Prohibited Medications. Subjects who require treatment during the course of the study with either an anticonvulsant (phenobarbital, phenytoin, carbamazepin or primidone) or chronic treatment with any form of heparin will be discontinued. Estrogens given as HRT are allowed at entry into the study but cannot be initiated during the study except for local low dose vaginal estrogen. Drugs that may compromise renal function such as non-steroidal anti-inflammatory drugs should be used with caution.
Prohibited Medications. The use of the following medications is prohibited during the study: • Known CYP3A sensitive substrates, moderate or strong CYP3A inducers, and/or moderate or strong CYP3A inhibitors are prohibited throughout the study, until 1 week after the final administration of study intervention (See Section 10.9 for a full list of these medications). • Selected medications known to lower the seizure threshold and/or cause seizure (see Section 10.10 for a full list of these medications). • Medications known to significantly prolong the corrected QT interval (QTc)
Prohibited Medications. Known prior medications that exclude a patient from participating in this cohort are described in the exclusion criteria (see Section 8.2). Medications prohibited in the overall study are provided in the master protocol. The following additional therapies are prohibited during the screening and treatment phase for this cohort. • Investigational agents other than TSR-042, bevacizumab, and niraparib • Systemic glucocorticoids for any purpose other than to manage symptoms of suspected irAEIs. (Note: Use of inhaled steroids, local injection of steroids, topical steroids, and steroid eye drops are allowed.) If medically deemed necessary (eg, acute asthma or chronic obstructive pulmonary disease exacerbation, prophylaxis for IV contrast if indicated), Investigators are allowed to use their judgment to treat patients with systemic steroids. In such cases, systemic steroids should be stopped at least 24 hours prior to the next dose of TSR-042. • Prophylactic cytokines (ie, granulocyte colony-stimulating factor [GCSF]) should not be administered in the first cycle of the study but may be administered in subsequent cycles according to current American Society of Clinical Oncology (ASCO) guidelines.39 In addition, niraparib has been shown to weakly induce cytochrome P450 (CYP) 1A2 in vitro and is an insensitive substrate for P-glycoprotein. Therefore, Investigators and patients should be advised to use caution with drugs that are sensitive substrates of CYP1A2 with narrow therapeutic range, such as theophylline and tizanidine. The niraparib safety profile includes risk for thrombocytopenia, and bevacizumab may increase the potential for bleeding (hemorrhage); therefore, patients should be advised to use caution with anticoagulants (eg, warfarin) and antiplatelet drugs (eg, aspirin). Physicians should follow the current versions of the TSR-042 Investigator’s Brochure, the Zejula® package insert39, the Avastin® [Genentech/Roche US] package insert40, and the niraparib Investigator’s Brochure for information on the general management of the patients receiving these therapies.
Prohibited Medications. Medications specifically prohibited in the exclusion criteria are not allowed during the ongoing study (Section 5.2). The list of medications below is not exhaustive. If there are any questions regarding a medication, the investigator can consult with the Sponsor’s Medical Monitor (or designee). The following treatments are prohibited for all subjects during the study: • Phototherapy (PUVA and/or UVB) • All biologic therapy with a potential therapeutic impact on the disease being studied, including but not limited to the following: anakinra (Kineret®), abatacept (Orencia®), adalimumab (Humira®), natalizumab (Tysabri®), ustekinumab (Stelara®), etanercept (Enbrel®), infliximab (Remicade®), rituximab (Rituxan®), tocilizumab (Actemra®), efalizumab (Raptiva®), golimumab (Simponi®), certolizumab (Cimzia®), belimumab (Benlysta®), secukinumab (Cosentyx®) • Any investigational agents • Any oral antibiotic treatment for HS or other systemic non-biologic therapies with potential therapeutic impact on HS, including but not limited to antibiotics, methotrexate, cyclosporine, retinoids, corticosteroids, and fumaric acid esters • Live or live-attenuated vaccines (during the study and for 28 days after the last dose of study treatment) • New use of oral, topical, and opioid analgesics for HS • Prescription topical therapies for the treatment of HS, including topical steroids, calcineurin inhibitors, and phosphodiesterase inhibitors • New use of over-the-counter topical antiseptic washes, creams, soaps, ointments, gels, and liquids containing antibacterial agents to treat HS not listed in
Section 6.7.1 Surgical, intense pulsed light and laser intervention for an HS lesion except as outlined in Section 6.7.4 • Strong CYP3A inhibitors including but not limited to: cobicistat, boceprevir, ritonavir, indinavir, telaprevir, nelfinavir, danoprevir, dasabuvir, elvitegravir, lopinavir, ombitasvir, paritaprevir, saquinavir, tipranavir, itraconazole, ketoconazole, posaconazole, voriconazole, troleandomycin, clarithromycin, idelalisib, conivaptan, nefazodone • Strong CYP3A inducers including by not limited to: apalutamide carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. Xxxx’s wort
Prohibited Medications. Restrictions on specific classes of medications include the following and any use of these medications during the specified time periods must be documented as protocol deviations: • Initiation of new psychotropic medications, including antidepressant or antianxiety medications, and any new pharmacotherapy regimens that may potentially have an impact on efficacy and/or safety endpoints within 30 days prior to Day 1 through completion of the Day 45 visit • Use of any benzodiazepines, barbiturates, GABAA modulators (eg, eszopiclone, zopiclone, zaleplon, and zolpidem) within 28 days prior to Day 1 through completion of the Day 45 visit (within 30 days prior to Day 1 through completion of the Day 45 visit for benzodiazepine or GABA modulators with a half-life of ≥48 hours [eg, diazepam) • First generation (typical) antipsychotics (eg, haloperidol, perphenazine) and second generation (atypical) antipsychotics (eg, aripiprazole, quetiapine) within 14 days prior to Day 1 through completion of the Day 45 visit • Use of any non-GABA anti-insomnia medications (eg, melatonin, Benadryl [antihistamines], trazodone) within 14 days prior to Day 1 through completion of the Day 45 visit • Exposure to another investigational medication or device from 30 days prior to screening through completion of the Day 45 visit • Any known strong inhibitors of cytochrome P450 (CYP)3A4 within 14 days or 5 half-lives (whichever is longer) within 14 days prior to receiving the first dose of IP through the 14-day treatment period • Use of any strong CYP3A inducer, such as rifampin, carbamazepine, enzalutamide, mitotane, phenytoin, or St John’s Wort within 14 days or 5 half-lives (whichever is longer) prior to receiving the first dose of IP through the 14-day treatment period • Use of any chronic or as-needed psychostimulants (eg, methylphenidate, amphetamine) or opioids from within 28 days prior to Day 1 through completion of the Day 45 visit
