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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new treatment combination for individuals with advanced or metastatic solid tumors. The treatment uses three drugs: axatilimab, retifanlimab, and paclitaxel. Axatilimab and retifanlimab are monoclonal antibodies that help the immune system fight cancer, while paclitaxel prevents cancer cells from growing. Individuals diagnosed with a solid tumor that has spread or returned after standard treatment may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

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.

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

Research has shown that combining axatilimab, retifanlimab, and paclitaxel might be safe and manageable for patients with advanced or spreading solid tumors. Early results suggest this treatment can help the body fight cancer cells and stop them from growing and spreading.

Previous studies found that retifanlimab, when used with chemotherapy like paclitaxel, can improve survival and control of tumors. For instance, patients who received retifanlimab with other chemotherapy drugs lived without their cancer worsening for an average of 9.3 months, compared to 7.4 months for those who did not receive retifanlimab. This indicates the treatment is effective in slowing down cancer.

While encouraging safety data exists for treatments similar to this combination, the current trial will provide more detailed information on how well patients handle this specific mix of drugs. Generally, treatments that reach this stage are considered fairly safe, but ongoing research will confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of axatilimab, retifanlimab, and paclitaxel because it offers a fresh approach to treating cancer. Unlike traditional therapies that might focus solely on chemotherapy, this combination includes axatilimab and retifanlimab, which are monoclonal antibodies targeting specific immune checkpoints. Axatilimab works by targeting the CSF-1R pathway, potentially enhancing the body's immune response against cancer cells. Retifanlimab, on the other hand, is a PD-1 inhibitor that helps "wake up" the immune system to better recognize and attack cancer cells. This multi-faceted strategy aims to amplify the effectiveness of paclitaxel, a well-known chemotherapy drug, potentially leading to improved outcomes for patients.

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

This trial will evaluate the combination of axatilimab, retifanlimab, and paclitaxel for cancer treatment. Research has shown that retifanlimab, when used with carboplatin and paclitaxel, can significantly improve survival and control tumor growth in some cancers. In one study, participants taking retifanlimab had a median progression-free survival of 9.3 months, meaning their cancer did not grow during that period, compared to 7.4 months for those taking a placebo. This suggests that retifanlimab can help slow cancer growth. Axatilimab, a monoclonal antibody, is designed to block cancer cells from growing and spreading. Paclitaxel stops cancer cells from dividing, which may help kill them. Together, these treatments could effectively manage advanced or metastatic solid tumors. ^{1 2 4 6 7}

Who Is on the Research Team?

Shivaani Kummar, MD

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

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

Leukocytes ≥ 3,000/mcL

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

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06320405?term=SNDX&rank=7

Study Details | NCT06320405 | Axatilimab in Combination ... It stops cancer cells from growing and dividing and may kill them. Giving axatilimab in combination with retifanlimab and paclitaxel may be safe, tolerable ...

2. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)00631-2/fulltext

Retifanlimab with carboplatin and paclitaxel for locally ... Data from our study demonstrate clinically meaningful improvements in survival and tumour control with retifanlimab plus carboplatin–paclitaxel ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40517007/

Retifanlimab with carboplatin and paclitaxel for locally ... Median progression-free survival was 9·3 months (95% CI 7·5-11·3) in the retifanlimab group and 7·4 months (7·1-7·7) in the placebo group ( ...

4. oncdata.com oncdata.com/retifanlimab-dlwr-approved-for-advanced-squamous-cell-carcinoma-of-the-anal-canal/

Retifanlimab-dlwr Approved for Advanced Squamous Cell ... The results demonstrated a median PFS of 9.3 months in the retifanlimab-dlwr arm versus 7.4 months in the placebo arm. The interim analysis ...

5. onclive.com onclive.com/view/retifanlimab-plus-carboplatin-and-paclitaxel-offers-pfs-benefit-in-recurrent-metastatic-scac

Retifanlimab Plus Carboplatin and Paclitaxel Offers PFS ... Data from the interim overall survival (OS) analysis showed that patients in the retifanlimab arm achieved a median OS of 29.2 months (95% CI, ...

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.3525

POD1UM-303/INTERAACT2 subgroup analyses and ... A consistent PFS benefit in favor of retifanlimab + chemotherapy was observed for all predefined subgroups, including tumors with PD-L1 ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-01397

Axatilimab in Combination with Retifanlimab and Paclitaxel ... It stops cancer cells from growing and dividing and may kill them. Giving axatilimab in combination with retifanlimab and paclitaxel may be safe, tolerable ...