Axatilimab + Retifanlimab + Paclitaxel for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: OHSU Knight Cancer Institute

Must not be taking: CYP2C8 inhibitors, CYP3A4 inhibitors

Disqualifiers: Secondary malignancy, Brain metastases, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 2

Duration: 6 months

38 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, you may need to adjust or stop certain drugs, especially those that interact with CYP2C8 and CYP3A4 enzymes, at the recommendation of the trial's pharmacy services.

What data supports the effectiveness of the drug combination Axatilimab, Retifanlimab, and Paclitaxel for cancer?

Research shows that paclitaxel, when combined with other drugs like gemcitabine, significantly improves survival in breast cancer patients compared to using paclitaxel alone. This suggests that paclitaxel can be effective in combination therapies for cancer treatment. ^{1 2 3 4 5}

What makes the drug combination of Axatilimab, Retifanlimab, and Paclitaxel unique for cancer treatment?

This drug combination is unique because it combines Axatilimab, an antibody targeting immune cells, with Retifanlimab, an immune checkpoint inhibitor, and Paclitaxel, a chemotherapy drug, potentially offering a multi-faceted approach to cancer treatment by enhancing the immune response while directly attacking cancer cells. ^{6 7 8 9 10}

What is the purpose of this trial?

This phase I/II trial tests the safety, side effects, and effectiveness of axatilimab in combination with retifanlimab and paclitaxel for the treatment of patients with a solid tumor that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Axatilimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as retifanlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Giving axatilimab in combination with retifanlimab and paclitaxel may be safe, tolerable and/or effective in treating patients with advanced or metastatic solid tumors.

Research Team

Shivaani Kummar, MD

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

This trial is for patients with advanced or metastatic solid tumors. Participants should have a tumor that has spread from its original site to other body parts. Specific eligibility criteria are not provided, but typically include factors like age, health status, and previous treatments.

Inclusion Criteria

Patients with CD4+ T-cell (CD4+) counts ≥ 350 cells/uL are eligible regardless of HIV serology

Corrected QT interval Fridericia's formula (QTcF) of < 480 ms on a 12 lead electrocardiogram (EKG), except for participants with atrioventricular pacemakers or other conditions (e.g., right bundle branch block) that render the QT measurement invalid

Leukocytes ≥ 3,000/mcL

Exclusion Criteria

Secondary malignancy with documented diagnosis by a treating physician < 3 years prior to study day -8. The following criteria also apply: New or progressive brain metastases. Patients with brain metastases not requiring immediate central nervous system (CNS) specific treatment or stable for at least 4 weeks prior to study day -8 are eligible at the discretion of the investigator given that neurologic symptoms are resolved. Patients with active leptomeningeal disease are not eligible. Palliative radiation therapy administered within 1 week prior to study day -8, Note: Participants must have recovered from all radiation-related toxicities (to grade < 1 or baseline), must not require corticosteroids for this purpose, and must not have had radiation pneumonitis. Immunization with a live vaccine within 28 days prior to study day -8. History of organ transplantation, including hematopoietic stem cell transplantation (HSCT). Clinical evidence of interstitial lung disease or active non-infectious pneumonia. Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (≤ 10 mg/day of prednisone or equivalent is permitted). Prior National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 immune-related adverse event (irAE) that required systemic immunosuppression (endocrinopathies managed by stable doses of supplements and/or corticosteroids ≤ 10 mg/day are permitted). Unresolved toxicities (resolution required to grade 1 or baseline) from prior anticancer therapies. The following exceptions apply: Alopecia, lymphopenia, grade 2 neuropathy (if not resulting in functional deficit), and grade 1 (no supplementation required) or grade 2 endocrinopathies (stable on supplements). Prior allergy or severe hypersensitivity reaction to axatilimab, retifanlimab, paclitaxel, cremaphor-containing agents, and/or components of the drug formulations. Active infection requiring systemic antibiotic therapy. Persons of childbearing potential (PCBP) who are pregnant (i.e., positive pregnancy test within 7 days prior to study day -8) or breastfeeding are not eligible. The effects of the investigational regimen on the developing human fetus are unknown. For this reason, persons of reproductive potential must agree to use a highly effective form of contraception, starting with the time of consent to 4 months after the last dose of retifanlimab or 90 days after the last dose of axatilimab, whichever is longer. Sperm-producing participants must not donate sperm throughout the study period and for 90 days post completion of study treatment. Uncontrolled, intercurrent illness and psychiatric illness/social situations that would limit compliance with study requirements, at the discretion of the investigator

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive axatilimab, retifanlimab, and paclitaxel in 28-day cycles, with axatilimab administered on days 8 and 21, retifanlimab on day 1, and paclitaxel on days 1, 8, and 15 of each cycle

6 months

Multiple visits per cycle for drug administration and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits at 30 and 90 days

3 months

2 visits (in-person)

Treatment Details

Interventions

• Axatilimab
• Paclitaxel
• Retifanlimab

Trial Overview The trial is testing the combination of axatilimab, retifanlimab (both monoclonal antibodies), and paclitaxel (a chemotherapy drug) on patients with solid tumors. It aims to see if this mix can safely and effectively stop cancer growth by helping the immune system attack the cancer cells.

Participant Groups

Group I: Treatment (axatilimab, retifanlimab, paclitaxel) Experimental Treatment 8 Interventions

Patients receive axatilimab IV over 30 minutes on day -8, prior to cycle 1. Beginning in cycle 1 day 1, patients receive axatilimab IV over 30 minutes on days 8 and 21 of each cycle, retifanlimab IV over 30-60 minutes on day 1 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy, CT scan, and blood sample collection throughout the study and may undergo MRI and/or PET scan throughout the study.

Axatilimab is already approved in United States for the following indications:

Approved in United States as Axatilimab for:

• Chronic Graft-Versus-Host Disease

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Findings from Research

In a case series of 15 patients with metastatic non-squamous cell lung carcinoma, the combination of paclitaxel and bevacizumab showed a partial response rate of 44% based on CT scans and 65% based on PET scans, indicating potential efficacy in this patient population.

No major toxicity was observed in the treatment, and the median progression-free survival was 4.6 months, suggesting that this regimen is safe and may improve patient outcomes, warranting further investigation in a randomized clinical trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of paclitaxel and bevacizumab in heavily pre-treated non-small-cell lung cancer (NSCLC) patients: a case series study on 15 patients. Le Moulec, S., Hadoux, J., Gontier, E., et al.[2015]

The combination of gemcitabine, epirubicin, and taxol (GET) showed a high overall response rate of 92% in 36 patients with metastatic breast cancer, indicating its potential effectiveness as a front-line treatment.

Despite some significant side effects, including grade 4 neutropenia in 64% of patients, the GET regimen was well tolerated, leading to promising progression-free survival of 21 months and warranting further investigation in randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus epirubicin plus taxol (GET) in advanced breast cancer: a phase II study. Conte, PF., Gennari, A., Donati, S., et al.[2022]

A phase 3 trial involving 529 patients showed that the combination of gemcitabine and paclitaxel significantly improved overall and progression-free survival in metastatic breast cancer compared to paclitaxel alone.

Comparative analysis of three phase 2 studies in East Asian patients indicated no significant ethnic differences in the efficacy and safety of the gemcitabine-paclitaxel regimen, supporting its use as a standard treatment for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consistent efficacy and safety of gemcitabine-paclitaxel in patients with metastatic breast cancer: a retrospective comparison of East Asian and global studies. Xu, B., Zhang, XQ., Chi, HD., et al.[2022]

The combination of gemcitabine and paclitaxel for treating metastatic breast cancer has shown significant improvements in response rates, time to disease progression, and overall survival compared to paclitaxel alone, leading to its approval for this use.

This combination therapy is well tolerated by patients, with no adverse effects on quality of life, making it a promising option for both heavily pretreated and chemotherapy-naive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus paclitaxel in breast cancer. Yardley, DA.[2022]

Paclitaxel (Taxol) has shown promise in Phase I and II trials as a treatment for breast cancer, leading to ongoing investigations into its optimal use.

