CX-801 + Pembrolizumab for Advanced Solid Tumors

Recruiting at 1 trial location

Overseen By Karen Deane

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: CytomX Therapeutics

Must not be taking: Immunotherapy, Investigational drugs

Disqualifiers: CNS involvement, Serious illness, others

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

Compensation: Varies

Number of Visits: Unknown

121 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this first-in-human study, CTMX-801-101, is to characterize the safety, tolerability, and antitumor activity of CX-801 as monotherapy and in combination with pembrolizumab in adult participants with advanced solid tumors.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does require that you have not had any systemic anticancer treatment or investigational drugs within 4 weeks before starting the study treatment.

What data supports the effectiveness of the drug CX-801 + Pembrolizumab for advanced solid tumors?

Pembrolizumab, one of the drugs in the treatment, has shown effectiveness in improving survival rates in patients with advanced non-small-cell lung cancer and melanoma by helping the immune system fight cancer cells. Additionally, high-dose interferon-alpha 2b, similar to CX-801, is used in treating melanoma, suggesting potential benefits in modulating the immune response. ^{1 2 3 4 5}

Is the combination of CX-801 and Pembrolizumab safe for humans?

High-dose interferon-alpha 2b, which is related to CX-801, has been used in treatments for melanoma and has shown some safety concerns, such as the development of antibodies in some patients. However, specific safety data for the combination of CX-801 and Pembrolizumab is not provided in the available research. ^{2 6 7 8 9}

What makes the drug CX-801 + Pembrolizumab unique for treating advanced solid tumors?

CX-801 is a novel treatment that combines a dually-masked interferon alpha-2b with pembrolizumab, an immune checkpoint inhibitor. This combination aims to enhance the immune system's ability to target and destroy cancer cells, potentially offering a new approach for patients with advanced solid tumors. ^{1 10 11 12 13}

Research Team

Monika Vainorius, MD

Principal Investigator

CytomX Therapeutics

Eligibility Criteria

This trial is for adults with advanced solid tumors. It's the first time they're testing CX-801, alone and combined with pembrolizumab. Participants should meet certain health conditions but specific inclusion and exclusion criteria are not provided.

Inclusion Criteria

My organs are working well.

My cancer has spread and cannot be removed by surgery, and it has gotten worse after treatment.

Measurable disease per RECIST v1.1

Exclusion Criteria

I haven't used any experimental drugs or devices in the last 4 weeks.

Serious concurrent illness

I have had a different cancer than my current one in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

CX-801 dose escalation to identify the maximum tolerated dose (MTD) as monotherapy and in combination with pembrolizumab

44 months

Dose Expansion

Further assessment of safety, tolerability, and preliminary antitumor activity of CX-801 combination therapy in indication-specific expansion cohorts

44 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 months

Treatment Details

Interventions

• CX-801
• Pembrolizumab

Trial Overview The study tests the safety and cancer-fighting ability of a new treatment, CX-801, on its own and paired with pembrolizumab, which is already used in cancer therapy.

Participant Groups

Group I: CX-801 + pembrolizumab Experimental Treatment 2 Interventions

Group II: CX-801 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

CytomX Therapeutics

Lead Sponsor

Trials

9

Recruited

1,000+

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

Findings from Research

Pembrolizumab, an immunotherapy for advanced non-small-cell lung cancer (NSCLC), significantly improves progression-free and overall survival compared to traditional chemotherapy, with fewer side effects, particularly in patients with high PD-L1 expression (≥50%).

In combination with pemetrexed and carboplatin, pembrolizumab also enhances treatment effectiveness and maintains manageable toxicity, leading to a shift in first-line treatment strategies for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. Reck, M.[2018]

In a study of 22 melanoma patients receiving high-dose interferon-alpha 2b, baseline levels of regulatory T cells (Tregs) were significantly higher compared to healthy individuals, suggesting a potential link between Treg levels and melanoma progression.

While there was a trend towards reduced Treg levels after treatment with interferon-alpha 2b, this change was not statistically significant, indicating that further research is needed to understand the role of Tregs in treatment response and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulatory T cell frequency in patients with melanoma with different disease stage and course, and modulating effects of high-dose interferon-alpha 2b treatment. Ascierto, PA., Napolitano, M., Celentano, E., et al.[2021]

In a phase I study involving 113 patients with advanced solid tumors, MK-4166 was found to be tolerable, with only 8% of patients experiencing treatment-related grade ≥3 adverse events and no treatment-related deaths reported.

The combination of MK-4166 with pembrolizumab showed promising efficacy, particularly in patients with immune checkpoint inhibitor (ICI)-naïve melanoma, achieving an objective response rate of 62%, indicating potential for effective treatment in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of MK-4166, an Anti-human Glucocorticoid-Induced TNF Receptor Antibody, Alone or with Pembrolizumab in Advanced Solid Tumors. Papadopoulos, KP., Autio, K., Golan, T., et al.[2022]

In a study of 268 advanced NSCLC cases, using the maximum PD-L1 expression value from multiple core biopsies improved the accuracy of determining PD-L1 status compared to whole tumor sections, with four cores needed for a 1% cutoff and three for a 50% cutoff.

