Trial Title:
A Study of Oral 7HP349 (Alintegimod) in Combination with Ipilimumab Followed by Nivolumab Monotherapy
NCT ID:
NCT06362369
Condition:
Advanced Cancer
Advanced Solid Tumor
Melanoma
Metastasis
Pleural Mesothelioma
Renal Cell Carcinoma
MSI-High
Mismatch Repair Deficiency
Colorectal Cancer
Hepatocellular Carcinoma
Hepatocellular Cancer
Renal Cell Cancer
Kidney Cancer
Skin Cancer
Non Small Cell Lung Cancer
NSCLC
Anaplastic Lymphoma Kinase Genomic Tumor Aberrations
ALK Genomic Tumor Aberrations
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Carcinoma, Renal Cell
Mesothelioma
Kidney Neoplasms
Liver Neoplasms
Nivolumab
Ipilimumab
Conditions: Keywords:
Phase 1
Phase 1b
7 Hills Pharma
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
Phase 1b - Open Label
Intervention:
Intervention type:
Drug
Intervention name:
Alintegimod
Description:
Alintegimod will be provided in bottles of 30 softgel capsules for oral administration
Arm group label:
Dose Escalation - Open Label Phase 1b
Other name:
7HP349
Intervention type:
Drug
Intervention name:
Ipilimumab
Description:
Ipilimumab (Yervoy) will be administered via IV
Arm group label:
Dose Escalation - Open Label Phase 1b
Other name:
Yervoy
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
Nivolumab (Opdivo) will be administered via IV
Arm group label:
Dose Escalation - Open Label Phase 1b
Other name:
Opdivo
Summary:
This study is an open-label Phase Ib (Part A) dose escalation followed by a blinded,
randomized, multi cohort Phase 2a (Part B) comparison of combination vs. reference
regimens.
Currently study will only be enrolling the Phase 1b and the Phase 2a protocol
requirements will be added to the study near completion of the Phase 1b
Detailed description:
This Phase study is designed to evaluate the safety, tolerability, and preliminary
efficacy of oral Alintegimod (Alintegimod) alone, and then in combination with ipilimumab
for, followed by nivolumab monotherapy cycles. All patients will receive nivolumab after
completion of treatment with Alintegimod plus ipilimumab combination therapy to continue
nivolumab treatment until the end of study (12 months) unless progression or toxicity
result in early termination.
Criteria for eligibility:
Criteria:
Inclusion and Exclusion Criteria for Phase 1b
Inclusion Criteria
1. Adult patients (age 18 or older)
2. Patient has a histologically confirmed diagnosis of any of the following locally
advanced or metastatic solid tumors: melanoma, pleural mesothelioma, renal cell
carcinoma, MSI-high or mismatch repair-deficient colorectal cancer, hepatocellular
carcinoma, and non-small cell lung cancer with no EGFR or anaplastic lymphoma kinase
(ALK) genomic tumor aberrations, or tumor types for which the combination of
ipilimumab and nivolumab has been FDA approved. Patients may have received treatment
with anti PD-1/PD-L1.
3. ANC > 1000/µL without use of G-CSF, Hgb > 9 g/dL without required blood
transfusion for at least 5 days prior to pretreatment baseline, and platelet count
> 75,000/µL without transfusions for at least 5 days prior to pretreatment
baseline.
4. ECOG performance status of 0 or 1.
5. Has a life expectancy of > 12 weeks.
6. Renal and hepatic function requirements:
- a. Renal function with either an eCrCL > 60 mL/min (modified
Cockcroft-Gault) or eGFR > 60 mL/min/1.73 m2 (using MDRD or CKD-EPI or
similar equations).
- b. Hepatic function with ALT/AST ≤ 3 x ULN, total bilirubin < 1.5 x ULN
(except for patients with Gilbert Syndrome). If patients have hepatic
metastases, then AST/ALT < 5 x ULN will be allowed.
7. Men receiving the investigational drug and are sexually active with women of
child-bearing potential (WCBP) must use contraception during treatment and for 5
half-lives after the last dose of the investigational drug or Women, not otherwise
meeting other exclusion criteria, who are WCBP must be on contraception for a
minimum duration of 3 months prior to treatment and continue contraception during
treatment and for 5 half-lives after the last dose of the investigational drug.