Current Cooperative Oncology Group trials are exploring various aspects of paclitaxel treatment, including dose intensity, infusion duration, and its combination with other drugs like doxorubicin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of paclitaxel in the treatment of breast cancer: the American Cooperative Group Experience. Sledge, GW.[2015]

Axitinib combined with immune checkpoint inhibitors (ICI) like pembrolizumab or avelumab is now approved for treating advanced renal cell carcinoma, but distinguishing between adverse events (AEs) caused by each treatment is crucial for optimizing therapy.

Experts identified specific AEs such as diarrhea, hepatic toxicity, fatigue, and cardiovascular issues that require unique management strategies when using axitinib-ICI combinations, emphasizing the need for careful clinical monitoring and tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events. Grünwald, V., Voss, MH., Rini, BI., et al.[2021]

Axitinib, when combined with gemcitabine, was well tolerated in patients with advanced pancreatic cancer, showing no dose-limiting toxicities and common side effects like fatigue and hypertension.

In a small group of patients, the combination treatment demonstrated promising antitumor activity, with three out of six evaluable patients achieving confirmed partial responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of axitinib (AG-013736) in combination with gemcitabine in patients with advanced pancreatic cancer. Spano, JP., Moore, MJ., Pithavala, YK., et al.[2022]

In a phase II trial involving 171 patients with metastatic colorectal cancer, axitinib did not show improved progression-free survival compared to bevacizumab when combined with standard chemotherapy regimens (FOLFOX or FOLFIRI).

Axitinib was associated with more grade ≥ 3 adverse events and treatment discontinuations due to side effects, indicating it may be less well tolerated than bevacizumab in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib or bevacizumab plus FOLFIRI or modified FOLFOX-6 after failure of first-line therapy for metastatic colorectal cancer: a randomized phase II study. Bendell, JC., Tournigand, C., Swieboda-Sadlej, A., et al.[2018]

In the phase 3 JAVELIN Renal 101 trial involving 886 treatment-naive patients with advanced renal cell carcinoma, the combination of avelumab and axitinib significantly improved progression-free survival (PFS) compared to sunitinib, with a median PFS of 13.8 months versus 7.0 months for the PD-L1+ population.

While overall survival (OS) data were still immature, the results suggest that avelumab plus axitinib may offer a promising treatment option for patients with advanced renal cell carcinoma, particularly those with PD-L1+ tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma. Choueiri, TK., Motzer, RJ., Rini, BI., et al.[2022]

In a study of 170 patients with advanced non-squamous non-small-cell lung cancer, axitinib combined with pemetrexed and cisplatin showed a higher objective response rate (45.5% and 39.7%) compared to chemotherapy alone (26.3%).

While the combination therapy did not significantly improve progression-free survival compared to chemotherapy alone, it was generally well tolerated, with hypertension being the most common serious side effect in the axitinib groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer. Belani, CP., Yamamoto, N., Bondarenko, IM., et al.[2021]

References

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

Combination of paclitaxel and bevacizumab in heavily pre-treated non-small-cell lung cancer (NSCLC) patients: a case series study on 15 patients. [2015]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Gemcitabine plus epirubicin plus taxol (GET) in advanced breast cancer: a phase II study. [2022]

3. Australia pubmed.ncbi.nlm.nih.gov

Consistent efficacy and safety of gemcitabine-paclitaxel in patients with metastatic breast cancer: a retrospective comparison of East Asian and global studies. [2022]

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

Gemcitabine plus paclitaxel in breast cancer. [2022]

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

Role of paclitaxel in the treatment of breast cancer: the American Cooperative Group Experience. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events. [2021]

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

Phase I study of axitinib (AG-013736) in combination with gemcitabine in patients with advanced pancreatic cancer. [2022]

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

Axitinib or bevacizumab plus FOLFIRI or modified FOLFOX-6 after failure of first-line therapy for metastatic colorectal cancer: a randomized phase II study. [2018]

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

Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma. [2022]

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

Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer. [2021]