JAB-21822 + Cetuximab for Solid Tumors

Not currently recruiting at 3 trial locations

Overseen By Ramina Mikailova

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Jacobio Pharmaceuticals Co., Ltd.

Disqualifiers: Brain metastases, Active infection, HBV, HCV, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, JAB-21822, both alone and with Cetuximab (a monoclonal antibody therapy), to assess its safety and effectiveness for individuals with advanced solid tumors that have the KRAS G12C mutation. The goal is to evaluate the treatments' efficacy against these cancers and determine the optimal dose. The trial seeks participants with a solid tumor carrying the KRAS G12C mutation, who have tried at least one other treatment, and have measurable tumors. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative therapy.

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

The trial protocol does not specify if you need to stop your current medications. However, since the trial involves new treatments, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for specific guidance.

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

Previous studies found JAB-21822, also known as glecirasib, to be generally safe. Patients experienced side effects, but these were usually mild and similar to those from other treatments. The most common side effects affected the digestive system, such as nausea or diarrhea, but they were typically not severe.

When combined with cetuximab, JAB-21822 was also well-tolerated. Serious side effects were uncommon, and researchers found the safety manageable. This means that while some side effects occurred, they were expected and not too concerning.

Overall, both JAB-21822 alone and with cetuximab have been well-tolerated in studies so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for metastatic colorectal cancer (mCRC), which typically include chemotherapy and biologics, JAB-21822 is being explored for its novel approach. This drug is unique because it targets specific pathways involved in cancer cell growth with a new mechanism of action, aiming to enhance effectiveness. Additionally, when combined with Cetuximab, JAB-21822 could potentially improve outcomes by working synergistically to inhibit tumor growth more effectively than existing therapies. Researchers are excited about the potential for JAB-21822 to offer a more targeted treatment option, possibly leading to better responses and fewer side effects for patients.

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

Research has shown that JAB-21822, also known as glecirasib, yields promising results for treating tumors with the KRAS G12C mutation. One study found that 50.9% of patients responded positively to JAB-21822 alone, with significant tumor shrinkage. In this trial, some participants will receive JAB-21822 as monotherapy to assess its effectiveness. Others will receive a combination of JAB-21822 with cetuximab, which previous studies have shown to produce even better results for those with advanced colorectal cancer. This suggests that using both drugs together might be more effective than using JAB-21822 alone. Overall, these findings offer hope for people dealing with certain types of advanced cancers. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that have a specific mutation called KRAS G12C can join this trial. They must have tried at least one standard treatment before, be able to take pills, and their organs need to work well. People with brain or spinal metastases, active infections, certain heart conditions, or unresolved severe side effects from previous treatments cannot participate.

Inclusion Criteria

I can swallow and keep down pills.

My cancer has a KRAS G12C mutation.

Must have at least 1 measurable lesion per RECIST v1.1

Exclusion Criteria

My brain or spinal cancer has been treated and stable for at least 28 days.

QT interval >470 msec

Experiencing unresolved CTCAE 5.0 Grade >1 toxicities

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation of JAB-21822 will be administered alone to determine the MTD and RP2D

Up to 4 years

Dose Expansion

Evaluate preliminary antitumor activity when JAB-21822 is administered alone and in combination with cetuximab

Up to 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• JAB-21822

Trial Overview The trial is testing JAB-21822 alone and in combination with Cetuximab in patients. Both drugs target different parts of the cancer cells' growth mechanisms. The goal is to see how safe they are and how well patients tolerate them.

How Is the Trial Designed?

Group I: Experimental: Arm B, JAB-21822 combination with Cetuximab, Phase 2, Dose Expansion Experimental Treatment 2 Interventions

JAB-21822 will be administered together with Cetuximab in mCRC patients to evaluate the preliminary antitumor activity.

Group II: Arm A1, JAB-21822 monotherapy, Phare 2, Dose Expansion Experimental Treatment 1 Intervention

JAB-21822 will be administered alone at RP2D in selected cancer type patients to evaluate the preliminary antitumor activity.

Group III: Arm A0, JAB-21822 monotherapy, Phase 1, Dose Escalation Experimental Treatment 1 Intervention

Dose escalation of JAB-21822 will be administered alone to determine the MTD and RP2D

JAB-21822 is already approved in European Union, United States for the following indications:

Approved in European Union as Glecirasib for:

• Pancreatic cancer

Approved in United States as Glecirasib for:

• Pancreatic cancer

Who Is Running the Clinical Trial?

Jacobio Pharmaceuticals Co., Ltd.

Lead Sponsor

Trials

21

Recruited

2,300+

Published Research Related to This Trial

Cetuximab, an antibody targeting the EGFR, effectively triggers antibody-dependent cellular cytotoxicity (ADCC) against lung cancer cells, even at low concentrations, indicating its potential as an immunotherapy.

The study found that ADCC activity is significantly enhanced by interleukin-2, particularly through the activation of natural killer (NK) cells, and is less affected by chemotherapy, suggesting a robust immunologic mechanism for cetuximab in treating lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines. Kurai, J., Chikumi, H., Hashimoto, K., et al.[2022]

Cetuximab is an effective treatment for patients with metastatic colorectal cancer (mCRC) who have wild-type KRAS, and its use has been supported by various clinical trials assessing its impact on patient outcomes and quality of life.

The identification of KRAS mutation status is crucial for selecting patients who are most likely to benefit from cetuximab, enhancing the treatment's efficacy in managing unresectable mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of cetuximab in current treatment of metastatic colorectal cancer. Sotelo Lezama, MJ., Sastre Valera, J., Díaz-Rubio García, E.[2018]

Steroid treatment, specifically dexamethasone, significantly inhibits the antibody-dependent cellular cytotoxicity (ADCC) activity of natural killer (NK) cells when used with the anti-EGFR antibody cetuximab, which is important for treating solid tumors like head and neck squamous cell carcinoma and colon cancer.

Dexamethasone also reduces the expression of activation markers on NK cells, suggesting that while steroids are used to prevent side effects of anti-EGFR therapy, they may negatively impact the effectiveness of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the change in cetuximab-induced antibody-dependent cellular cytotoxicity activity of natural killer cells by steroid. Kumai, T., Oikawa, K., Aoki, N., et al.[2022]

KRAS mutations in colorectal cancer (CRC) are linked to resistance against cetuximab, but combining cetuximab with dasatinib can enhance the drug's effectiveness against KRAS mutant tumors, as shown in both in vitro and in vivo studies.

The combination treatment led to decreased cell proliferation and increased apoptosis in KRAS mutant tumors, suggesting that dasatinib alters key signaling pathways, making these tumors more responsive to cetuximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab. Dunn, EF., Iida, M., Myers, RA., et al.[2022]

Cetuximab, a treatment for advanced colorectal cancer, can cause severe infusion reactions, including loss of consciousness, but therapy can be continued safely with proper management.

In two observed cases, patients experienced serious reactions but were successfully treated with corticosteroids and monitored in the intensive care unit, demonstrating that cetuximab can still provide therapeutic benefits even after such reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful management of infusion reaction accompanying the start of cetuximab therapy. Melichar, B., Cerman, J., Malírová, E.[2018]

Cetuximab demonstrated antitumor activity in patients with metastatic colorectal carcinoma (CRC) who were resistant to standard treatments, achieving a response rate of approximately 12.4% in a study of 346 patients.

The treatment was generally well tolerated, with a high incidence of acneiform rash (82.9%), which correlated with better treatment efficacy, while EGFR mutations and gene amplification did not significantly influence the response to cetuximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. Lenz, HJ., Van Cutsem, E., Khambata-Ford, S., et al.[2022]

In a study of 226 patients with advanced colorectal cancer treated with cetuximab, EGFR gain was associated with better treatment outcomes, indicating that higher levels of EGFR may enhance the drug's efficacy.

PTEN protein expression was linked to longer time to progression in patients with wild-type KRAS, especially those with elevated amphiregulin levels, suggesting that maintaining PTEN function could be crucial for optimizing cetuximab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EGFR gene gain and PTEN protein expression are favorable prognostic factors in patients with KRAS wild-type metastatic colorectal cancer treated with cetuximab. Razis, E., Pentheroudakis, G., Rigakos, G., et al.[2022]

Cetuximab combined with chemotherapy shows a good overall response rate (43.1%) and overall survival (28.5 months) in patients with advanced colorectal cancer and unclear K-ras status, based on a study of 102 patients.

