BL-B01D1 for Lung Cancer

Recruiting at 45 trial locations

Overseen By Colandra McDowell

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: SystImmune Inc.

Disqualifiers: Severe heart disease, Autoimmune diseases, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

260 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to evaluate a new treatment called BL-B01D1 (also known as Izalontamab Brengitecan) for individuals with certain types of advanced cancer, such as non-small cell lung cancer (NSCLC) and other solid tumors. Researchers seek to determine the treatment's safety, tolerability, and potential effectiveness. They are testing two different treatment schedules to identify the best approach. Eligible participants typically have advanced cancers that cannot be surgically removed and possess specific genetic markers, which they can confirm with their doctor. The trial is unsuitable for those who have recently undergone other cancer treatments or have certain health conditions. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy, biological therapy, immunotherapy, or other anti-tumor treatments within 4 weeks before starting the trial.

Is there any evidence suggesting that BL-B01D1 is likely to be safe for humans?

Research has shown that BL-B01D1 has promising safety results. In an earlier study, patients generally tolerated BL-B01D1 well at a dose of 2.2 mg/kg, with most side effects being manageable and not serious enough to halt treatment.

These early findings are encouraging, suggesting that BL-B01D1 could be a safe option for individuals with advanced lung cancer and other solid tumors. However, it is important to note that these results come from early trials, and further studies are necessary to confirm them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for lung cancer, which often include chemotherapy or targeted therapies like tyrosine kinase inhibitors, BL-B01D1 is unique because it is administered via intravenous infusion on a precise schedule, either on Day 1 and Day 8 or just Day 1 of each three-week cycle. Researchers are excited about BL-B01D1 because it may offer a novel mechanism of action that targets cancer cells differently than existing therapies, potentially leading to improved outcomes. This approach could provide new hope for patients by enhancing effectiveness and reducing side effects compared to traditional options.

What evidence suggests that BL-B01D1 might be an effective treatment for lung cancer?

Research has shown that Izalontamab Brengitecan (BL-B01D1) may effectively treat certain cancers. In patients with advanced bladder cancer, it shrank tumors in about 44% of cases and controlled the disease in about 88% of patients, stopping cancer growth in many instances. For a type of lung cancer with specific mutations, early studies suggest it could be a valuable treatment. In this trial, participants will receive BL-B01D1 either on Day 1 and Day 8 per cycle or on Day 1 per cycle. While these results are encouraging, they primarily come from studies on different cancer types. More research is needed to confirm its effectiveness specifically for this type of lung cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Jimmy Zhao, MD, PhD

Principal Investigator

SystImmune Inc.

Are You a Good Fit for This Trial?

Adults over 18 with advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) that can't be removed by surgery, who've seen their cancer progress after treatment. They must have a life expectancy of at least 3 months, be in fairly good health otherwise (ECOG PS 0-1), and have a tumor that can be measured. People with autoimmune diseases, mixed lung cancers, recent other treatments or another cancer within the last 5 years, serious infections or heart disease aren't eligible.

Inclusion Criteria

Sign informed consent

You have at least one identifiable abnormality that can be measured according to specific guidelines.

My advanced lung cancer cannot be cured with surgery or radiation, and it has worsened despite treatment.

Exclusion Criteria

I have an active autoimmune or inflammatory disease.

I have severe lung disease or a history of tissue scarring in my lungs.

I haven't had serious blood clot issues needing treatment in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive BL-B01D1 in a dose escalation format to determine the maximum tolerated dose

21-day cycles

Visits on Day 1 and Day 8 per cycle for Cohort A; Day 1 per cycle for Cohort B

Dose Finding

Participants receive BL-B01D1 to find the recommended dose for expansion

21-day cycles

Dose Expansion

Participants receive BL-B01D1 at the recommended dose to further evaluate safety and efficacy

21-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

One year

What Are the Treatments Tested in This Trial?

Interventions

• BL-B01D1

Trial Overview The trial is testing BL-B01D1's safety and effectiveness for NSCLC patients whose cancer has spread and cannot be surgically removed. The study will monitor how well patients tolerate this drug and its impact on their lung cancer.

How Is the Trial Designed?

Group I: BL-B01D1 administered Day 1 per cycle Experimental Treatment 1 Intervention

BL-B01D1 will be administered on Day 1 via by intravenous infusion every 3 weeks

Group II: BL-B01D1 administered Day 1 and Day 8 per cycle Experimental Treatment 1 Intervention

BL-B01D1 will be administered on Day 1 and Day 8 by intravenous infusion every 3 weeks

Who Is Running the Clinical Trial?

