QUILT-3.055: A Study of ALT-803 in Combination With PD-1/PD-L1 Checkpoint Inhibitor in Patients With Advanced Cancer

INTRODUCTION

Org Study ID: CA-ALT-803-02-17
Secondary ID: N/A
NTC ID: NCT03228667
Sponsor: Altor BioScience

This is a Phase IIb, single-arm, multicohort, open-label multicenter study of ALT-803 in
combination with an FDA-approved PD-1/PD-L1 checkpoint inhibitor in patients with advanced
cancers who have progressed following an initial response to treatment with PD-1/PD-L1
checkpoint inhibitor therapy. All patients will receive the combination treatment of
PD-1/PD-L1 checkpoint inhibitor plus ALT-803 for up to 16 cycles. Each cycle is six weeks in
duration. All patients will receive ALT-803 once every 3 weeks. Patients will also receive
the same checkpoint inhibitor that they received during their previous therapy. Radiologic
evaluation will occur at the end of each treatment cycle. Treatment will continue for up to 2
years, or until the patient experiences confirmed progressive disease or unacceptable
toxicity, withdraws consent, or if the Investigator feels it is no longer in the patient's
best interest to continue treatment. Patients will be followed for disease progression,
post-therapies, and survival through 24 months past administration of the first dose of study
drug.

Overall Status
Recruiting
Start Date
December 11, 2018
Phase
Phase 2
Study Type
Interventional

Primary Outcome 1 - Measure: Objective Response Rate

Primary Outcome 1 - Timeframe: 24 months

Non-Small Cell Lung Cancer
Small Cell Lung Cancer
Urothelial Carcinoma
Head and Neck Squamous Cell Carcinoma
Merkel Cell Carcinoma
Melanoma
Renal Cell Carcinoma
Gastric Cancer
Cervical Cancer
Hepatocellular Carcinoma
Microsatellite Instability
Mismatch Repair Deficiency
Colorectal Cancer

Inclusion Criteria:

• Voluntary written informed consent and HIPAA authorization and agree to comply with all
protocol-specified procedures and follow-up evaluations

1. Cohort 1 will enroll patients who have disease progression per RECIST v1.1 on or after
single-agent checkpoint inhibitor therapy after experiencing an initial response (ie,
confirmed CR or PR by RECIST V1.1) while taking checkpoint inhibitor therapy. Patients
will be enrolled into distinct cohorts (1a-1k) based on cancer type.

Patients must have been treated with checkpoint inhibitor therapy after progressing on
SoC therapy for their disease, as per FDA indication detailed below:

- 1a - For metastatic squamous or nonsquamous NSCLC with progression on or after
nivolumab, pembrolizumab, or atezolizumab, initial SoC therapy must have been for
disease with progression on or after one prior platinum doublet-based
chemotherapy regimen. Patients with EGFR or ALK genomic tumor aberrations should
have had disease progression on FDA-approved targeted therapy for these
aberrations prior to receiving checkpoint inhibitor.

- 1b - For metastatic SCLC with disease progression on or after nivolumab
monotherapy, initial SoC treatment must have been for disease with progression
after platinum-based chemotherapy and at least one other line of therapy prior to
receiving checkpoint.

- 1c - Locally advanced or metastatic urothelial carcinoma as follows:

- For patients with progression on or after nivolumab monotherapy, initial SoC must
have been for disease with progression on or after platinum-based chemotherapy or
within 12 months of neoadjuvant or adjuvant treatment with platinum-based
chemotherapy.

- For patients with disease progression on or after pembrolizumab, initial SoC
therapy may have been for locally advanced or metastatic urothelial carcinoma
ineligible for cisplatin-containing chemotherapy with PD-L1 tumor expression of
CPS ≥ 10 (as determined by FDA-approved test), OR metastatic urothelial carcinoma
not eligible for any platinum-containing chemotherapy regardless of PD-L1 status,
OR locally advanced or metastatic urothelial carcinoma with progression on or
after platinum-based chemotherapy or within 12 months of neoadjuvant or adjuvant
treatment with platinum-based chemotherapy.