8. All Grade 3 AEs related to prior therapies have returned to Grade 1 or resolved to
baseline (this includes with appropriate therapy in the case of thyroid
dysfunction).
9. All patients must have measurable disease by applicable RECIST criteria.
10. Willing to allow blood samples to be used for research.
Exclusion Criteria:
1. Patients must not have received prior anticancer therapy or radiation therapy within
the 3 weeks and must not have undergone major surgery within 4 weeks prior to
initiation of treatment on protocol. Palliative radiation therapy is allowed. For
small molecules (MW < 0.9 kDA), the washout period is 3 weeks or 5 half-lives,
whatever comes first.
2. Active brain metastasis or leptomeningeal disease. Patients with treated brain
metastasis must have stable disease, evidenced by MRI brain imaging for at least 4
weeks, and the patient must have been off steroids for at least 2 weeks prior to
first dose of study drug.
3. Previous episodes of ≥ Grade 3 (G3) immune-related toxicity that includes G3
colitis, G3 pneumonitis, G3 skin rash, G3 increase in liver enzymes (with the
exception of symptoms that in the opinion of the investigator will not compromise
the patients' safety on the trial. Patients with stable endocrinological AEs (e.g.,
hypothyroidism, adrenal insufficiency, hypopituitarism, or diabetes mellitus) are
allowed.
4. Persistent toxicity of NCI CTCAE version 5 Grade > 1 severity that is related to
prior therapy.
Note: Sensory neuropathy, hypothyroidism or alopecia of Grade ≤ 2 are acceptable.
Other Grade 2 toxicities of prior treatments that are controlled with medication
(e.g., diabetes or hypertension) are permitted.
5. Concurrent administration of medications or foods that are strong inhibitors or
inducers of cytochrome p450 3A (CYP3A) within 2 weeks before study intervention.
Alintegimod may increase exposure to CYP3A4 substrates; consider a dose reduction of
such substrates and monitor for signs of toxicities of co-administered sensitive
CYP3A substrates (see listing of strong inhibitors and inducer drugs in FDA tables).
An alternative is to replace such agents with drugs that are not CYP3A4 metabolized
if at all feasible.
6. The patient has cardiac conditions as follows:
- a) myocarditis;
- b) uncontrolled hypertension (blood pressure > 160/100) despite optimal
therapy;
- c) uncontrolled angina; ventricular arrhythmias; congestive heart failure (New
York Heart Association Class II or above);
- d) prior or current cardiomyopathy;
- e) uncontrolled atrial fibrillation with heart rate > 100 beats per minute
(bpm); unstable ischemic heart disease (myocardial infarction within 6 months
prior to starting treatment or angina requiring use of nitrates more than once
weekly);
- f) concomitant medication with drugs known to cause Torsades de Pointes;87
- g) QT interval correction for heart rate using Fridericia's formula (QTcF) ≥
470 ms (average from 3 QTcF values on the triplicate 12-lead electrocardiogram
[ECG]) at screening.
7. Known history of a positive test for HIV, or positive test for hepatitis B (positive
for HBsAg) or hepatitis C (HCV RNA).
8. Concurrent malignancies are permitted if they were previously treated, and all
treatment of that malignancy was completed at least 2 years before enrollment and no
evidence of disease exists, or with agreement from the Principal Investigator (PI),
patients who have a concurrent malignancy that is clinically stable and does not
require tumor-directed treatment are eligible to participate if the risk of the
prior malignancy interfering with either safety or efficacy endpoints is very low,
or with agreement from the PI, other malignancies may be permitted if the risk of
the prior malignancy interfering with either safety or efficacy end points is very
low. Adequately treated basal or squamous cell carcinoma or carcinoma in situ is
allowed.
9. Men receiving the investigational drug and are sexually active with women of
child-bearing potential (WOCBP) must use contraception during treatment and for 5
half-lives after the last dose of the investigational drug or Women, not otherwise
meeting other exclusion criteria, who are WOCBP must be on contraception for a
minimum duration of 3 months prior to treatment and continue contraception during
treatment and for 5 half-lives after the last dose of the investigational drug.
10. The patient has concurrent severe and/or uncontrolled medical disease that could
compromise participation in the study (i.e., uncontrolled diabetes, severe infection
requiring active treatment, severe malnutrition, chronic severe liver or renal
disease).