SystImmune Inc.

Lead Sponsor

Trials

23

Recruited

1,800+

Published Research Related to This Trial

Sugemalimab, a new PD-L1 inhibitor, is being explored as a treatment option for advanced non-small cell lung cancer (NSCLC), which often presents as locally advanced or metastatic disease at diagnosis.

Current treatment for metastatic NSCLC primarily involves immunotherapy, sometimes combined with chemotherapy, highlighting the importance of novel therapies like sugemalimab in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sugemalimab, a novel PD-L1 inhibitor for treatment of advanced or metastatic non-small cell lung cancer. Sakamoto, M., Jimeno, A.[2023]

In a study of 170 patients with advanced non-squamous non-small-cell lung cancer, axitinib combined with pemetrexed and cisplatin showed a higher objective response rate (45.5% and 39.7%) compared to chemotherapy alone (26.3%).

While the combination therapy did not significantly improve progression-free survival compared to chemotherapy alone, it was generally well tolerated, with hypertension being the most common serious side effect in the axitinib groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer. Belani, CP., Yamamoto, N., Bondarenko, IM., et al.[2021]

In a clinical trial involving 42 patients with advanced non-small-cell lung cancer, the combination of topotecan and bevacizumab resulted in a median progression-free survival of 5.1 months and an overall survival of 11.5 months, indicating potential efficacy as a second-line treatment.

The treatment was generally well tolerated, although some patients experienced significant hematologic toxicities, including grade 3 thrombocytopenia and neutropenia, and there was one toxic death due to pulmonary hemorrhage, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of topotecan and bevacizumab in advanced, refractory non--small-cell lung cancer. Powell, SF., Beitinjaneh, A., Tessema, M., et al.[2021]

Amivantamab-vmjw has shown a 40% overall response rate in patients with metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, based on a phase 1 trial involving 81 participants, indicating its efficacy after platinum-based chemotherapy.

The treatment resulted in a median progression-free survival of 8.3 months and an overall survival of 22.8 months, with an acceptable safety profile, marking it as a significant advancement for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab-Vmjw: A Novel Treatment for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutation after Progression on Platinum-Based Chemotherapy. Shah, V., McNatty, A., Simpson, L., et al.[2023]

In a phase 2 trial involving 38 patients with high tumor mutation burden (TMB) advanced nonsquamous non-small cell lung cancer (NSCLC), the combination of atezolizumab and bevacizumab achieved a 12-month progression-free survival (PFS) rate of 51.3%, indicating significant clinical benefit for this patient group.

The treatment also demonstrated a 12-month overall survival (OS) rate of 72.0%, with most adverse events being mild (grade 1 or 2), suggesting that this combination therapy is both effective and relatively safe for patients with high-TMB NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab Plus Bevacizumab as First-line Treatment for Patients With Metastatic Nonsquamous Non-Small Cell Lung Cancer With High Tumor Mutation Burden: A Nonrandomized Controlled Trial. Provencio, M., Ortega, AL., Coves-Sarto, J., et al.[2023]

In a study of 113 non-small-cell lung cancer (NSCLC) patients with brain metastases, combining PD-1 inhibitors with anti-angiogenic therapy significantly improved overall survival (OS) to 21.4 months compared to 11.8 months for those on PD-1 monotherapy.

The combination therapy also showed a better intracranial disease control rate (iDCR), indicating enhanced effectiveness in managing brain metastases, without increasing the risk of severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of PD-1 Inhibitors Combined with Anti-Angiogenic Therapy in Driver Gene Mutation Negative Non-Small-Cell Lung Cancer with Brain Metastases. Song, JQ., Wang, X., Zeng, ZM., et al.[2023]

In a study of 118 stage IV non-small cell lung cancer patients, combining docetaxel with a PD-1/PD-L1 inhibitor significantly improved the disease control rate (89.9% vs. 73.5%) compared to the PD-1/PD-L1 inhibitor alone.

While the combination treatment did not show a significant difference in overall response rates or 1-year progression-free survival, it was associated with a higher incidence of bone marrow suppression, although most adverse reactions were mild and tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Analysis of Docetaxel Combined with PD-1/PD-L1 Inhibitor in Second-line Treatment of Advanced Non-small Cell Lung Cancer]. Chen, Q., Li, Y., Zhang, W., et al.[2022]

This phase I/II clinical trial is investigating the safety and efficacy of a combination treatment involving selumetinib, tremelimumab, and durvalumab in 40 patients with previously treated, unresectable non-small-cell lung cancer (NSCLC).

The study aims to determine the maximum tolerated dose and progression-free survival, while also exploring biomarkers of response and resistance, which could help tailor future treatments for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC: Early Trial Report. Gaudreau, PO., Lee, JJ., Heymach, JV., et al.[2021]

ZD6474 effectively targets two important pathways in tumor growth, inhibiting both tumor angiogenesis and cell proliferation, which suggests a dual mechanism of action in fighting cancer.

Phase I trials indicate that ZD6474 is generally well tolerated and suitable for once-daily oral dosing, with ongoing Phase II studies comparing its efficacy against standard treatments in non-small-cell lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZD6474--clinical experience to date. Heymach, JV.[2023]

In a study of 1,090 patients with advanced nonsquamous non-small-cell lung cancer (NSCLC), the combination of motesanib with carboplatin/paclitaxel did not significantly improve overall survival compared to chemotherapy alone, with median survival times of 13.0 months versus 11.0 months, respectively.

While motesanib showed a higher objective response rate (40% vs. 26%) and slightly longer progression-free survival (5.6 months vs. 5.4 months), it also resulted in a higher incidence of severe adverse events (73% vs. 59%), indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

International, randomized, placebo-controlled, double-blind phase III study of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous non-small-cell lung cancer: MONET1. Scagliotti, GV., Vynnychenko, I., Park, K., et al.[2018]

Citations

1. onclive.com onclive.com/view/izalontamab-brengitecan-data-reinforce-the-value-of-adcs-in-advanced-urothelial-carcinoma

Izalontamab Brengitecan Data Reinforce the Value of ... Izalontamab brengitecan showed a 44.1% objective response rate and 88.2% disease control rate in advanced urothelial carcinoma patients. The ...

2. news.bms.com news.bms.com/news/corporate-financial/2025/Izalontamab-Brengitecan-EGFRxHER3-ADC-Granted-Breakthrough-Therapy-Designation-by-U-S--FDA-for-Patients-with-Previously-Treated-Advanced-EGFR-Mutated-Non-Small-Cell-Lung-Cancer/default.aspx

Izalontamab Brengitecan (EGFRxHER3 ADC) Granted ... “The data we have generated to date suggest that iza-bren could address a critical unmet need in patient care, and we look forward to working ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07100080

Study of Izalontamab Brengitecan (BMS-986507) Versus ... IZABRIGHT-Lung01: A Randomized, Open-label, Phase 2/3 Study of Izalontamab Brengitecan (BMS-986507) Versus Platinum-based Chemotherapy in Patients With ...

4. ascopost.com ascopost.com/news/september-2025/novel-adc-under-study-in-previously-treated-egfr-mutated-nsclc/

Novel ADC Under Study in Previously Treated EGFR- ... One case of grade 1 interstitial lung disease was reported. Going forward, izalontamab brengitecan is being evaluated further in an ongoing ...

5. oncologypipeline.com oncologypipeline.com/apexonco/esmo-2025-iza-brens-us-backing-comes-toxicity

ESMO 2025 – iza-bren's US backing comes with toxicity The trial, described as iza-bren's first global study to yield data, mostly concerned lung cancer, plus several other heavily pretreated tumours ...

6. systimmune.com systimmune.com/news---systimmune-inc-to-present-new-clinical-data-on-izalontamab-brengitecan-and-bl-m07d1-highlighting-strength-of-differentiated-antibody-drug-conjugate-adc-platform

News - SystImmune, Inc. to Present New Clinical Data ... SystImmune, Inc. to Present New Clinical Data on Izalontamab Brengitecan and BL-M07D1 Highlighting Strength of Differentiated Antibody Drug ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06838273

NCT06838273 | A Study of BL-B01D1 in Combination With ... This trial is a registered phase III, randomized, open-label, multicenter study to evaluate the efficacy and safety of BL-B01D1 in combination with ...

8. oncozine.com oncozine.com/esmo-2025-first-phase-1-safety-and-efficacy-data-presented-of-izalontamab-brengitecan-in-patients-with-advanced-solid-tumors/

ESMO 2025: First Phase 1 Safety and Efficacy Data ... The US-Lung-101 study (NCT05983432), a global, multi-center, phas 1 study, evaluated the safety and efficacy of Izalontamab Brengitecan in ...