A study on NKTR-255 in combination with Cetuximab as salvage treatment for Solid Tumors

Phase 1

• Conditions: Relapsed or refractory (R/R) head and neck squamous cell carcinoma (HNSCC) or colorectal carcinoma (CRC); MedDRA version: 20.0Level: LLTClassification code 10007336Term: Carcinoma colon recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10009963Term: Colon carcinoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 22.0Level: LLTClassification code 10082179Term: Squamous cell carcinoma of head and neck metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-002177-25-ES
• Lead Sponsor: ektar Therapeutics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-07-20
• Last Update Posted: 6 December 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

Inclusion Criteria for All Patients
1. Patients must be at least 18 years of age at study entry
2. Patients must be capable of understanding and providing a written informed consent.
3. Women of childbearing potential (WCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) at Screening and a negative serum or urine pregnancy test within 24 hours prior to dosing. Women of childbearing potential and men who are sexually active with women of childbearing potential must commit to use contraception.
4. Histologically confirmed diagnosis of a locally advanced (not amenable to curative therapy such as surgical resection) or metastatic cancer of the following histologies: HNSCC or CRC
5. Patients who have previously received cetuximab or other EGFR-directed therapies are excluded from Phase 2 of the trial, unless cetuximab was given as part of a primary treatment approach, with no progressive disease for at least 4 months following the end of prior cetuximab treatment.
6. Life expectancy > 12 weeks as determined by the Investigator
7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
8. Measurable disease per RECIST 1.1
9. Patients must have demonstrated adequate organ function during Screening:
a. Estimated glomerular filtration rate = 40 mL/min/1.73m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation
Inclusion Criteria for Specific Tumor Types
• Head and Neck Cancer
1. Patients must have histologically or cytologically confirmed advanced, recurrent, or metastatic HNSCC that could not be treated with curative intent. Advanced” is defined as either locally advanced HNSCC not amenable to curative surgery or radiotherapy or with distant metastases.
2. Progression (or toxicity precluding additional treatment) on any first or second line platinum-based chemotherapy and/or anti-PD-1 or programmed death-ligand 1 (anti-PD-L1) (together termed anti-PD-(L)1) antibody
3. Patients who have undergone treatment with anti-PD-(L)1 antibody must have had the last dose of antibody at least 4 weeks prior and evidence of tumor progression before they can be enrolled into this study.
4. Ineligible for platinum-based (either cisplatin or carboplatin) chemotherapy or chemoradiation due to decline in renal function and/or patient's intolerance
5. Must have known status by pathology for human papillomavirus (HPV) and Epstein-Barr virus (EBV) in HNSCC, either metastatic or recurrent disease.
• Colorectal Cancer
1. Patients must have a histologically or cytologically confirmed diagnosis of advanced CRC; patients in Phase 2 must have confirmed KRAS wild type EGFR-expressing advanced CRC. Advanced” is defined as either locally advanced unresectable cancer or metastatic disease.
2. Patients must have received or were intolerant to at least 2 prior cancer therapy regimens administered for metastatic disease.
3. Patients with high microsatellite instability (MSI-H) or mismatched repair disease (dMMR) tumors must have been exposed to checkpoint inhibitors such as anti-PD-(L)1 or anticytotoxic T-lymphocyte-associated protein (CTLA)-4 antibody.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 51
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 27

Exclusion Criteria

1.Use of an IMP or an investigational device within 28 days before administration of first dose of study drug(s)
2.Active, known, or suspected autoimmune disease. Patients requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease that requires systemic corticosteroids or immunosuppressive.
3.History of allergy or known hypersensitivity to murine protein or study drug components
4.History of organ transplant that requires ongoing use of immunosuppressive agents
5.Patients who have been previously treated with IL-2 or IL-15
6.Patients with HNSCC who require treatment with anticoagulation therapy are not eligible.
7.Contraindication to or unable to receive cetuximab
8.Patient has had prior Grade 4 IRR to cetuximab
9.Unresolved toxicity from previous anti-cancer therapy, unless resolved to Grade = 1; or resolved to Grade 2; or resulting from incomplete recovery from surgery
10.Prior surgery or radiotherapy within 14 days of initiating study drug(s). Patients must have recovered from all radiation-related toxicities.
11.Patients participating in observational studies should be discussed with the Medical Monitor to confirm eligibility.
12.Patients who have had < 28 days since the last anti-cancer treatment, chemotherapy or biological therapy, or < 14 days from approved tyrosine kinase inhibitor therapy, or systemic or inhaled steroid therapy at doses greater than 10 mg of prednisone or equivalent before administration of the first dose of study drug(s).
13.Patients who have received systemic interferon alpha within the previous 6 months prior to enrollment in the study are not eligible.
14.Active infection requiring systemic therapy within 7 days prior to dosing
15.Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis
16.Known immunodeficiency or active human immunodeficiency virus (HIV)
17.Known to be seropositive or active for hepatitis B or hepatitis C
18.QTcF> 450 ms for men and > 470 ms for women at Screening
19. History of unstable or deteriorating cardiac disease within the previous 6 months prior to Screening
20.Has a known additional malignancy that is progressing or requires active treatment, exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
21.Patient has any of the following laboratory test results during Screening:
a.AST and ALT level = 2.5 times ULN;
b.Alkaline phosphatase level = 2.5 × ULN;
c.Total bilirubin level = 2 × ULN;
d.Potassium level < 3.0 mEq/L; or
e.Corrected serum calcium > 14.0 mg/dL (3.5 mmol/L)
22.Patient is a woman who is pregnant or breastfeeding or planning to become pregnant while enrolled in this study or within 4 weeks after the last dose of NKTR-255 or within 2 months after the last dose of cetuximab.
23.Active brain metastases or leptomeningeal metastases patients with brain metastases are eligible if these have been treated and there is no radiographic evidence of progression for at least 4 weeks after treatment is complete. There must also be no requirement for immunosuppressive doses of systemic corticosteroids for at least 4 weeks prior to study treatment. Stable dose of anticonvulsants is required within 14 days prior to study treatment. Treatment for central nervous system metastases may include stereotactic radiosurgery or neurosurgical resection. Patients who received whole brain

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified