A randomized, run-in, phase II study of nivolumab combined with ipilimumab and guadecitabine or nivolumab combined with ipilimumab in melanoma and NSCLC patients resistant to anti-PD-1/PD-L1

Phase 1

• Conditions: MM and NSCLC patients resistant to anti-PD-1/PD-L1 therapy; MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-002986-36-IT
• Lead Sponsor: FONDAZIONE NIBIT NETWORK ITALIANO PER LA BIOTERAPIA DEI TUMORI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-03
• Last Update Posted: 17 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 184

Inclusion Criteria

Signed Written Informed Consent
Willing and able to give written informed consent.
Target Population Subjects must fulfill all of the following inclusion criteria:
Men and women of and over 18 years old
1) Target Population Melanoma cohort A
a) Histologic diagnosis of malignant melanoma
b) Unresectable Stage III/Stage IV melanoma patients with resistance to anti-PD-1/PD-L1 and measurable lesions
by CT or MRI per iRECIST/RECIST criteria that can be amenable to biopsy
c) Only one line of immunotherapy for advanced (unresectable Stage III or Stage IV) disease with anti-PD-1/PDL1
and its combinations; if BRAF mutant one line of targeted therapy is allowed prior to anti-PD-1/PDL1therapy.
2) Target Population NSCLC cohort B
a) Histologic or cytologic diagnosis of NSCLC lacking EGFR-sensitizing mutation and/or ALK/ROS1
translocation.
b) Stage IV NSCLC patients with primary resistance to anti-PD-1/PD-L1 and measurable lesions by CT or MRI
per iRECIST/RECIST criteria that can be amenable to biopsy.
c) Only one line of immunotherapy for advanced (unresectable Stage III or Stage IV) disease with anti-PD-1/PDL1
or its combinations; one line of chemotherapy is allowed prior to anti-PD-1/PDL-1 therapy.
3) confirmed PD
4) 4 weeks or greater since last treatment and
5) Must have recovered from any acute toxicity associated with prior therapy
6) Life expectancy greater than 16 weeks
7) Subjects with adequate organ function defined as:
a) WBC =3500/uL
b) ANC =2000/uL
c) Platelets = 100 x 103/uL
d) Hemoglobin = 9 g/dL
e) Creatinine < or <= 2.5 x ULN AND creatinine clearance (CrCl) = 40 mL/min (if using the Cockcroft-Gault formula below):
Female CrCl = (140 - age in years) x weight in kg x 0.85
72 x serum creatinine in mg/dL
Male CrCl = (140 - age in years) x weight in kg x 1.00
72 x serum creatinine in mg/dL
f) AST
- < or <= 2.5 x ULN for patients without liver metastasis
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- < or <= 5 x ULN for patients with liver metastasis
g) Bilirubin
- < or <= 3 x ULN for patients with liver metastasis
- <3.0 mg/mL for patients with Gilbert’s Syndrome
- 1.5 x ULN for patients without liver metastasis
8) Negative screening tests for HIV, HepB, and HepC. If positive results are not indicative of true active or chronic
infection, the patient can enter the study after discussion and agreement between the Investigator and the Medical Monitor.
9) Women of child-bearing potential must not be pregnant or breastfeeding, must have a negative pregnancy test at
Screening and all men must be practicing two medically acceptable methods of birth control. Men should not father a
child while receiving treatment with guadecitabine+ ipilimumab, and for 2 months following completion of treatment.
Men with female partners of childbearing potential should use effective contraception during this time.
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 184
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 184

Exclusion Criteria

1) Sex and Reproductive Status
a) Women who are pregnant or breastfeeding;
b) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period
and for up to 6 months after the study;
c) Women with a positive pregnancy test on enrollment or prior to investigational product administration;
d2) Target Disease Exceptions
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a) Any malignancy from which the patient has been disease-free for less than 2 years, with the exception of
adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ
of the cervix
b) Primary ocular melanoma.
3) Medical History and Concurrent Diseases
a) Symptomatic brain metastases requiring immediate local intervention (radiotherapy (RT) and/or surgery);
b) Leptominingeal involvement by disease;
c) Autoimmune disease: Patients with a documented history of Inflammatory Bowel Disease, including ulcerative
colitis and Crohn’s disease are excluded from this study as are patients with a documented history of
symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma],
Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener’s Granulomatosis] and autoimmune
hepatitis. Subjects with motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome) are
also excluded from this study;
d) Any underlying medical condition, which in the opinion of the investigator, will make the administration of
study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent
diarrhea.
4) Prohibited Treatments and/or Therapies
a) Concomitant therapy with any anti-cancer agent; immunosuppressive agents; any non-oncology vaccine therapy
used for prevention of infectious diseases (for up to 1 month prior to or after any dose of study drug); surgery or
radiotherapy (except palliative surgery and/or radiotherapy to treat a non-target symptomatic lesion or to the
brain after Sponsor approval); other investigational anti-cancer therapies; or chronic use of systemic
corticosteroids (used in the management of cancer or non-cancer-related illnesses);
b) Previous treatment with other investigational products, including cancer immunotherapy, within 30 days;
c) Prior treatment with anti-CTLA-4, except in adjuvant setting) Sexually active fertile men not using effective birth control if their partners are WOCBP

Study & Design

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