BCA101 + Pembrolizumab for Cancer

Recruiting at 20 trial locations

Overseen By David Bohr

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bicara Therapeutics

Must not be taking: Anti-EGFR, Anti-TGFβ, Corticosteroids

Disqualifiers: Pregnancy, Breastfeeding, HIV, others

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

Compensation: Varies

Number of Visits: 101

292 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new drug, BCA101 (also known as Ficerafusp Alfa), which may treat certain cancers by targeting specific proteins involved in tumor growth. The trial consists of two parts: one tests BCA101 alone, and the other combines it with pembrolizumab, another cancer treatment. It seeks participants with specific types of cancer, such as skin, head and neck, anal, lung, and colorectal cancers, who have not succeeded with other treatments. Participants should have measurable tumors and be willing to provide biopsy samples for research. 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 drug.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on certain treatments like corticosteroids above a specific dose or certain antiviral therapies. It's best to discuss your current medications with the trial team.

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

Research has shown that BCA101, tested alone and with pembrolizumab, has a manageable safety profile. "Manageable" means that any side effects can be controlled or treated.

When tested alone, studies found BCA101 was generally well-tolerated, indicating that most people did not experience serious problems from the treatment. Some mild to moderate side effects occurred, but they were not severe.

For BCA101 combined with pembrolizumab, the safety results were similar, with a manageable safety profile. This means that while side effects might occur, they are generally not too serious and can be managed with care.

Overall, the safety data for both BCA101 alone and with pembrolizumab indicate that the treatment is tolerable for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BCA101 because it offers a novel approach to cancer treatment by targeting the epidermal growth factor receptor (EGFR) and transforming growth factor-beta (TGF-β) pathways simultaneously. Unlike standard treatments that typically focus on a single pathway, BCA101's dual-action approach may enhance anti-tumor effects and potentially reduce resistance. Additionally, the combination of BCA101 with pembrolizumab, an established immunotherapy, might enhance the immune system's ability to attack cancer cells more effectively, offering hope for improved outcomes compared to current therapies.

What evidence suggests that BCA101 might be an effective treatment for cancer?

Research has shown that BCA101, which participants in this trial may receive as monotherapy, has potential in treating certain cancers. In one study, 38% of patients experienced stable disease, meaning their cancer did not worsen. However, only one out of 42 patients showed a significant reduction in tumor size.

Another treatment arm in this trial involves combining BCA101 with pembrolizumab. Studies indicate that this combination yields more encouraging results, with 31% of patients responding positively and some experiencing noticeable tumor shrinkage. These findings suggest that the combination might be more effective, especially for difficult-to-treat cancers. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients with advanced solid tumors driven by EGFR, such as certain types of anal, head and neck, lung cancers, and more. Participants must have tried some treatments already without success or been unable to tolerate them. They should be relatively healthy otherwise (performance status ≤1) and willing to undergo tumor biopsies.

Inclusion Criteria

My cancer is advanced anal canal squamous carcinoma, and I've had 1-2 treatments.

I can carry out all my self-care but cannot do heavy physical work.

My scans show at least one tumor that can be measured.

Exclusion Criteria

I have chronic HBV with active disease and am not on antiviral therapy.

I have not been treated with anti-TGFβ therapy before.

I've had a bad reaction to cetuximab or similar drugs before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of BCA101 monotherapy or BCA101 in combination with pembrolizumab to determine the maximum tolerated dose

21 days

Weekly visits for BCA101 monotherapy, every 3 weeks for combination therapy

Expansion Cohorts

Participants receive treatment at the recommended dose in select tumor types to further evaluate safety and efficacy

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• BCA101

Trial Overview BCA101 is being tested alone or with Pembrolizumab in this study. BCA101 targets both EGFR and TGFβ which might work well together against tumors that are driven by EGFR. The trial will see how safe it is and how well people can handle it.

How Is the Trial Designed?

Group I: BCA101 Monotherapy Experimental Treatment 1 Intervention

Route: IV Infusion Frequency: QW Current Dose: 1500mg

Group II: BCA101 + pembrolizumab Experimental Treatment 2 Interventions

Route: IV Infusion Frequency: Q3W Dose: 200mg

Who Is Running the Clinical Trial?

Bicara Therapeutics

Lead Sponsor

Trials

2

Recruited

940+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

Pembrolizumab significantly improved progression-free survival (PFS) in patients with unresectable or metastatic microsatellite instability-high (MSI-H) colorectal cancer, with a median PFS of 16.5 months compared to 8.2 months for standard chemotherapy, indicating its efficacy as a first-line treatment.

The FDA found no safety concerns during the approval process, and while both pembrolizumab and standard of care had similar adverse reactions, the duration of treatment with pembrolizumab was nearly double that of standard care, suggesting a potentially more favorable treatment profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the First-line Treatment of Patients with MSI-H/dMMR Advanced Unresectable or Metastatic Colorectal Carcinoma. Casak, SJ., Marcus, L., Fashoyin-Aje, L., et al.[2022]

In a phase II trial involving 159 patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma, pembrolizumab showed significant antitumor activity, with an objective response rate of 50.0% in the locally advanced cohort and 35.2% in the recurrent/metastatic cohort.