- For patients with disease progression on or after atezolizumab, initial SoC
therapy may have been for locally advanced or metastatic urothelial carcinoma not
eligible for cisplatin-based chemotherapy that expresses PD-L1 (PD-L1 stained
tumor-infiltrating immune cells [IC] covering ≥ 5% of the tumor area, as
determined by an FDA-approved test), OR not eligible for cisplatin-based
chemotherapy regardless of PD-L1 status, OR with progression on or after
platinum-based chemotherapy or within 12 months of neoadjuvant or adjuvant
treatment with platinum-based chemotherapy.

- For patients with disease progression on or after avelumab, initial SoC therapy
may have been for locally advanced or metastatic urothelial carcinoma with
progression on or after platinum-based chemotherapy or within 12 months of
neoadjuvant or adjuvant treatment with platinum-based chemotherapy.

- 1d - Recurrent or metastatic HNSCC as follows:

- For patients with disease progression on or after nivolumab monotherapy, initial
SoC treatment must have been for disease with progression on or within 6 months
of a platinum-based therapy administered in the adjuvant, neoadjuvant, primary
(unresectable locally advanced), or metastatic setting.

- For patients with disease progression on or after pembrolizumab monotherapy,
initial SoC treatment must have been for disease with progression on or after
platinum-based chemotherapy, or after platinum-based chemotherapy administered as
part of induction, concurrent, or adjuvant therapy.

- 1e - For histologically confirmed metastatic MCC with progression on or after
avelumab or pembrolizumab, initial SoC therapy must have been for disease with
progression on or after chemotherapy administered for distant metastatic disease;
OR recurrent locally advanced or metastatic MCC not treated with prior systemic
therapy for advanced disease.

- 1f - Metastatic melanoma as follows:

- For patients with disease progression on or after nivolumab administered as a
single agent, in combination with ipilimumab, or in the adjuvant setting, initial
SoC treatment must have been for unresectable or metastatic melanoma with
progression on or after ipilimumab treatment, and if BRAF V600 mutation positive,
a BRAF inhibitor; OR BRAF V600 wild-type unresectable or metastatic melanoma
previously untreated in the metastatic setting; OR previously untreated,
unresectable, or metastatic melanoma not previously treated with anti-CTLA4
antibody; OR completely resected melanoma with lymph node involvement, or stage
IIIB/C or stage IV metastatic disease.

- For patients with disease progression on or after pembrolizumab therapy, initial
SoC treatment must have been for unresectable or metastatic melanoma with no
prior ipilimumab, and no more than 1 prior systemic treatment for metastatic
disease. Patients with BRAF V600E mutation-positive melanoma were not required to
have received prior BRAF inhibitor therapy; OR unresectable or metastatic
melanoma with progression, refractory to ≥ 2 doses of ipilimumab (3 mg/kg or
higher) and, if BRAF V600 mutation-positive, a BRAF or MEK inhibitor, and disease
progression within 24 weeks following the last dose of ipilimumab.

- 1g - For advanced RCC with progression on or after nivolumab monotherapy, initial
SoC therapy must have been for disease that progressed after 1 or 2 prior
anti-angiogenic therapy regimens. For intermediate or poor risk previously
untreated advanced RCC, patients must have progressed on or after nivolumab +
ipilimumab.

- 1h - For recurrent locally advanced or metastatic gastric or gastroesophageal
junction adenocarcinoma with progression on or after pembrolizumab, initial SoC
therapy must have been for disease that progressed on or after ≥ 2 prior lines of
therapy including fluoropyrimidine- and platinum-containing chemotherapy and, if
appropriate, HER2/neu-targeted therapy. Tumors must express PD-L1 (combined
positive score [CPS] ≥ 1), as determined by an FDA-approved test.

