QUILT-2.001: ALT-803 in Patients With Advanced Pancreatic Cancer in Conjunction With Gemcitabine and Nab-Paclitaxel

Phase 1

Completed

• Conditions: Advanced Pancreatic Cancer
• Interventions: Biological: Gemcitabine; Biological: Nab-paclitaxel; Biological: ALT-803

• Registration Number: NCT02559674
• Lead Sponsor: Altor BioScience

Brief Summary

This is a Phase Ib/II, open-label, multi-center, competitive enrollment and dose escalation study of ALT-803 in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer in conjunction with gemcitabine and nab-paclitaxel.

Detailed Description

The purpose of this study is to evaluate the safety and tolerability of escalating doses, to identify the Maximum Tolerated Dose (MTD) and designate a dose level for Phase II study (RP2D) of ALT-803 administered in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer.

To access the anti-tumor activity of ALT-803 administered in combination with gemcitabine and nab-paclitaxel as measured by objective response rate, overall survival, progression-free survival, time to progression, and duration of response in patients with advanced pancreatic cancer.

To Characterize the pharmacokinetic, immunogenicity, and serum cytokine profile of ALT-803 in combination with gemcitabine and nab-paclitaxel in treated patients. To correlate circulating cell free DNA and circulating tumor DNA with clinical outcomes of the study in treated patients.

Study Timeline

• Study First Submitted: 2015-09-23
• Study First Submitted QC: 2015-09-23
• Study First Posted: 2015-09-24
• Study Start: 2016-07
• Primary Completion: 2018-02-21
• Study Completion: 2018-02-21
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-24
• Last Update Posted: 2020-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

• Histologically or cytologically confirmed diagnosis of pancreatic cancer.

  • For dose escalation phase (Phase Ib) distant metastatic disease or unresectable disease and not a candidate for down staging to resection.
  • For expansion phase (Phase II) distant metastatic disease only.

• For dose escalation phase (Phase Ib) 0 or 1 prior lines of chemotherapy for advanced pancreatic cancer. Prior gemcitabine is allowed, however prior nab-paclitaxel is not allowed.

• For expansion phase (Phase II) no prior therapy for pancreatic cancer is allowed except for adjuvant therapy as long as it was completed ≥ 6 months prior to study treatment start

• Have at least one untreated and progressing tumor lesion that can be accurately measured according to Response Evaluation Criteria in Solid Tumor

• Prior radiation is allowed if the index lesion(s) remains outside of the treatment field or has progressed since prior treatment. Radiation therapy must have been completed at least 4 weeks prior to the baseline scan

• Resolved acute effects of any prior therapy to baseline or Grade ≤1

• The Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2

• Life expectancy ≥12 weeks

• Glomerular Filtration Rate (GFR) > 40mL (milliliter)/min; Creatinine ≤ 1.5 x ULN (Upper limit of Normal)

• Platelets ≥100,000/uL (microliter)

• Hemoglobin ≥ 9g/dL

• Absolute Lymphocytes ≥800/uL

• Absolute neutrophil count/absolute granulocyte count ≥1500/uL

• Total bilirubin ≤ 2.0 X ULN, or ≤ 3.0 X ULN (for patients with Gilbert's Syndrome)

• aspartate aminotransferase, alanine aminotransferase ≤ 2.5 X ULN, or ≤ 5.0 X ULN (if liver metastasis present)

• Normal clinical assessment of pulmonary function

• Negative serum pregnancy test if female and of childbearing potential

• Subjects, both females and males, with reproductive potential must agree to use effective contraceptive measures for the duration of the study

• Must provide informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations

Exclusion Criteria

• No women who are pregnant or nursing
• No known hypersensitivity to gemcitabine or nab-paclitaxel
• No concurrent herbal or unconventional therapy
• No prior therapy with IL-15 or IL-15 analog
• No ongoing toxicity from prior anti-cancer treatment that may interfere with study treatment. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must resolve to grade 1 or baseline before administration of the study treatment.
• No positive Hep C serology or active Hep B infection
• No congestive heart failure < 6 months
• No unstable angina pectoris < 6 months
• No myocardial infarction < 6 months
• No history of ventricular arrhythmias or severe cardiac dysfunction
• No history of uncontrollable supraventricular arrhythmias
• No New York Heart Association Class > II congestive heart failure
• No marked baseline prolongation of QT/QTc interval
• No known autoimmune disease requiring active treatment. Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
• No known prior organ allograft or allogeneic transplantation
• No known HIV-positive or AIDS unless patient is on a stable highly active antiretroviral therapy (HAART) regimen, have CD4 (cluster of differentiation 4) counts >350, with no detectable viral load on quantitative polymerase chain reaction test
• No untreated central nervous system metastases, or if treated must be neurologically stable for at least 2 weeks prior to enrollment
• No corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent)
• No psychiatric illness/social situation that would limit compliance
• No other illness that in the opinion of the investigator would exclude the subject from participating in the study
• No active systemic infection requiring parenteral antibiotic therapy
• No anti-cancer treatment including surgery, radiotherapy, chemotherapy, other immunotherapy, or investigational therapy within 14 days before treatment start
• No disease requiring systemic immunosuppressive therapy
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 3 years after surgical treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Phase Ib/II ALT-803 w/ gemcitabine and nab-paclitaxel	Nab-paclitaxel	-
Phase Ib/II ALT-803 w/ gemcitabine and nab-paclitaxel	Gemcitabine	-
Phase Ib/II ALT-803 w/ gemcitabine and nab-paclitaxel	ALT-803	-

Primary Outcome Measures

Name	Time	Method
Determination of MTD; Phase Ib	9 Months	Determine the maximum tolerated dose (MTD) level and designate the recommended dose level for phase II.
Safety Profile (Number and severity of treatment related AEs); Phase Ib and II	48 Months	Number and severity of treatment related adverse events (AEs) that occur or worsen after the first dose of study treatment
Overall Survival; Phase II	8.5 Months	Determine the 8.5 month overall survival of treated patients

Secondary Outcome Measures

Name	Time	Method
Objective response rate	72 Months	Evaluate objective response rate in treated patients.
Duration of response	72 Months	Evaluate duration of response in treated patients.
Time to progression	72 Months	Evaluate time to progression in treated patients.
Progression-free survival	72 Months	Evaluate progression-free survival in treated patients.
Biomarkers; Phase Ib	36 Months	Measure the serum levels of the following including but not limited to Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6), Interleukin-10 (IL-10), Interferon-gamma (IFN-ɣ), Tumor necrosis factor-alpha (TNF-α) and Monocyte chemoattractant protein-1 (MCP-1)
Correlation between the level of circulating cell free DNA in patient plasma and response to study treatment	36 Months	Correlation between the level of circulating cell free DNA in patient plasma and response to study treatment
Correlation between the level of tumor DNA in patient plasma and response to study treatment	36 Months	Correlation between the level of tumor DNA in patient plasma and response to study treatment
Determine the level of anti-ALT-803 antibodies in patient serum	36 Months	Determine the level of anti-ALT-803 antibodies in patient serum
Area under the plasma concentration-time curve from time zero to infinity (AUC); Phase Ib	36 Months	Area under the plasma concentration-time curve from time zero to infinity (AUC)

Trial Locations

Locations (1)

University of Hawaii Cancer Center; 🇺🇸 Honolulu, Hawaii, United States