The study found that fewer than three cores were insufficient for reliably identifying tumors with high PD-L1 expression (≥50%), highlighting the importance of adequate sampling for effective patient selection for pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Expression Heterogeneity in Non-Small Cell Lung Cancer: Defining Criteria for Harmonization between Biopsy Specimens and Whole Sections. Munari, E., Zamboni, G., Lunardi, G., et al.[2019]

Pembrolizumab, an anti-PD-1 antibody, has shown significant promise in treating advanced melanoma by blocking the PD-1 pathway, which inhibits immune responses against tumors.

This immunotherapeutic strategy not only demonstrates efficacy in advanced melanoma but also shows potential clinical responses in various other solid and blood cancers, highlighting its broad applicability in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of melanoma. Kumar, SS., McNeil, CM.[2015]

In a clinical trial involving 31 high-risk melanoma patients treated with recombinant interleukin-2 and recombinant interferon-alpha 2b, 36% developed antibodies against interferon-alpha, with 27% of those having neutralizing capabilities that could affect treatment efficacy.

Patients with neutralizing antibodies showed significantly lower levels of beta 2-microglobulin and soluble IL-2 receptor, suggesting that monitoring these immunological markers could help identify patients who may need alternative treatments if their response to interferon therapy is compromised.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant immunotherapy in malignant melanoma: impact of antibody formation against interferon-alpha on immunoparameters in vivo. Davis-Daneshfar, A., Böni, R., von Wussow, P., et al.[2019]

Administration of human recombinant interferon-alpha-2b (IFN) significantly enhances tumor blood flow in tumor-bearing mice within 30 minutes, which may improve the delivery of radiolabeled antibodies to tumors.

Histological analysis shows that IFN does not induce inflammatory changes in tumors 72 hours after administration, suggesting that its effects on tumor perfusion are not associated with increased inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of biological response modifiers: measurement of tumor blood flow and temperature. Li, J., Merton, DA., Thakur, ML., et al.[2018]

Patients with metastatic melanoma receiving a combination of interferon-α-2b and interleukin-2 along with chemotherapy showed a significantly higher overall response rate compared to those receiving chemotherapy alone (P=0.027).

The combination therapy also resulted in a notably improved overall survival rate (P=0.029) without increasing the incidence of adverse reactions, indicating a safer treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of interferon-α-2b and interleukin-2 combined with chemotherapy in metastatic melanoma. Su, Z., Shi, F., Zhang, J., et al.[2020]

High-dose pegylated interferon α-2b was well-absorbed in 32 patients with high-risk melanoma, showing a median time to peak concentration of 24 hours and a half-life of 43 to 51 hours, indicating effective drug delivery.

The treatment demonstrated acceptable safety with side effects consistent with previous studies, and the pharmacokinetic/pharmacodynamic model provided insights into predicting hematologic toxicity related to the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic/pharmacodynamic analysis of adjuvant pegylated interferon α-2b in patients with resected high-risk melanoma. Daud, AI., Xu, C., Hwu, WJ., et al.[2021]

A 70-year-old woman developed immune checkpoint inhibitor (ICI)-related myocarditis and new-onset myasthenia gravis (MG) after starting pembrolizumab for metastatic thymic cancer, highlighting potential serious side effects of this treatment.

Despite the adverse effects, the patient showed significant improvement in her metastatic disease after 6 weeks, indicating that pembrolizumab can be effective in reducing tumor burden even in the presence of severe immune-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint inhibitor-induced myocarditis and myasthenia gravis in a recurrent/metastatic thymic carcinoma patient: a case report. Szuchan, C., Elson, L., Alley, E., 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]

In a study of 655 patients with advanced melanoma, pembrolizumab showed an overall objective response rate of 33%, indicating its efficacy in treating this type of cancer.

The median overall survival for patients receiving pembrolizumab was 23 months, with a 12-month survival rate of 66%, while 14% of patients experienced severe treatment-related adverse events, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. Ribas, A., Hamid, O., Daud, A., et al.[2022]

Nivolumab and pembrolizumab are monoclonal antibodies that work by blocking the PD-1 receptor, which helps to enhance the body's immune response against tumors.

Both drugs have been recently approved for treating metastatic melanoma, with nivolumab also approved for non-small cell lung cancer, indicating their efficacy in targeting these specific cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 Blockers. Wolchok, JD.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Regulatory T cell frequency in patients with melanoma with different disease stage and course, and modulating effects of high-dose interferon-alpha 2b treatment. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Phase I Study of MK-4166, an Anti-human Glucocorticoid-Induced TNF Receptor Antibody, Alone or with Pembrolizumab in Advanced Solid Tumors. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

PD-L1 Expression Heterogeneity in Non-Small Cell Lung Cancer: Defining Criteria for Harmonization between Biopsy Specimens and Whole Sections. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of melanoma. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Adjuvant immunotherapy in malignant melanoma: impact of antibody formation against interferon-alpha on immunoparameters in vivo. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Influence of biological response modifiers: measurement of tumor blood flow and temperature. [2018]

8. Italy pubmed.ncbi.nlm.nih.gov

Effect of interferon-α-2b and interleukin-2 combined with chemotherapy in metastatic melanoma. [2020]

9. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetic/pharmacodynamic analysis of adjuvant pegylated interferon α-2b in patients with resected high-risk melanoma. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Checkpoint inhibitor-induced myocarditis and myasthenia gravis in a recurrent/metastatic thymic carcinoma patient: a case report. [2022]

11. England 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. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

PD-1 Blockers. [2022]