- 1i - For recurrent or metastatic cervical cancer with progression on or after
pembrolizumab, initial SoC therapy must have been for disease that progressed on
or after chemotherapy. Tumors must express PD-L1 (CPS ≥ 1), as determined by an
FDA-approved test.

- 1j - For HCC with progression on or after pembrolizumab, initial SoC treatment
must have been for disease that progressed on or after sorafenib or intolerant to
sorafenib. Patients must have had measureable disease and Child-Pugh class A
liver impairment. For HCC with progression on or after nivolumab, initial SoC
treatment must have been for histologically confirmed HCC with progression on
sorafenib or intolerant to sorafenib, and Child-Pugh class A.

- 1k -Unresectable or metastatic MSI-H or dMMR solid tumors as follows:

- For patients with progression on or after nivolumab administered as a single
agent or in combination with ipilimumab, initial SoC therapy must have been for
MSI-H or dMMR metastatic CRC with progression on or after treatment with a
fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

- For patients with progression on or after pembrolizumab, initial SoC therapy must
have been for unresectable or metastatic MSI-H or dMMR solid tumors with
progression after prior treatment and no satisfactory alternative treatment
options; OR unresectable or metastatic MSI-H or dMMR CRC with progression after
treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

2. For cohort 2, patients with NSCLC whose tumors have high PD-L1 expression (TPS ≥ 50%)
and who have disease progression by RECIST v1.1 on a PD-1 checkpoint inhibitor after
experiencing an initial confirmed CR or PR by RECIST v1.1 when they received
checkpoint inhibitor as a single-agent for first-line treatment.

3. For cohort 3, patients with NSCLC who had an initial confirmed CR or PR by RECIST v1.1
but subsequently relapsed (ie, disease progression by RECIST v1.1) on maintenance PD-1
checkpoint inhibitor therapy when they initially received checkpoint inhibitor therapy
in combination with chemotherapy as first-line treatment.

4. For cohort 4, patients with NSCLC, HNSCC, RCC, or urothelial carcinoma who are
currently receiving PD-1/PD-L1 checkpoint inhibitor therapy and have disease
progression after experiencing SD by RECIST v1.1 for at least 6 months during their
previous treatment with PD-1/PD-L1 checkpoint inhibitor therapy.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Measurable disease by CT or MRI, as defined by RECIST v1.1

- Treatment of at least 3 months and 1 imaging assessment indicative of a confirmed
CR or PR (in accordance with RECIST V1.1) with checkpoint inhibitor (no more than
6 weeks of treatment interruption immediately prior to study enrollment).

- Patients with genomic tumor aberrations should have received prior treatment with
an FDA-approved targeted therapy (if available)

- Current progressive disease, as defined by RECIST v1.1

- Adequate organ system function within 14 days of baseline:

- ANC ≥ 750/µL (≥0.75 x 10^9/L)

- Platelets ≥ 100,000/µL (≥100 x 10^9/L)

- Hemoglobin > 8 g/dL

- Total bilirubin < 2.0 x ULN

- AST < 3.0 x ULN

- ALT < 3.0 x ULN

- eGFR > 45 mL/min

- Men and women, ≥ 18 years of age

- Female participants / women of childbearing potential (WOCBP) must adhere to
using a medically accepted method of birth control up to 28 days prior to
screening and agree to continue its use during the study or be surgically
sterilized (e.g., hysterectomy or tubal ligation) and males must agree to use
barrier methods of birth control while on study. WOCBP must agree to use
effective contraception during treatment and for at least 5 months following the
last dose of study treatment.

- Women of child-bearing potential must have a negative serum pregnancy test during
Screening and a negative urine pregnancy test within 24 hours prior to first dose
of study treatment. Non-childbearing is defined as greater than one year
postmenopausal or surgically sterilized.

Exclusion Criteria:

- Patients with CNS metastases with the following exceptions:

- Patient untreated CNS metastases with 4 or fewer sites of disease, with no single site
larger than 20mm, are eligible if they are asymptomatic and not requiring steroids at
any dose. Patients with asymptomatic CNS metastases may be treated with radiosurgery
before or during therapy on trial without treatment delays.