The treatment demonstrated a manageable safety profile, with only 11.9% of patients experiencing grade 3-5 treatment-related adverse events, indicating that pembrolizumab is a promising and durable treatment option for cSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial. Hughes, BGM., Munoz-Couselo, E., Mortier, L., et al.[2022]

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

In a study of 38 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, the median overall survival was 11.08 months, indicating that the drug is a viable treatment option for this patient group.

The study found that while pembrolizumab's effectiveness in real-life settings appears lower than in clinical trials, it still provides significant benefits, particularly for patients with high PD-L1 expression, and highlights the importance of monitoring for immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world efficacy and safety of pembrolizumab in patients with non-small cell lung cancer: a retrospective observational study. Cavaille, F., Peretti, M., Garcia, ME., et al.[2022]

In a real-life study of 108 patients with advanced non-small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score of ≥50%, pembrolizumab showed a median progression-free survival of 10.1 months, similar to results from the KEYNOTE-024 trial.

The treatment was generally well-tolerated, with only 8% of patients experiencing grade 3 adverse events, and no severe (grade 4 or 5) adverse events reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab for non-small cell lung cancer patients with PD-L1 ≥50% in a multicenter real-life cohort: The PEMBREIZH study. Amrane, K., Geier, M., Corre, R., et al.[2021]

Pembrolizumab, an anti-PD-1 antibody, has been approved for treating unresectable or metastatic melanoma, especially in patients who have progressed after ipilimumab treatment, marking a significant advancement in immuno-oncology.

The drug has also received breakthrough status for treating non-small cell lung cancer (NSCLC) that is EGFR mutation-negative and ALK rearrangement-negative, indicating its broad potential in cancer therapy, with ongoing trials to explore its use in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab. Khoja, L., Butler, MO., Kang, SP., et al.[2022]

The phase I trial of MEDI5752, a bispecific antibody that targets both PD-1 and CTLA4, shows that the drug is well tolerated by patients.

Preliminary results indicate that MEDI5752 is active in treating various tumor types, with durable responses observed, suggesting potential effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

Pembrolizumab (P) can be safely combined with various chemotherapy agents, including gemcitabine and liposomal doxorubicin, in patients with advanced solid tumors, as shown in a phase Ib trial involving 49 patients.

The combination treatment resulted in eight partial responses across different tumor types, indicating potential efficacy, but further studies are needed to confirm if the response duration is better than chemotherapy or immunotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). Weiss, GJ., Waypa, J., Blaydorn, L., et al.[2022]

A 45-year-old male with metastatic melanoma experienced severe immune-related adverse events from ipilimumab, leading to its discontinuation, but successfully transitioned to pembrolizumab.

After over 20 months of treatment with pembrolizumab, the patient has shown no major toxicities and has achieved an ongoing partial response, suggesting that pembrolizumab may be a safe and effective option for patients with prior severe adverse events from other immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in a BRAF-mutant metastatic melanoma patient following a severe immune-related adverse event with ipilimumab. Aya, F., Fernández-Martínez, A., Gaba, L., et al.[2017]

Citations

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Phase 2/3 Trial Further Evaluates Ficerafusp Alfa With ... Those are poor prognosis lesions, and although patients had those relatively adverse tumor features, we saw an ORR of 54%. Of the patients who ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.4

Preliminary phase 1/1b dose expansion results of the ... In KN-158, pembrolizumab (P) was reported to have an ORR of 10%, DCR of 25%, and a 12-month PFS rate of 15% in patients with incurable SCAC.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40643947/

Phase I clinical trial of the bifunctional EGFR/TGF-β fusion ... With combination therapy, 4/13 evaluable patients (31%) had a confirmed response, including one with head and neck squamous cell carcinoma ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06788990

FORTIFI-HN01: A Study of Ficerafusp Alfa (BCA101) or ... This study intends to evaluate the safety and efficacy of ficerafusp alfa in combination with pembrolizumab versus placebo with pembrolizumab in 1L PD-L1- ...

5. cancernetwork.com cancernetwork.com/view/ficerafusp-alfa-pembrolizumab-receives-fda-btd-in-front-line-hnscc

Ficerafusp Alfa/Pembrolizumab Receives FDA BTD in ... Of confirmed responders, 80% (n = 12 of 15) achieved at least 80% tumor shrinkage; the complete response rate was 21%, and the disease control ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6017

Ficerafusp alfa with pembrolizumab in patients ... Safety findings were consistent with the known safety profile of ficerafusp alfa plus pembrolizumab, while pharmacodynamic analyses demonstrated ...

7. onclive.com onclive.com/view/ficerafusp-alfa-pembrolizumab-demonstrates-clinically-meaningful-activity-in-metastatic-hnscc

Ficerafusp Alfa/Pembrolizumab Demonstrates Clinically ... Ficerafusp alfa (BCA101) in combination with pembrolizumab (Keytruda) demonstrated clinically meaningful anti-tumor activity for the first-line treatment of ...

8. aacrjournals.org aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-25-0100/763868/Phase-I-Clinical-Trial-of-the-Bifunctional-EGFR

Phase I Clinical Trial of the Bifunctional EGFR/TGF-β Fusion ... Conclusions: Ficerafusp alfa exhibited a manageable safety profile and clinical activity as monotherapy and in combination with pembrolizumab, with exposure ...