A Phase 1, Open-label, Dose Finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CC-90011 in Subjects with Relapsed and/or Refractory Solid Tumors and Non-Hodgkin's Lymphomas

Phase 1

• Conditions: Relapsed/refractory advanced unresectable solid tumors and relapsed/refractory advanced NH

• Registration Number: JPRN-jRCT2031210081
• Lead Sponsor: Hatano Ben

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-05-11
• Last Update Posted: 17 October 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Subject is a man or woman >= 18 years of age, at the time of signing the informed consent form (ICF).
Entry Criteria Specific for Japanese cohort in Part B;
2. Subjects with histological or cytological confirmation of advanced unresectable solid tumors (including G2 NENs/NETs) and R/R NHLs (including DLBCL and FL or MZL)
Solid tumors;
- Participants must have received and either progressed or been intolerant to the standard treatment regimen in the advanced or metastatic setting, if such a therapy exists. Participants who refuse or are ineligible for standard therapy will be allowed to enroll provided their refusal/ineligibility is documented in medical records.
- Eligibility Criteria defined as following must be met for G2 NENs/NETs.
i. Appropriate pathological features according to WHO classification
ii. Expression of neuroendocrine markers (eg, synaptophysin or chromogranin-A) by immunohistochemistry
iii. Mitotic count >= 2 per 10 HPF or >= 2 per 2 mm^2 and/or >= 3% Ki67 index (if reliably available)
Specific additional criteria for certain NEC tumor types are as follows:
Small Cell Lung Cancer (SCLC);
- Histologic or cytologic confirmation of SCLC according to 2015 WHO classification or
- Immunohistochemistry suggestive of SCLC such as AE1/AE3 positive cytoplasmic staining, NCAM (CD56) positivity, chromogranin positivity, synaptophysin positivity, TTF1 positivity and high proliferation activity as demonstrated by Ki-67 in uncertain cases. Combined SCLC is permitted.
Large Cell Neuroendocrine Carcinoma (LCNEC);
- Histologic confirmation of LCNEC according to 2015 WHO classification
- Immunohistochemistry > 10% of tumor cells positive for CD56, chromogranin or synaptophysin. Combined LCNEC is permitted.
Neuroendocrine variant of EGFR mutant Lung Cancer;
- Known EGFR mutation
- Progression on/following prior EGFR inhibitor
- Histologic or cytologic confirmation of SCLC according to 2015 WHO Classification
- Immunohistochemistry suggestive of SCLC such as AE1/AE3 positive cytoplasmic staining, NCAM (CD56) positivity, chromogranin positivity, synaptophysin positivity, TTF1 positivity and high proliferation activity as demonstrated by Ki-67 in uncertain cases.
- Subjects with mixed adenoneuroendocrine carcinoma (MANEC), which has at least 30% adenocarcinoma and 30% NEC, are eligible.
Neuroendocrine Prostate Cancer (NEPC);
- Metastatic prostate cancer and at least one of
i. Histologic diagnosis of small cell or neuroendocrine prostate cancer, supported by immunochemistry
ii. Histologic diagnosis of prostate adenocarcinoma plus > 50% IHC staining for neuroendocrine markers [chromogranin, synaptophysin, CD56, or neuron-specific enolase (NSE)]
iii. Development of liver metastases in the absence of PSA progression as defined by PCWG3
- Subjects with histologic evidence of pure neuroendocrine or small cell carcinoma do not need to have received prior androgen deprivation therapy or castrate levels of testosterone, but their testosterone state should be maintained for the duration of the study. Other subjects must have undergone surgical or ongoing medical castration and have baseline serum testosterone levels < 50 ng/dL or < 1.73 nmol/L.
R/R NHLs;
- Subjects with relapsed/refractory NHLs after >= 2 prior therapies and ineligible for potentially curative therapy.
- Subjects must have progressed on (or not been able to tolerate due to medical comorbidities or unacceptable toxicity) standard anticancer therapy or for whom no other approved conv

Exclusion Criteria

1. G1 neuroendocrine tumors (< 2 per HPF or < 2 per mm^2 and/or <= 2% Ki67 index) such as carcinoid are excluded.
2. Subject has received anti-cancer therapy (either approved or investigational) <= 4 weeks or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1.
- < 42 days for prior nitrosoureas or mitomycin C
3. Toxicities resulting from prior systemic cancer therapies must have resolved to <= NCI CTCAE Grade 1 prior to starting CC-90011 treatment (with exception of grade 2 peripheral neuropathy and alopecia).
4. Prior autologous stem cell transplant <= 3 months before first dose or those who have not recovered.
5. Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning.
6. Subject has undergone major surgery <= 4 weeks or minor surgery <= 2 weeks prior to Cycle 1 Day 1 or who have not recovered from surgery.
7. Subject has completed any radiation treatment < 4 weeks prior to Cycle 1 Day 1 or < 2 weeks for palliative bone radiotherapy (single fraction). Subjects with > 25% of myelopoietic BM radiation are not allowed to be enrolled on this study.
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 GI disorder that could affect the absorption of CC-90011.
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 > CTCAE Grade 2 or haemoptysis > 1 teaspoon within 4 weeks prior to the first dose
11. Symptomatic and untreated or unstable central nervous system (CNS) metastases.
- Subject recently treated with whole brain radiation or stereotactic radiosurgery for CNS metastases must have completed therapy at least 4 weeks prior to Cycle 1, Day 1 and have a follow-up brain CT or MRI demonstrating either stable or improving metastases 4 or more weeks after completion of radiotherapy (the latter to be obtained as part of the Screening Assessments.)
- Subject must be asymptomatic and off steroids or on stable dose of steroids for at least 4 weeks (<=10 mg/day prednisone equivalent)
12. Subject with SCLC that has history of interstitial lung disease (ILD) OR a history of pneumonitis that has required oral or IV steroids
13. Subject has known symptomatic acute or chronic pancreatitis.
14. Subject has impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- LVEF < 45% as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO)
- Complete left bundle branch or bifascicular block
- Congenital long QT syndrome
- Persistent or clinically meaningful ventricular arrhythmias or atrial fibrillation.
- QTcF >= 480 msec on Screening ECG (mean of triplicate recordings)
- Unstable angina pectoris or myocardial infarction <= 6 months prior to starting CC-90011
15. Subject has other clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertension (blood pressure >= 160/95 mm Hg).
16. Subject is a pregnant or nursing female. Subject who is breastfeeding but agrees to stop breastfeeding during the study treatment and for at least 15 days after the last dose of CC- 90011, is considered eligible.
17. Subject has known HIV infection.
18. Subject has known chronic active hepatitis B or C virus (HBV, HCV) infect

Study & Design

• Study Type: Interventional
• Study Design: Not specified