- Patients with treated, symptomatic CNS metastases are eligible if they are
neurologically returned to baseline (except for residual signs or symptoms related to
the CNS treatment) for at least 2 weeks prior to registration AND either off
corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or
equivalent).

- New York Heart Association (NYHA) Class III or IV heart failure, uncontrollable
supraventricular arrhythmias, any history of a ventricular arrhythmia, or other
clinical signs of severe cardiac dysfunction

- Symptomatic congestive heart failure, unstable angina pectoris, or myocardial
infarction within 6 months of enrollment

- Known autoimmune disease requiring active treatment.

- History of interstitial lung disease and/or immune mediated pneumonitis

- Known HIV-positive

- Active systemic infection requiring parenteral antibiotic therapy

- Positive hepatitis C serology or active hepatitis B infection

- Any ongoing toxicity from prior anti-cancer treatment that, in the judgement of the
investigator, may interfere with study treatment. All toxicities attributed to prior
anti-cancer therapy other than alopecia and fatigue must resolve to grade 1 (NCI CTCAE
version 4) or baseline prior to enrollment. Eligible patients must not require more
than 10 mg/day prednisone (or equivalent dose).

- Previous malignancies (except non-melanoma skin cancers, in situ bladder cancer, in
situ gastric or in situ colon cancers, in situ cervical cancers/dysplasia or breast
carcinoma in situ) unless a complete remission was achieved at least 1 year prior to
study entry and no additional therapy is required or anticipated to be required during
the study period

- No other illness that in the opinion of the investigator would exclude the subject
from participating in the study

- Patients in which treatment with PD-1/PD-L1 checkpoint inhibitor is contraindicated

- Patients who have received another investigational agent within the previous 3 months

- Women who are pregnant or nursing

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

Name: N/A

Role: N/A

Affiliation: N/A

Name: N/A

Phone: 954-443-8600

Email: Amy.Rock@ImmunityBio.com

Facility	Status	Contact
Facility: Alaska Clinical Research Center Anchorage, Alaska 99530 United States	Status: Recruiting	Contact: Ashli Meek 907-276-1455 ameek@akmed.com
Facility: Chan Soon-Shiong Institute for Medicine El Segundo, California 90245 United States	Status: Recruiting	Contact: Clinical Trials Navigator patients@cssifm.org
Facility: Glendale Adventist Medical Center Glendale, California 91206 United States	Status: Recruiting	Contact: Javier Valeriano 818-409-8009 javier.valeriano@ah.org
Facility: Desert Hematology Oncology Medical Group, Inc. Rancho Mirage, California 92270 United States	Status: Recruiting	Contact: Carolyn Arrieta carolyndho@aol.com
Facility: Memorial Healcare System Hollywood, Florida 33021 United States	Status: Recruiting	Contact: Jayme Ion 954-265-1847 jion@mhs.net
Facility: University of Miami Miami, Florida 33180 United States	Status: Recruiting	Contact: Maria Pardo m.pardo3@umiami.edu
Facility: Baptist Health - Lexington Lexington, Kentucky 40503 United States	Status: Recruiting	Contact: Karli Heasley karli.heasley@BHSI.COM
Facility: Baptist Health- Louisville Louisville, Kentucky 40207 United States	Status: Recruiting	Contact: Renee Dickerson 502-897-1166 renee.dickerson1@BHSI.COM
Facility: Dana Farber Cancer Institute Boston, Massachusetts 02215 United States	Status: Recruiting	Contact: Brenda Paulino 617-632-4764 brenda_paulino@dfci.harvard.edu
Facility: Henry Ford Hospital Detroit, Michigan 48202 United States	Status: Recruiting	Contact: Trevor I Seixas 313-916-0482 tseixas1@hfhs.org
Facility: University of Minnesota - Masonic Cancer Center Minneapolis, Minnesota 55455 United States	Status: Recruiting	Contact: Nicole Sando 612-624-5949 daue0006@umn.edu
Facility: Mercy Research Joplin Joplin, Missouri 64804 United States	Status: Recruiting	Contact: Esmeralda R Carrillo Esmeralda.Carrillo@mercy.net
Facility: Washington University School of Medicine Saint Louis, Missouri 63110 United States	Status: Recruiting	Contact: Joe Murphy 314-273-2686 murphy.joe.p@wustl.edu
Facility: Mercy Clinic Cancer & Hematology - Chub O'Reilly Cancer Center Springfield, Missouri 65804 United States	Status: Recruiting	Contact: Jennifer Kahrs Jennifer.Kahrs@Mercy.Net
Facility: St. Vincent Frontier Cancer Center (SCL) Billings, Montana 59102 United States	Status: Recruiting	Contact: Sabrina Leonhardt 406-238-6290 sabrina.leonhardt@sclhealth.org
Facility: Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire 03756 United States	Status: Recruiting	Contact: Kristina M Willey 603-650-7705 tanya.m.perry@Kristina.M.Willey@hitchcock.org.org
Facility: Roswell Park Cancer Institute Buffalo, New York 14263 United States	Status: Recruiting	Contact: Rushka Kallicharan-Smith 716-845-1300 Rushka.Kallicharan-Smith@RoswellPark.org
Facility: University of Rochester Rochester, New York 14642 United States	Status: Recruiting	Contact: Amy Jasek Amy_Jasek@URMC.Rochester.edu
Facility: Cleveland Clinic - Main Site Cleveland, Ohio 44195 United States	Status: Recruiting	Contact: Makenzie Guy 216-445-8492 guym@ccf.org
Facility: Mercy Clinic Oklahoma City Oklahoma City, Oklahoma 73120 United States	Status: Recruiting	Contact: Sheryl R Freeland 405-752-3402 sheryl.freeland@mercy.net
Facility: Providence Portland Medical Center Portland, Oregon 97213 United States	Status: Recruiting	Contact: Kim Sutcliffe, RN 503-215-5696 KIMBERLY.SUTCLIFFE@providence.org
Facility: Medical University of South Carolina Charleston, South Carolina 29425 United States	Status: Recruiting	Contact: Alexandra Leitner 843-792-1507 leitnera@musc.edu
Facility: St. Francis Cancer Center/Bon Secours St. Francis Health System Greenville, South Carolina 29607 United States	Status: Recruiting	Contact: Gina Smith GINA_SMITH@bshsi.org
Facility: Spartanburg Medical Center Spartanburg, South Carolina 29303 United States	Status: Recruiting	Contact: Susan Stanley sstanley@gibbscc.org
Facility: Sanford Clinical Research Sioux Falls, South Dakota 57104 United States	Status: Recruiting	Contact: Jane Veerman, RN 605-328-1373 Jane.veerman@sanfordhealth.org
Facility: University of Tennessee Medical Center Knoxville, Tennessee 37920 United States	Status: Recruiting	Contact: Brenna Adelman 865-305-5131 BAdelman@utmck.edu
Facility: Bon Secours Richmond Richmond, Virginia 23114 United States	Status: Recruiting	Contact: Melissa S Godsey 804-893-8611 melissa_godsey@bshsi.org

Brief Title: QUILT-3.055: A Study of ALT-803 in Combination With PD-1/PD-L1 Checkpoint Inhibitor in Patients With Advanced Cancer

QUILT-3.055: A Phase IIb, Single-Arm, Multicohort, Open-Label Study of ALT-803 in Combination With PD-1/PD-L1 Checkpoint Inhibitor in Patients Who Have Disease Progression Following an Initial Response to Treatment With PD-1/PD-L1 Checkpoint Inhibitor Therapy

INTRODUCTION

BRIEF SUMMARY

PRIMARY OUTCOMES

CONDITION

ELIGIBILITY

OFFICIAL INFORMATION

Overall Contact

LOCATION

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