BG-C9074 + Tislelizumab for Cancer

Recruiting at 40 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BeiGene

Must not be taking: Antibacterials, Antifungals, Antivirals

Disqualifiers: Brain metastasis, Interstitial lung disease, Diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

308 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment using the drug BG-C9074 (an experimental treatment) both alone and with another drug, tislelizumab (an immunotherapy). The main goal is to assess the safety of these treatments and their behavior in the body, while also providing an early evaluation of their effectiveness against advanced solid tumors. The trial includes different groups: some will receive BG-C9074 alone, while others will receive it with tislelizumab. Individuals with advanced cancers that cannot be surgically removed and who have already tried other treatments might be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have an infection requiring treatment with antibiotics, antifungals, or antivirals, you must complete that treatment at least 14 days before starting the trial.

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

Earlier studies found BG-C9074 to be generally safe and manageable for patients with advanced solid tumors. Most side effects were not serious and could be treated by doctors. Common side effects occurred in more than 10% of patients but were usually easy to handle.

When combined with tislelizumab, a type of immunotherapy, BG-C9074 is expected to be similarly safe. Although researchers are still studying the combination, early results suggest it should be safe for patients. Since this is the first time this combination is being tested in humans, researchers are determining the best doses and closely monitoring patient responses. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BG-C9074 and tislelizumab because they offer a fresh approach to cancer treatment. Unlike traditional chemotherapy, BG-C9074 is designed to specifically target cancer cells, potentially reducing harm to healthy cells. Tislelizumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. This combination could enhance the body's natural defenses against cancer, offering hope for more effective and less harmful treatment options.

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

Research has shown that BG-C9074 holds promise for treating advanced solid tumors. It targets B7-H4, a protein often present in various tumors, and has demonstrated early signs of reducing tumor size, particularly in breast and endometrial cancers. The treatment is considered safe and manageable, which is crucial for new therapies. In this trial, some participants will receive BG-C9074 as monotherapy, while others will receive it in combination with tislelizumab, an immunotherapy drug. This combination may enhance the immune system's ability to attack cancer cells. Early results are encouraging, but further research is needed to confirm these findings. ^{1 2 3 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

BeOne Medicines

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors who've had prior treatment. They must have at least one measurable tumor, provide a tissue sample, and use effective birth control. Participants need to be in good health overall and have an ECOG Performance Status of 1 or less, meaning they are fairly active.

Inclusion Criteria

I am able to sign and date a written consent form before any study-specific procedures or data collection.

I have an advanced cancer that cannot be removed by surgery and I've been treated before.

I have at least one tumor that can be measured.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BG-C9074 alone and in combination with tislelizumab until progressive disease, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 3 years

What Are the Treatments Tested in This Trial?

Interventions

• BG-C9074
• Tislelizumab

Trial Overview The study tests BG-C9074 alone and combined with Tislelizumab to assess safety, tolerability, how the body processes the drugs (PK), their effects on the body (PD), and initial effectiveness against tumors. Treatment can last up to two years unless there's disease progression or unacceptable side effects.

How Is the Trial Designed?

Group I: Phase 1b: Monotherapy Dose Expansion Experimental Treatment 1 Intervention

The monotherapy dose expansion phase will begin once the BG-C9074 monotherapy RDFE and dosing schedule have been determined from Parts A and B in Phase 1a.

Group II: Phase 1b: Combination Therapy Dose Expansion (BG-C9074 plus tislelizumab) Experimental Treatment 2 Interventions

This arm will assess BG-C9074 plus tislelizumab as first-line therapy in select solid tumors after completion of the dose escalation phase.

Group III: Phase 1b: Combination Therapy Dose Expansion (BG-C9074 plus bevacizumab) Experimental Treatment 2 Interventions

This arm will assess BG-C9074 plus bevacizumab in select solid tumors participants after establishing the recommended monotherapy dose and schedule.

Group IV: Phase 1a: Part D (Japan Cohort) Experimental Treatment 1 Intervention

A separate cohort in Japan will evaluate the safety of BG-C9074 monotherapy in Japanese participants with select solid tumors

Group V: Phase 1a: Part C (Combination Therapy Dose Escalation) Experimental Treatment 2 Interventions

BG-C9074 plus tislelizumab combination at the recommended dose for expansion (RDFE).

Group VI: Phase 1a: Part B (Monotherapy Safety Expansion) Experimental Treatment 1 Intervention

BG-C9074 dose levels that have been determined to be safe and tolerable in Part A will be investigated.

Group VII: Phase 1a: Part A (Monotherapy Dose Escalation) Experimental Treatment 1 Intervention

BG-C9074 monotherapy dose escalation

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

BeOne Medicines

Lead Sponsor

Published Research Related to This Trial

Tislelizumab, an anti-PD-1 monoclonal antibody, shows improved progression-free survival and objective response rates in treating non-small cell lung cancer (NSCLC), especially when combined with chemotherapy, based on a review of four randomized controlled trials involving 1565 patients.

