Optimizing Pembrolizumab Therapy With Timing and Intensification With Axitinib

NCT05263609 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: OU-SCC-OPTIMAX
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this research is to test the response of study participants' tumor to pembrolizumab alone, and in combination with axitinib, and to see what effects (good and bad) these drugs have on patients with advanced kidney cancer.

Conditions

Renal Cell Cancer

Keywords

axitinib; pembrolizumab; metastatic renal cell cancer; renal cell cancer

Outcome Measures

Primary Outcomes (2)

• Proportion of Patient Response

  To catalogue the number and proportion of patients with persistence of complete response or optimal partial response at 1 year after the discontinuation of pembrolizumab

  2 year

• Objective Response Rate After Axitinib

  To assess the objective response rate after addition of axitinib in patients with a suboptimal partial response, stable disease or progressive disease on pembrolizumab monotherapy alone.

  2 year

Secondary Outcomes (4)

• Objective Response Rate after Pembrolizumab

  2 year

• Duration of Response

  2 year

• Overall Survival

  2 year

• Proportion of patients that experience toxicity

  2 year

Study Arms (2)

Arm A

EXPERIMENTAL

Arm A (CR/oPR on pembrolizumab monotherapy): Patients will continue pembrolizumab monotherapy if CR/oPR on initial treatment with pembrolizumab monotherapy. If CR/oPR persists at 8 cycles (24 weeks) after assignment on arm A, pembrolizumab break will commence. Patients will be monitored for disease progression with imaging every 9 weeks (+/- 1 week). If patients develop progression, pembrolizumab will be resumed and continued until subsequent PD. At that point, axitinib may be added to pembrolizumab as part of the study or patients may discontinue study treatment per the treating investigator's discretion.

Drug: Pembrolizumab

Arm B

EXPERIMENTAL

Arm B (sPR/SD/PD): Patients with sPR, SD or PD after 6 cycles of pembrolizumab monotherapy will be started on axitinib in addition to continuing pembrolizumab. If patients develop subsequent PD, treatment will be discontinued. If the subsequent scans show SD/PR/CR, the combination treatment will be continued until PD or unacceptable toxicity.

Drug: Axitinib

Interventions

Axitinib DRUG

If pembrolizumab infusions alone do not reduce the patient's tumor size by at least 60%,the patient will be placed in Arm B and start axitinib in addition to continuing pembrolizumab therapy (see Arm B).

Arm B

Pembrolizumab DRUG

If pembrolizumab results in a reduction in tumor size that is greater than 60%, the patient will be placed in Arm A and continue pembrolizumab infusions (see Arm A).

Arm A

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years at the time of consent.
• ECOG performance status ≤1 (Appendix A) within 28 days prior to registration.
• Participants must have histologically or cytologically confirmed clear-cell or non-clear cell renal cell carcinoma.
• Presence of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.137.
• Adequately controlled blood pressure (BP), with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensive medications within 1 week before the Cycle 1/Day 1.
• Willingness of the patient to undergo mandatory fresh tumor biopsy on study unless determined medically unsafe or not feasible by the treating investigator. If a target lesion is biopsied at screening, this lesion must be followed as non-target lesion after the biopsy unless it is the patient's only target lesion.
• Participants must have normal organ and marrow function as defined below within 42 days prior to first study treatment
• A female participant is eligible to participate if they are not pregnant (negative urine or serum pregnancy test within 42 days prior to registration), not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) A WOCBP who agrees to follow tcontraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
• A male participant must agree to use contraception as of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.

You may not qualify if:

• Participants who have had prior systemic checkpoint inhibitors (anti-PD-1/L1 or anti-CTLA-4) and/or axitinib for the management of metastatic RCC.
• Participants who have had any type of anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy, small molecule kinase inhibitor or chemotherapy) within 2 weeks prior to enrollment on the study.
• Radiotherapy for RCC within 14 days of first study treatment with the exception of a single fraction of radiation administered for palliation of symptoms.
• Presence of any toxicities attributed to prior anti-cancer therapy that are not resolved to ≤ grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events CTCAE version v5.0) or baseline before administration of study drug38 with the exception of alopecia or grade 2 fatigue.
• Participants who are receiving systemic immunosuppressive medications within 2 weeks of first study dose, including but not limited to: prednisone, dexamethasone, cyclosporin, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor (TNF) agents
• Treatment with short term (\<7 days), or low-dose systemic immunosuppressant medications (≤ 10 mg prednisone/day equivalent) within 2 weeks of first study dose is permitted.
• Patients with adrenal insufficiency on physiologic replacement doses of steroids (≤ 10 mg prednisone equivalent) may be enrolled.
• The use of inhaled, topical, ocular or intra-articular corticosteroids and mineralocorticoids are allowed for other non-RCC co-morbidities.
• Any active or recent history (within 6 months of first study dose) of autoimmune disease or syndrome that requires systemic corticosteroids (\>10 mg daily prednisone equivalent) or immunosuppressive medications.
• Patients with low risk disorders, such as vitiligo, controlled type I diabetes mellitus, hypo- or hyperthyroid disease, or surgical adrenal insufficiency requiring hormone replacement therapy, are permitted to enroll. Discuss with PI any additional disorders not on this list that may qualify.
• Participants with known untreated or symptomatic metastases to the brain, spinal cord or leptomeninges. Patients may be eligible if stable intracranial disease for at least 4 weeks before first study treatment as documented by magnetic resonance imaging (MRI) or computerized tomography (CT) imaging and if no ongoing requirement for steroids.
• Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on screening ECG \> 480 msec.
• Bleeding or thrombotic disorders or patients at risk for severe hemorrhage. Gastrointestinal malabsorption, gastrointestinal anastomosis, fistula, or any other condition that might affect the absorption of axitinib.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or axitinib.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• University of Oklahoma: lead
• Merck Sharp & Dohme LLC: collaborator
• Pfizer: collaborator

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Axitinib; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Abhishek Tripathi, MD

  Stephenson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2022
• First Posted: March 2, 2022
• Study Start: June 1, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: August 2, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share