11. Use of corticosteroids or other immunosuppressive medication, current or within 14
days of administration of Alintegimod with the following exceptions:
- a) Topical, intranasal, inhaled, ocular, intra-articular corticosteroids;
- b) Physiological doses of replacement corticosteroids (e.g., for adrenal
insufficiency) are not to exceed 10 mg/day of prednisone or equivalent.
12. Corticosteroid premedication for infusion and/or hypersensitivity reactions.
13. Receipt of live attenuated vaccine within 28 days of the first dose of Alintegimod.
14. Serious autoimmune disease at the discretion of the treating Investigator: patients
with a history of active serious inflammatory bowel disease (including Crohn's
disease and ulcerative colitis) and autoimmune disorders such as rheumatoid
arthritis, systemic progressive sclerosis (scleroderma), systemic lupus
erythematosus or autoimmune vasculitis (e.g., Wegener's Granulomatosis) are
excluded from participation in this study
15. Active or history of pneumonitis (drug-induced), idiopathic pulmonary fibrosis,
Interstitial Lung Disease (ILD), or lung disease that may interfere with assessment
of pneumonitis. History of radiation pneumonitis in a previous radiation field is
permitted.
16. Previous participation in a study of any investigational agent within 21 days of
enrollment or within 5 half-lives of the study treatment, whichever is the least.
17. Use of mechanical ventilation or having a resting O2 saturation < 90% (on room
air) by pulse-oximetry, require renal dialysis, require vasopressors, and/or severe
hepatic sinusoidal obstruction syndrome.
18. Proven or suspected ongoing systemic infection requiring IV antibiotics.
19. Women who are pregnant or lactating.
Note: Women of childbearing potential (WOCBP) must have a "negative" serum pregnancy
test within 1 week prior to treatment. Non-childbearing potential is defined as 1 of
the following:
- i. Postmenopausal with > 1 year since last menses and:
-
1. If < 65 years old, follicle-stimulating hormone (FSH) > 40 mIU/mL.
-
2. If ≥ 65 years old and not on hormone replacement therapy (HRT), FSH >
30 mIU/mL.
-
3. If ≥ 65 years old and on HRT, the FSH requirement is not applicable.
Postmenopausal females on HRT will be allowed if HRT has been stable for ≥
6 months prior to dosing of study drug(s).
- ii. Written medical documentation of being sterilized (e.g., hysterectomy,
double oophorectomy, bilateral salpingectomy) with the procedure performed ≥ 6
months prior to dosing study drug(s).
Note: Tubal ligation is not considered a form of permanent sterilization.
20. Psychiatric illness/social circumstances that would limit compliance with study
requirements and substantially increase the risk of adverse events or have
compromised ability to provide written informed consent.
21. Patients who have had allogeneic tissue or solid organ transplantation. Prior T cell
therapy is allowed
22. Use of biotin (i.e., Vitamin B7) or supplements containing biotin higher than the
daily adequate intake of 30 µg (NIH-ODS 2022; Section 5.9.2.1).88 Note: Patients who
switch from a high dose to a dose of ≤30 µg/day are eligible for study entry.
23. Any condition that is in the opinion of the investigator may compromise patient's
participation in the trial.
24. Active peptic ulcer disease or gastritis, active diverticulitis, or other serious
gastrointestinal disease associated with diarrhea within the past 2 years before the
start of therapy or GI disease which affects oral drug absorption.
25. Patients with known soy allergy.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Florida Cancer Specialists
Address:
City:
Lake Mary
Zip:
32746
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
(407) 804-6133
Email:
ClinicalTrials@FLCancer.com
Contact backup:
Last name:
Alexander Philipovskiy, MD, PhD
Facility:
Name:
Dartmouth Hitchcock
Address:
City:
Lebanon
Zip:
03756
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Study Coordinator
Phone:
603.650.6345
Contact backup:
Last name:
Konstantin H Dragnev, MD
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
713.792.4259
Contact backup:
Last name:
Apostolia-Maria Tsimberidou, MD, PhD
Start date:
August 23, 2024
Completion date:
December 31, 2028
Lead sponsor:
Agency:
7 Hills Pharma, LLC
Agency class:
Industry
Source:
7 Hills Pharma, LLC
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06362369
