| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Small cell lung cancer (SCLC) and squamous non-small cell lung cancer (sqNSCLC) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Different disease subtypes of lung cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10041071 |
| E.1.2 | Term | Small cell lung cancer stage unspecified |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10029514 |
| E.1.2 | Term | Non-small cell lung cancer NOS |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025126 |
| E.1.2 | Term | Lung squamous cell carcinoma stage unspecified |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective is to evaluate in each individual cohort the:
-Overall response rate (ORR) in subjects with SCLC or sqNSCLC treated with CC-90011 in combination with nivolumab |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate in each individual cohort the following endpoints/outcomes in subjects with SCLC or sqNSCLC receiving CC-90011 in combination with nivolumab:
-Safety and tolerability
-Duration of response (DoR)
-Time to response (TTR)
-Progression-free survival (PFS) assessed by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
-Overall survival (OS)
-Time to first subsequent therapy (TFST) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
2. Subject with histological or cytological confirmation of extensive stage SCLC (ES SCLC) or Stage IIIb or IV sqNSCLC.
3. Subject has received 1 or 2 prior lines of therapie (further defined in the protocol).
4. Subject has progressed at the last line of therapy.
5. Subject has a measurable disease defined by RECISTv1.1.
6. Subject agrees to provide a tumor biopsy from primary or metastatic site prior to first dose and at a pre-specified timepoint during treatment. Core biopsy is required however, in the event a core biopsy may not otherwise be feasible in the opinion of the treating physician, an endobronchial ultrasound-guided fine needle aspirate [EBUS-FNA]) biopsy, using the largest gauge needle, may be performed instead.
7. Subject has ECOG Performance Status of 0 to 1.
8. Subject is able to swallow medication.
9. Subject must have the lab values as specified in the protocol.
10.A female of childbearing potential (FCBP) is a female who:
1) has achieved menarche at some point,
2) has not undergone a hysterectomy or bilateral oophorectomy, or
3) has not been naturally postmenopausal (amenorrhea following cancer therapy or other medical condition does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) and must:
a. Have 2 negative pregnancy tests as verified by the Investigator prior to starting study treatments as specified in the protocol.
b. Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with 1 highly effective contraceptive method plus 1 barrier method during the following time periods related to this study: 1) from signing of ICF; 2) while taking study treatment; 3) during dose interruptions; and 4) for at least 45 days after the subject’s last dose of CC-90011 or 5 months after the last dose of nivolumab, whichever is later.
-Refer to the protocol for highly effective contraceptive methods.
c. Avoid conceiving or donating ova while on treatment and for 45 days after the last dose of CC-90011 or 5 months after the last dose of nivolumab, whichever is later.
d. Agree to ongoing pregnancy testing during the course of the study. This applies even if the subject practices true abstinence* from heterosexual contact.
11.Males must practice true abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use a condom (a latex or non-latex synthetic condom is recommended)during sexual contact with a pregnant female or a FCBP while participating in the study, during dose interruptions, and for at least 105 days after the subject’s last dose of CC-90011 or 7 months after the last dose of nivolumab, whichever is later, even if he has undergone a successful vasectomy. Males must agree not to donate semen or sperm while on treatment and for at least 105 days following the last dose of CC-90011 or 7 months after the last dose of nivolumab, whichever is later.
12.Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
13.Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
|
|
| E.4 | Principal exclusion criteria |
1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
3. Subject has any condition that confounds the ability to interpret data from the study.
4. Subject has not recovered to Grade 2 or lower clinically significant toxicities related to the prior therapy (alopecia excluded).
5. Subject has received prior LSD1 therapies.
6. Subject has a history of severe hypersensitivity reactions to other monoclonal antibodies.
7. Subject with symptomatic and untreated or unstable central nervous system (CNS) metastases.
8. Subject has persistent diarrhea due to a malabsorptive syndrome (such as celiac sprue or inflammatory bowel disease) ≥ NCI CTCAE Grade 2, despite medical management), or any other significant gastrointestinal (GI) disorder that could affect the absorption of the study treatments.
9. Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages.
10.Subject with any hemorrhage/bleeding event > NCI CTCAE Grade 2 or haemoptysis > 1 teaspoon within 4 weeks prior to the first dose.
11.Subject has any of the following cardiovascular criteria further specified in the protocol.
12.Subject has known human immunodeficiency virus (HIV) infection.
13.Subject has known chronic active hepatitis B or C virus (HBV, HCV) infection.
a. Subject who is seropositive due to HBV vaccination is eligible.
b. Subject who has no active viral infection and is under adequate prophylaxis against HBV reactivation is eligible.
14.Subject has any other malignancy within 2 years prior to enrollment, with the exception of adequately treated in-situ bladder cancer, in-situ carcinoma of the cervix, uteri, nonmelanomatous skin cancer, ductal in situ breast carcinoma, thyroid cancer, or early stage prostate cancer (all treatment of which should have been completed 6 months prior to enrollment).
15.Enrollment in any other clinical protocol or investigational study with an interventional agent or assessments that may interfere with study procedures.
16.Subject has medical conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of enrollment.
a. A brief (≤ 7 days) course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of nonautoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
b. Adrenal replacement steroid doses > 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease.
c. Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption) are permitted.
17.Subject has active autoimmune diseases or history of autoimmune diseases that may relapse. Subjects with the following diseases are allowed to be enrolled after further screening: type I diabetes, hypothyroidism managed with hormone replacement therapy only, skin diseases not requiring systemic treatment (such as vitiligo, psoriasis, or alopecia), or diseases not expected to recur in the absence of external triggering factors.
18.Subject is pregnant or nursing.
19.Subject has a history of persistent skin rash ≥ NCI CTCAE Grade 2 related to prior ICI therapy.
20.Subject has organ transplant history, including allogeneic stem cell transplant.
21.Subject has severe infection requiring a parenteral antibiotic treatment.
22.Subject has interstitial lung disease history.
23.Subject has received a live/attenuated vaccine within 30 days of first dose.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall Response Rate as defined as the proportion of subjects in the treated population who had confirmed complete response or confirmed partial response as assessed by Investigator review per RECIST v1.1. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Every 6 weeks post Cycle 1 Day 1 (C1D1) for the first 24 weeks and then every 8 weeks until disease progression, new anticancer therapy, death or withdrawal by subject. |
|
| E.5.2 | Secondary end point(s) |
-Safety and tolerability
-Duration of response
-Time to response
-Progression-free survival
-Overall survival
- Time to first subsequent therapy |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Safety and tolerability: From the time of signature of informed consent through 28 days after the last dose of CC-90011 and 100 days after the last dose of nivolumab.
-Duration of response: Every 6 weeks post C1D1 for the first 24 weeks and then every 8 weeks until disease progression, new anticancer therapy, death or withdrawal by subject.
- Time to response: Every 6 weeks post C1D1 for the first 24 weeks and then every 8 weeks until disease progression, new anticancer therapy, death or withdrawal by subject
-Progression-free survival: Every 6 weeks post C1D1 for the first 24 weeks and then every 8 weeks until disease progression, new anticancer therapy, death or withdrawal by subject
See protocol for further info about Overall survival and time to first subsequent therapy
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 29 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| France |
| Italy |
| Poland |
| Spain |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The End of Trial is defined as either the date of the last visit of the last subject to complete the post-treatment survival follow-up, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, whichever is the later date. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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