MQ710 + Pembrolizumab for Solid Tumor Cancers

Recruiting at 6 trial locations

Overseen By Anthony Rossi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Antivirals, Steroids, Anticoagulants, others

Disqualifiers: Active infections, Cardiovascular disease, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

5 Participants Needed

Trial Summary

What is the purpose of this trial?

Participants of this study will have a diagnosis of a solid tumor cancer that has come back to its original location or spread beyond its original location (advanced), came back (relapsed) or worsened (refractory) after standard treatments, or no standard treatments are available for the participants' cancer. The purpose of this study if to find the highest dose of MQ710 that causes few or mild side effects in participants with a solid tumor cancer diagnosis.

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 must stop any prior non-immunotherapy cancer treatments at least 4 weeks before joining, and if you have been on anti-PD1/-PDL1 therapy, a 3-week break is required for some parts of the trial. Please discuss your specific medications with the trial team.

What data supports the effectiveness of the drug MQ710 + Pembrolizumab for solid tumor cancers?

Pembrolizumab has shown promising results in treating various cancers, including non-small cell lung cancer and advanced solid tumors with specific genetic features, by improving survival and demonstrating antitumor activity. ^{1 2 3 4 5}

What safety data exists for Pembrolizumab (KEYTRUDA) in humans?

Pembrolizumab has been studied in various cancers like prostate cancer, osteosarcoma, and skin cancer, showing a manageable safety profile, meaning side effects are generally tolerable for patients. ^{6 7 8 9 10}

What makes the drug MQ710 + Pembrolizumab unique for treating solid tumor cancers?

The combination of MQ710 with pembrolizumab is unique because pembrolizumab is an immune checkpoint inhibitor that helps the immune system attack cancer cells by blocking the PD-1 pathway, which is a mechanism that tumors use to hide from the immune system. This combination may offer a novel approach by potentially enhancing the immune response against solid tumors, although specific details about MQ710's role are not provided in the available research. ^{1 3 11 12 13}

Research Team

Lara Dunn, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with advanced or metastatic solid tumor cancers that have relapsed, worsened after standard treatments, or have no standard treatment options. Eligible participants include those with specific skin cancers and head and neck squamous cell carcinoma who've failed previous therapies including anti-PD-1 therapy (except HNSCC patients with low PD-L1 expression). Participants must be in good enough health to comply with study procedures, not pregnant, willing to use contraception, and free from significant recent medical issues.

Inclusion Criteria

I have a specific type of skin cancer and standard treatments haven't worked for me.

Ability to comply with study procedures in the Investigator's opinion

I am 18 years old or older.

Exclusion Criteria

I have a history of chronic liver disease or cirrhosis.

I have not had an uncontrolled infection in the last 6 months.

I had leukemia (ALL or CLL) or aggressive lymphoma but am in remission and not on immunosuppressive therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of MQ710 following a 3+3 dose escalation scheme

Varies

Dose Expansion

Participants receive MQ710 alone or in combination with pembrolizumab at the MTD/maximally administered dose

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• MQ710
• Pembrolizumab

Trial Overview The study aims to determine the highest dose of MQ710 that can be given safely alongside Pembrolizumab in people with various types of solid tumors. It will involve individuals whose cancer has returned at the original site or spread elsewhere and is resistant to conventional treatments or lacks such options.

Participant Groups

Group I: Dose Expansion Group Experimental Treatment 2 Interventions

MQ710 + pembrolizumab Approximately 8 patients will be recruited into the dose expansion group for monotherapy dosing of MQ710. Approximately 12 patients will be recruited for dosing at the MTD/maximally administered dose established in combination with pembrolizumab.

Group II: Dose Escalation Group Experimental Treatment 1 Intervention

MQ710 The dose levels will be escalated following a standard 3+3 dose escalation scheme.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

In a study involving 1033 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved overall survival compared to docetaxel, with a hazard ratio of 0.66, indicating a 34% reduction in the risk of death.

The effectiveness of pembrolizumab was consistent across both archival and newly collected tumor samples, with better outcomes observed in patients with higher PD-L1 expression (TPS ≥50%), showing hazard ratios of 0.64 and 0.40 for overall survival, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. Herbst, RS., Baas, P., Perez-Gracia, JL., et al.[2023]

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 involving 351 patients with advanced noncolorectal MSI-H/dMMR solid tumors, pembrolizumab showed a significant objective response rate (ORR) of 30.8%, indicating its efficacy in this patient population.

The treatment demonstrated a long median duration of response of 47.5 months and manageable safety, with only 11.1% of patients experiencing severe (grade 3-4) treatment-related adverse events, supporting its use in heavily pretreated cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. Maio, M., Ascierto, PA., Manzyuk, L., et al.[2022]

In a study of 37 patients with unresectable gastric cancer, 8.1% were found to have microsatellite instability-high (MSI-High), which may influence treatment response.

Among 11 patients treated with nivolumab, 75% of those who achieved a partial response were MSI-High, suggesting that anti-PD-1 therapy could be particularly effective for this subgroup of gastric cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Microsatellite Instability in Gastric Cancer]. Choda, Y., Kubota, T., Ishida, M., et al.[2020]

In the phase II KEYNOTE-199 study involving 258 patients with metastatic castration-resistant prostate cancer (mCRPC), pembrolizumab demonstrated modest antitumor activity, with objective response rates of 5% in PD-L1-positive patients and 3% in PD-L1-negative patients, indicating some effectiveness in this challenging population.

The treatment was generally well-tolerated, with 60% of patients experiencing treatment-related adverse events, but only 5% discontinuing due to these events, suggesting that pembrolizumab has an acceptable safety profile while providing encouraging overall survival estimates, particularly in patients with bone-predominant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. Antonarakis, ES., Piulats, JM., Gross-Goupil, M., et al.[2021]

In a phase 2 trial involving 12 patients with advanced osteosarcoma, pembrolizumab showed no clinical benefit at 18 weeks, with all patients experiencing disease progression and a median overall survival of only 6.6 months.

Despite the lack of significant antitumor activity, pembrolizumab was well-tolerated, with no treatment-related deaths or severe adverse events, suggesting it may be safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. Boye, K., Longhi, A., Guren, T., 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]

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]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved quality of life (QOL) compared to chemotherapy, with a notable increase in the global health status score by 6.9 points versus a decrease of 0.9 points for chemotherapy.

Patients treated with pembrolizumab experienced a longer time to deterioration in symptoms like cough and chest pain, with 31% showing deterioration compared to 39% in the chemotherapy group, indicating that pembrolizumab may be a preferable first-line treatment for patients with PD-L1-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Brahmer, JR., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

In a study of 1346 prostate cancer patients, only 3.1% were found to have microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors, indicating that this molecular phenotype is rare but significant for treatment options.

Among 11 patients with MSI-H/dMMR castration-resistant prostate cancer who received anti-PD-1/PD-L1 therapy, 54.5% experienced a significant decline in prostate-specific antigen levels, suggesting that this therapy can be effective for some patients with this specific tumor type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. Abida, W., Cheng, ML., Armenia, J., et al.[2022]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

References

1. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

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

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. [2023]

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

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

[Microsatellite Instability in Gastric Cancer]. [2020]

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

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. [2022]

8. England 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab. [2022]

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

Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. [2022]

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

Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]