The treatment is considered safe, with common side effects including acneiform eruptions and neutropenia, but no treatment-related deaths were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of cetuximab combined with chemotherapy for patients with advanced colorectal cancer and unclear K-ras status]. Guo, GF., Xia, LP., Qiu, HJ., et al.[2018]

HLX07, a re-engineered version of cetuximab, maintains similar binding affinity to EGFR but demonstrates improved bioactivity and reduced toxicity in preclinical studies, suggesting it may be a more effective treatment option.

In a preliminary phase 1 study, HLX07 showed a lower incidence of severe skin rashes compared to cetuximab, indicating a potential for better tolerability in patients undergoing EGFR-targeted therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distinguishing features of a novel humanized anti-EGFR monoclonal antibody based on cetuximab with superior antitumor efficacy. Lin, PH., Tseng, CL., Cheng, YC., et al.[2022]

The combination of divarasib and cetuximab in treating KRAS G12C-positive colorectal cancer showed a manageable safety profile, with only 13.8% of patients experiencing treatment-related adverse events that required dose reductions, and no treatment withdrawals.

This combination therapy demonstrated promising antitumor activity, achieving a 62.5% objective response rate in previously untreated patients, with a median progression-free survival of 8.1 months, indicating its potential effectiveness in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial. Desai, J., Alonso, G., Kim, SH., et al.[2023]

Cetuximab has demonstrated significant efficacy in treating metastatic colorectal cancer, achieving a partial response in 10.8% of patients receiving it alone and 22.9% when combined with irinotecan, based on a Phase III trial involving 329 patients.

The drug is generally well tolerated, with common side effects like acnelike rash and hypersensitivity reactions, but the lack of reliable predictive markers for patient selection remains a challenge for its clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer. Wong, SF.[2022]

The combination of cetuximab and cisplatin was found to be safe for women with advanced cervical cancer, with manageable side effects, but did not show improved tumor response compared to cisplatin alone, as only 9% and 16% of patients responded in the prior chemotherapy and no chemotherapy groups, respectively.

EGFR protein was expressed in 98% of the tumors analyzed, suggesting that while the treatment was tolerated, the expected benefit from targeting EGFR with cetuximab was not realized in terms of enhanced efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of cisplatin plus cetuximab in advanced, recurrent, and previously treated cancers of the cervix and evaluation of epidermal growth factor receptor immunohistochemical expression: a Gynecologic Oncology Group study. Farley, J., Sill, MW., Birrer, M., et al.[2021]

Cetuximab shows modest efficacy as a single-agent treatment for metastatic colorectal cancer (CRC) in patients without KRAS mutations, and it can improve overall and progression-free survival when combined with irinotecan in first-line therapy.

The identification of KRAS mutations serves as a negative predictive biomarker, helping to avoid unnecessary toxicity in patients who are unlikely to benefit from cetuximab, thus enhancing the drug's clinical utility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in the treatment of patients with colorectal cancer. Garrett, CR., Eng, C.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41037823/

Efficacy and safety of glecirasib in solid tumors with KRAS ... Of the 53 efficacy-evaluable patients, the confirmed ORR was 50.9% (95% confidence interval [CI], 36.8%-64.9%), with an ORR of 46.9% (95% CI, ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.191

Efficacy and safety of glecirasib (JAB-21822) monotherapy ... Glecirasib in combination with cetuximab demonstrated better efficacy compared with glecirasib monotherapy in advanced KRAS G12C mutated advanced CRC.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3008

Updated safety and efficacy data of combined KRAS G12C ... Preliminary activity and safety results of KRAS G12C inhibitor glecirasib (JAB-21822) in patients with pancreatic cancer and other solid tumors.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05009329

NCT05009329 | A Study of JAB-21822 in Adult Patients ... To assess safety, tolerability, PK, efficacy and determine recommended phase 2 dose (RP2D) of JAB-21822 (glecirasib) administered in adult participants with ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT454372

Updated safety and efficacy data of combined KRAS G12C ... Preliminary activity and safety results of KRAS G12C inhibitor glecirasib (JAB-21822) in patients with pancreatic cancer and other solid tumors. First ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05009329

NCT05009329 | A Study of JAB-21822 in Adult Patients ... To assess safety, tolerability, PK, efficacy and determine recommended phase 2 dose (RP2D) of JAB-21822 (glecirasib) administered in adult participants with ...