ASP8374 + Cemiplimab for Recurrent Brain Cancer

Recruiting at 3 trial locations

Overseen By David Reardon, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Anti-VEGF, Immunosuppressants

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, others

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

Compensation: Varies

Number of Visits: 7

14 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there are specific time periods that must pass after certain treatments before starting the study, such as 4 weeks from cytotoxic therapy and 6 weeks from antibodies. It's best to discuss your current medications with the study team to understand how they might affect your eligibility.

What data supports the effectiveness of the drug combination ASP8374 and Cemiplimab for recurrent brain cancer?

Cemiplimab has shown effectiveness in treating other cancers, such as advanced non-small-cell lung cancer and cervical cancer, by blocking a protein that helps cancer cells hide from the immune system. This suggests it might also help in treating brain cancer when combined with other treatments. ^{1 2 3 4 5}

Is the treatment ASP8374 + Cemiplimab generally safe for humans?

Cemiplimab, also known as Libtayo, has been shown to have an acceptable safety profile in clinical trials for various cancers, including advanced cutaneous squamous cell carcinoma and cervical cancer. Most side effects were manageable with appropriate treatment or by stopping the medication, and serious side effects were relatively rare. ^{2 6 7 8 9}

What makes the drug combination ASP8374 and Cemiplimab unique for treating recurrent brain cancer?

ASP8374 and Cemiplimab is a novel combination for recurrent brain cancer, potentially offering a new approach by combining an immune checkpoint inhibitor (Cemiplimab) with another agent (ASP8374), which may enhance the immune system's ability to fight cancer cells, unlike traditional treatments that often target specific cancer growth pathways. ^{4 10 11 12 13}

What is the purpose of this trial?

This trial is testing the safety and effectiveness of combining two drugs, ASP8374 and cemiplimab, for people with recurrent brain cancer. The study aims to find the best dose and see if the combination helps before surgery. The drugs work by boosting the immune system to fight cancer cells. Cemiplimab has been previously tested in combination with other treatments for severe cancers.

Research Team

David A Reardon, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults over 18 with recurrent malignant glioma, either WHO grade IV GBM or variants, or grade III (Cohort 1 only). They must have a Karnofsky performance status of ≥70 and show tumor progression. Participants need adequate organ function and should be at their first or second relapse after radiotherapy. Pregnant women and those with certain medical conditions or treatments are excluded.

Inclusion Criteria

I am using or willing to use effective birth control during and for 4 months after the study.

You are willing and able to read and sign a form that says you agree to participate in the trial.

My condition has worsened for the first or second time after improving.

Exclusion Criteria

Pregnant, breastfeeding, or expecting to conceive within the projected duration of the trial

You are currently or planning to participate in a study that involves testing a new drug or medical device.

I have an active tuberculosis infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of ASP8374 when combined with cemiplimab using a 3+3 design

Up to 2 years

Every 3 weeks

Dose Expansion

Participants randomized into treatment groups to receive ASP8374 plus cemiplimab prior to surgery or no therapy prior to surgery

14±5 days prior to surgery

1 visit (in-person)

Post-operative Treatment

All Cohort 2 participants receive ASP8374 plus cemiplimab every 3 weeks at the MTD/RP2D established by Cohort 1

Up to 2 years

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6-12 months

Treatment Details

Interventions

• ASP8374
• Cemiplimab

Trial Overview The study tests the combination of ASP8374 with cemiplimab in two parts: finding the safest high dose (Part 1) and assessing its effect before surgery (Part 2). It aims to establish safety and effectiveness against recurrent brain tumors.

Participant Groups

Group I: ASP8374 and Cemiplimab-Cohort 2 Experimental Treatment 2 Interventions

Upon determination of the MTD/RP2D of ASP8374 plus cemiplimab in Cohort 1, a dose expansion will be performed in which eligible participants who are candidates for surgical resection will enroll to Cohort 2 and will be randomized into one of two treatment groups (2A-2B). Group 2A: IV ASP8374 plus cemiplimab within 14± 5 days prior to surgery at the MTD/RP2D established in Cohort 1. Group 2B: No immune checkpoint therapy prior to surgery. Post-operatively, all Cohort 2 participants will receive ASP8374 plus cemiplimab every 3 weeks administered at the MTD/RP2D established by Cohort 1

Group II: ASP8374 and Cemiplimab-Cohort 1 Experimental Treatment 2 Interventions

A 3+3 dose escalation design will be used to determine maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of ASP8374 when combined with cemiplimab. Participants will receive ASP8374 and Cemiplimab every 3 weeks for up to 2 years. ASP8374 will be available until October 31, 2022. Subjects may continue treatment with cemiplimab alone after that date.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Astellas Pharma Inc

Industry Sponsor

Trials

700

Recruited

236,000+

Headquarters

Tokyo, Japan

Top Products

- Xtandi (enzalutamide) for prostate cancer, - Xospata (gilteritinib) for AML, - Padcev (enfortumab vedotin) for bladder cancer, - Prograf (tacrolimus) for organ rejection prevention

Tadaaki Taniguchi

Astellas Pharma Inc

Chief Medical Officer since 2023

MD, PhD

Naoki Okamura

Astellas Pharma Inc

Chief Executive Officer since 2023

University of Tokyo, Faculty of Pharmacy

Findings from Research

In a phase 3 study involving 710 patients with advanced non-small-cell lung cancer and high PD-L1 expression, cemiplimab significantly improved overall survival (not reached) and progression-free survival (8.2 months) compared to chemotherapy (14.2 months).