While tislelizumab is generally effective, it is associated with treatment-emergent adverse events, including significant hematologic issues and immune-mediated effects like hypothyroidism and pneumonitis, with a mortality rate from these events ranging from 3.2% to 4.2%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of tislelizumab, alone or in combination with chemotherapy, for the treatment of non-small cell lung cancer: a systematic review of clinical trials. Daei Sorkhabi, A., ZareDini, M., Fazlollahi, A., et al.[2023]

Tislelizumab is an anti-PD-1 monoclonal antibody developed as an immunotherapy for cancer, specifically approved in December 2019 in China for relapsed or refractory classical Hodgkin's lymphoma after at least two prior chemotherapy treatments.

The drug has shown promise in treating both hematological cancers and advanced solid tumors, indicating its potential for future approvals in additional cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: First Approval. Lee, A., Keam, SJ.[2020]

In a phase II study with 70 patients suffering from relapsed/refractory classical Hodgkin lymphoma, tislelizumab showed a high overall response rate of 87.1% and a complete response rate of 67.1% after a median follow-up of 33.8 months, indicating its efficacy as a treatment option.

The treatment demonstrated a favorable safety profile, with 97.1% of patients experiencing treatment-related adverse events, but only 31.4% having severe (grade ≥3) events, and just 8.6% discontinuing treatment due to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis. Song, Y., Gao, Q., Zhang, H., et al.[2023]

In a phase II study involving Chinese patients with relapsed/refractory classical Hodgkin's lymphoma, tislelizumab demonstrated a high overall response rate of 87.1%, with 62.9% achieving a complete response.

Tislelizumab, a novel anti-PD-1 antibody engineered for improved efficacy, showed promising safety and efficacy, with median progression-free survival and duration of response not yet reached, indicating potential long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab for the treatment of classical Hodgkin's lymphoma. Chen, J., Zhang, H., Zhu, L., et al.[2021]

In a phase I study involving 32 patients with advanced solid tumors, the combination of ociperlimab and tislelizumab was well tolerated, with no dose-limiting toxicities reported and a recommended phase II dose established at ociperlimab 900 mg plus tislelizumab 200 mg every 3 weeks.

Preliminary results showed an overall response rate of 10% and a disease control rate of 50%, indicating some antitumor activity, which supports further investigation in phase II/III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AdvanTIG-105: a phase I dose escalation study of the anti-TIGIT monoclonal antibody ociperlimab in combination with tislelizumab in patients with advanced solid tumors. Frentzas, S., Kao, S., Gao, R., et al.[2023]

Tislelizumab is a modified PD-1 antibody that effectively inhibits tumor growth in various cancers, including Hodgkin's lymphoma and lung cancer, and has received multiple approvals in China for its use.

It has a favorable safety profile with common side effects like fatigue and anemia, and it offers economic advantages over other PD-1 inhibitors, making it a promising option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. Zhang, L., Geng, Z., Hao, B., et al.[2023]

In a phase 3 trial involving 332 patients with advanced nonsquamous non-small cell lung cancer (nsq-NSCLC), the combination of tislelizumab and chemotherapy significantly improved progression-free survival (PFS) compared to chemotherapy alone, with a median PFS of 9.7 months versus 7.6 months.

The addition of tislelizumab also resulted in higher response rates and longer duration of response, making it a promising first-line treatment option for patients with advanced nsq-NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial. Lu, S., Wang, J., Yu, Y., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3033

First-in-human study of BG-C9074, a B7-H4-targeting ADC ... BG-C9074 is an investigational topoisomerase I inhibitor antibody-drug conjugate. This abstract presents the initial results of monotherapy dose escalation.

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06233942

Phase 1a/1b First-in-Human Study of BG-C9074 Alone and ... The RP2D of BG-C9074 will be determined based on safety, PK, pharmacodynamics, preliminary antitumor activity, and other relevant data, as available.

3. beonemedinfo.com beonemedinfo.com/CongressDocuments/Perez_BG-C9074-101_ASCO_Poster_2025.pdf

Table 3. Most Common TEAEs in >10% of Patients Abbreviations: TESAE, treatment-emergent serious adverse event. CONCLUSIONS. • BG-C9074 showed a manageable safety/tolerability profile in ...

4. ascopubs.org ascopubs.org/doi/pdfdirect/10.1200/JCO.2025.43.16_suppl.3033

First-in-human study of BG-C9074, a B7-H4-targeting ADC ... Results: As of January 22, 2025,. 55 patients with advanced tumors (n = 25, ovarian cancer; n = 16, breast cancer; n = 10, cholangiocarcinoma ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06233942

NCT06233942 | Phase 1a/1b First-in-Human Study of BG- ... The RP2D of BG-C9074 will be determined based on safety, PK, pharmacodynamics, preliminary antitumor activity, and other relevant data, as available.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11985252/

B7 Homolog 4 (B7-H4)-Directed Agents in Oncology ... BG-C9074 (DB-1312)[19] + tislelizumab, Ia, Advanced solid tumors ... Trends in safety data reveal that most B7-H4–targeted agents have ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-05419

Phase 1a/1b First-in-Human Study of BG-C9074 Alone and ... This is a first-in-human, dose finding and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary ...