Medical Access Program for Ifinatamab Deruxtecan in 3L+ Pretreated Extensive-stage Small Cell Lung Cancer

Medical Access Program for Ifinatamab Deruxtecan (I-DXd, DS-7300a)

The purpose of this Medical Access Program (also referred to as an Expanded Access Program in the USA) is to provide access to I-DXd for eligible patients with extensive-stage small cell lung cancer (ES-SCLC) after two or more prior lines of treatment (including at least one platinum-based regimen), and for eligible patients who have no suitable treatment options and are not able to enter a clinical study.

A patient enrolled in this MAP can continue treatment until any of the following occurs (whichever comes first):

• Disease progression.
• Unacceptable toxicity.
• The benefit-risk no longer favors the individual.
• I-DXd becomes commercially available in the US, and reimbursement is approved for the treatment of ES-SCLC.
• The patient chooses to discontinue treatment.
• Withdrawal of consent.
• Pregnancy.
• Physician discretion.
• Death.

Patients are only eligible after signing the informed consent form and must meet all of the following criteria to be eligible for the Medical Access Program.

Inclusion Criteria:

• The patient has at least one SCLC lesion that has not been previously irradiated.
• The patient is aged ≥18 years or older.
• The patient has histologically or cytologically documented ES-SCLC.
• The patient had prior therapy with platinum-based chemotherapy and one additional treatment as systemic therapy for extensive-stage disease.
• The patient has received prior treatment with a minimum of two previous lines of systemic therapy.
• The patient has a documented radiological disease progression on or after the most recent systemic therapy.
• The patient has an ECOG PS of 0-1.
• The patient has a life expectancy of ≥3 months
• The patient has adequate organ and bone marrow function as defined in the protocol within 7 days prior to Cycle 1 Day 1 of I-DXd treatment. Transfusion (red blood cell or platelet) or granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 2 weeks prior to screening laboratory tests.
• Male and female patients of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the program and for at least 8 months for females and 5 months for males after the last dose of I-DXd.
• Female patients of childbearing potential must have a negative serum pregnancy test within 3 days prior to enrolment.
• Female patients agree to not donate, or retrieve for their own use, ova throughout the participation in the MAP and for 8 months following the last dose of I-DXd. Preservation of ova may be considered prior to enrolment in this program.
• Male patients are surgically sterile or willing to use highly effective birth control throughout the participation in the MAP and for 5 months following the last dose of I DXd.
• Male patients agree not to freeze or donate sperm throughout participation in the MAP and for 5 months following the last dose of I-DXd. Preservation of sperm may be considered prior to enrolment in this program.

Patients who meet any of the following criteria will not be eligible for the Medical Access Program.

Exclusion Criteria:

• The Patient is eligible for other treatment options or can enroll in an open clinical trial with patients with pre-treated ES-SCLC.

• The patient has received prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents, including I-DXd.

• The patient has been discontinued from an ADC that consists of an exatecan derivative (e.g., trastuzumab deruxtecan) due to treatment-related toxicities.

• The patient has had an inadequate washout period before randomization as defined in the protocol.

• The patient has clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.

• The patient has experienced any of the following events within the past 6 months:

  1. cerebrovascular accident, or
  2. transient ischemic attack, or
  3. another arterial thromboembolic event.

• The patient has a clinically significant corneal disease.

• The patient has uncontrolled or significant cardiovascular disease as defined in the protocol.

• The patient has any history of ILD/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at screening.

• The patient has a clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses as defined in the protocol.

• The patient is on chronic steroid treatment (dose of 10 mg daily or more prednisone equivalent), except for low-dose inhaled steroids (for asthma/COPD), topical steroids (for mild skin conditions), or intra-articular steroid injections.

• The patient has a history of allogeneic bone marrow, stem cell, or solid organ transplant.

• The patient has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE V5.0, Grade ≤1 or baseline.

• The patient has a history of hypersensitivity to the drug substances, inactive ingredients in the drug product, or severe hypersensitivity reactions to other monoclonal antibodies.

• The patient has a documented ongoing uncontrolled systemic bacterial, fungal, or viral infection.

• The patient has active or uncontrolled hepatitis B or C infection.

• The patient has an active, known, or suspected autoimmune disease. The following patients may be enrolled as an exception:

  1. Type I diabetes mellitus, hypothyroidism only requiring hormone replacement
  2. Skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or
  3. Conditions not expected to recur in the absence of an external trigger.

• The patient has any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses, psychiatric illness/social situations, substance abuse) or other factors that, in the physician's opinion, make it undesirable for the patient to participate in the MAP or would jeopardize compliance with the protocol. Screening for chronic conditions is not required.

• The patient has received a live vaccine within 30 days prior to the first dose of I-DXd.

• Female patients who are pregnant, breastfeeding, or intend to become pregnant during the MAP.

• The patient has active or uncontrolled human immunodeficiency virus (HIV) infection. Participants must be tested for HIV viral load before enrollment if acceptable by local regulations or independent review boards/Independent ethics committee.

• The patient has active or uncontrolled hepatitis B virus (HBV) infection. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have an undetectable HBV viral load prior to enrolment.

• The patient has active or uncontrolled hepatitis C virus (HCV) infection. Participants with a history of hepatitis C infection are eligible if the HCV viral load is undetectable in the absence of antiviral therapy during the previous 4 weeks.