Cemiplimab also demonstrated a better safety profile, with fewer grade 3-4 treatment-emergent adverse events (28%) compared to chemotherapy (39%), making it a promising first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Sezer, A., Kilickap, S., Gümüş, M., et al.[2022]

Cemiplimab, administered as monotherapy or in combination with hypofractionated radiation therapy, showed a 10% objective response rate in patients with recurrent or metastatic cervical cancer, particularly in those with squamous histology, indicating its potential efficacy in this subgroup.

The most common side effects were diarrhea, fatigue, and hypokalemia, affecting 35%, 25%, and 25% of patients respectively, suggesting that while cemiplimab has anti-tumor activity, it also has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. Rischin, D., Gil-Martin, M., González-Martin, A., et al.[2021]

In a phase III clinical trial involving 325 patients with recurrent glioblastoma, cediranib did not significantly improve progression-free survival compared to lomustine alone, whether used as a monotherapy or in combination.

Despite not meeting the primary endpoint, cediranib demonstrated some clinical benefits in secondary outcomes, such as delaying neurological deterioration and reducing the need for corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. Batchelor, TT., Mulholland, P., Neyns, B., et al.[2022]

In a phase II clinical trial involving 158 patients with newly diagnosed glioblastoma, cediranib combined with radiation and temozolomide significantly improved 6-month progression-free survival (PFS) to 46.6% compared to 24.5% for the placebo group (P = 0.005).

Although cediranib showed efficacy in prolonging PFS, it was associated with a higher incidence of grade ≥3 adverse events compared to placebo (P = 0.02), and there was no significant difference in overall survival between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma. Batchelor, TT., Won, M., Chakravarti, A., et al.[2023]

Cemiplimab-rwlc is a newly approved PD-1/L1 inhibitor for first-line treatment of metastatic non-small cell lung cancer (NSCLC) without EGFR or ALK mutations, either alone or with chemotherapy.

This review highlights the differences in patient populations studied for cemiplimab compared to other treatments, emphasizing its role in expanding options for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on Cemiplimab-rwlc in the Treatment of Non-Small Cell Lung Cancer (NSCLC): Focus on Patient Selection and Considerations. Ahn, J., Nagasaka, M.[2023]

Cemiplimab-rwlc (Libtayo) is an FDA-approved immunotherapy for advanced cutaneous squamous cell carcinoma (CSCC) that works by blocking the PD-1 receptor, enhancing the immune system's ability to fight tumors.

Clinical trials have shown that cemiplimab is effective in treating CSCC, although common side effects and safety issues were noted, highlighting the need for ongoing research to improve treatment outcomes and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. Ahmed, SR., Petersen, E., Patel, R., et al.[2019]

Cemiplimab is the first FDA-approved treatment for patients with advanced cutaneous squamous cell carcinoma (CSCC) who cannot undergo curative surgery or radiation, demonstrating rapid and substantial antitumor efficacy in phase II clinical trials.

The treatment has an acceptable safety profile, with low rates of treatment discontinuation (7%) and death (3%), although current recommendations are based mainly on phase II data due to the lack of an approved comparator agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab in advanced cutaneous squamous cell carcinoma. Naik, PP.[2022]

Cemiplimab (Libtayo®) is the first approved immunotherapy for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who cannot undergo surgery or radiotherapy, showing a clinically significant objective response rate in the phase II EMPOWER-CSCC 1 trial.

The treatment has a durable effect, with the median duration of response and overall survival not yet reached, and it has an acceptable safety profile, with manageable immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: A Review in Advanced Cutaneous Squamous Cell Carcinoma. Lee, A., Duggan, S., Deeks, ED.[2020]

In a phase II trial involving 57 patients with recurrent glioblastoma, gefitinib was found to be well tolerated, with mild adverse effects primarily consisting of skin reactions and diarrhea, and only 6% of patients withdrawing due to drug-related side effects.

Despite no objective tumor responses observed, gefitinib showed some activity with a 6-month event-free survival rate of 13% and a median overall survival of 39.4 weeks, suggesting potential benefits that warrant further investigation at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of gefitinib in recurrent glioblastoma. Rich, JN., Reardon, DA., Peery, T., et al.[2022]

In a phase Ib/II study involving 35 patients with recurrent glioblastoma, the maximum tolerable dose (MTD) of the pan-PI3K inhibitor buparlisib was established at 100 mg per day when combined with carboplatin, showing a consistent safety profile without new safety concerns.

However, the combination of buparlisib with either carboplatin or lomustine did not demonstrate sufficient antitumor activity compared to historical data for these single-agent treatments, indicating limited efficacy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buparlisib plus carboplatin or lomustine in patients with recurrent glioblastoma: a phase Ib/II, open-label, multicentre, randomised study. Rosenthal, M., Clement, PM., Campone, M., et al.[2021]

References

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

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. [2022]

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

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. [2021]

3. Greece pubmed.ncbi.nlm.nih.gov

Treatment of recurrent malignant supratentorial astrocytomas with carboplatin and etoposide combined with recombinant mutant human tumor necrosis factor-alpha. [2013]

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

Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. [2022]

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

NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on Cemiplimab-rwlc in the Treatment of Non-Small Cell Lung Cancer (NSCLC): Focus on Patient Selection and Considerations. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. [2019]

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

Cemiplimab in advanced cutaneous squamous cell carcinoma. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Cemiplimab: A Review in Advanced Cutaneous Squamous Cell Carcinoma. [2020]

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

Phase II trial of gefitinib in recurrent glioblastoma. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Dual Targeting of EGFR and MTOR Pathways Inhibits Glioblastoma Growth by Modulating the Tumor Microenvironment. [2023]

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

Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme. [2022]

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

Buparlisib plus carboplatin or lomustine in patients with recurrent glioblastoma: a phase Ib/II, open-label, multicentre, randomised study. [2021]