trial Data ... Multiple refractory PD1 failure patients experienced prolonged progression free survival (10 months ongoing); confirmed responses observed ...

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A Phase 1/2 Study of BA3071 in Patients With Solid Tumors The objective of this study is to assess safety and efficacy of BA3071 in solid tumors. Detailed Description. This is a multi-center, open-label study ...

5. researchgate.net researchgate.net/publication/385574767_497_Updated_results_from_a_phase_1_study_of_evalstotug_BA3071_an_anti-CTLA-4_conditionally_active_biologic_with_or_without_nivolumab_in_advanced_solid_tumors

497 Updated results from a phase 1 study of evalstotug ... Among 20 efficacy-evaluable patients, 6 experienced stable disease (disease control rate, 52%), and 3 of 8 patients who received evalstotug 350 ...

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A Phase 1/2 Study of BA3071 in Patients With Solid Tumors This is a multi-center, open-label study designed to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of BA3071.

7. bcan.org bcan.org/clinicaltrials/study-of-ba3071/

Study of BA3071 This is a multi-center, open-label study designed to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of BA3071.