General Inclusion Criteria (for Dose Escalation, Expansion, and UPLIFT):
- ECOG performance status 0 or 1
- Measurable disease as per RECIST, version 1.1
- Resolution of all acute toxic effects of prior therapy or surgical procedures to
≤Grade 1 (except alopecia, stable immune-related toxicity such as hypothyroidism on
hormone replacement, adrenal insufficiency on ≤10 mg daily prednisone [or equivalent],
chronic Grade 2 peripheral sensory neuropathy after prior taxane therapy).
- Cardiac left ventricular ejection fraction (LVEF) ≥50% or ≥ the institution's lower
limit of normal by either Echo or MUGA scan
- Adequate organ function as defined by the following criteria:
1. Absolute neutrophil count (ANC) ≥1500 cells/mm3
2. Platelet count ≥100,000/mm3
3. Hemoglobin ≥9 g/dL
4. INR, activated partial thromboplastin time (aPTT), and prothrombin time (PT) all
within 1.2 times the institutional upper limit of normal (ULN) in the absence of
any other indicator of liver dysfunction. Patients on anticoagulants are allowed.
5. Estimated glomerular filtration rate (GFR) ≥45 mL/min
6. Total bilirubin ≤ULN
- Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT)
≤1.5 times the institutional ULN. Alkaline phosphatase (ALP) ≤1.5 times ULN unless
clearly attributable to a non-hepatic source, e.g., bone metastasis.
- Albumin ≥3.0 g/dL
- Able to provide informed consent.
General Exclusion Criteria (for Dose Escalation, Expansion, and UPLIFT) :
- Major surgery within 28 days of starting study treatment, systemic anti-cancer therapy
within the lesser of 28 days or 5 half-lives of the prior therapy before starting
study treatment, or recent radiation therapy with unresolved toxicity or within a time
window of potential toxicity.
- Patients with untreated CNS metastases (including new and progressive brain
metastases), history of leptomeningeal metastasis or carcinomatous meningitis.
- Current known active infection with HIV, hepatitis B virus, or hepatitis C virus.
- No prior history of liver disease such as liver cirrhosis, hepatic fibrosis
- Current severe, uncontrolled systemic disease (e.g., clinically significant
cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could
interfere with per-protocol evaluations.
- Severe dyspnea at rest due to complications of advanced malignancy, or requiring
supplementary oxygen therapy.
- Currently active pneumonitis or interstitial lung disease.
- Pregnant or nursing women.
- History of other malignancy within the last 2 years, except for appropriately treated
carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with
a similar expected curative outcome.
- Active corneal disease, or history of corneal disease within 12 months prior to
enrollment
- Use of strong CYP450 inhibitors
Ovarian Cancer Inclusion Criteria for UPLIFT:
- Histological diagnosis of high grade serous ovarian cancer, which includes fallopian
tube, or primary peritoneal cancer, that is metastatic or recurrent.
- Platinum-resistant disease
1. Patients who have only had 1 line of platinum-based therapy must have received at
least 4 cycles of platinum, must have had a response [complete response/remission
(CR) or partial response/remission (PR)], and then progressed between 3 months
and ≤ 6 months after the date of the last dose of platinum
2. Patients who have received 2 to 4 lines of prior therapy must have received at
least 4 cycles of platinum and then progressed within 6 months after the date of
the last dose of platinum
- One to 4 prior lines of systemic therapy for ovarian cancer
a. Prior treatment with bevacizumab is required for patients with 1 to 2 prior lines
of therapy
- Patients must be willing to provide an archival tumor tissue block or slides or if not
available, undergo procedure to obtain a new tumor biopsy using a low-risk, medically
routine procedure
Ovarian Cancer Exclusion Criteria for UPLIFT:
- Low-grade, clear cell, endometrioid, mucinous, carcinosarcoma, germ-cell, mixed
histology, or stromal tumors
- Prior treatment with mirvetuximab soravtansine or another ADC containing an
antitubulin payload
- Primary platinum-resistant disease, defined by a lack of response or by progression
within 3 months after completing front-line, platinum-containing therapy.
- Participation in DES or EXP segments of this study
Ovarian Cancer Inclusion Criteria for Expansion:
- Histological diagnosis of high grade serous ovarian cancer, which includes fallopian
tube, or primary peritoneal cancer, that is metastatic or recurrent.
- One to 3 prior lines of systemic therapy for ovarian cancer including at least 1 prior
line of a platinum-containing regimen. These patients must have platinum-resistant
disease, defined as completing 4 or more cycles of platinum-based therapy and
progressing within 6 months of last platinum-based therapy.
1. Patients with 4 lines of prior systemic therapy regardless of platinum
sensitivity status may be enrolled at the Investigator's discretion and upon
written approval by the Sponsor Medical Monitor.
2. Maintenance therapy, e.g., a PARP-inhibitor or bevacizumab given after a
platinum-containing regimen, will not count as a separate line of therapy.
- Tumor sample must be provided from both timepoints.
1. An archived tumor sample
2. A recent tumor biopsy (if medically feasible). If a recent biopsy cannot be
obtained, enrollment requires written approval by the Sponsor Medical Monitor.
Ovarian Cancer Exclusion Criteria for Expansion:
- Low-grade, clear cell, endometrioid, mucinous, carcinosarcoma, germ-cell, or stromal
tumors
- Prior treatment with mirvetuximab soravtansine or another ADC containing an auristatin
or maytansinoid payload
- More than 2 prior lines of treatment with a taxane-containing regimen.
- Primary platinum resistant disease, defined by a lack of response or progression
within 3 months after completing front-line, platinum-containing therapy
- Participation in the dose escalation segment of this study
NSCLC Inclusion Criteria for Expansion:
- Histological diagnosis of adenocarcinoma NSCLC, that is metastatic or recurrent
- One prior treatment regimen with a platinum-based therapy and 1 prior treatment
regimen with a PD-1 or PD-L1 monoclonal antibody (either in combination or
sequentially).
a. Patients previously treated with immunotherapy will require a washout phase of 4
weeks
- Patients with known oncogenic mutations for which there are approved therapies e.g.,
ALK translocation, EGFR mutation, must have received appropriate targeted therapy in
addition to a platinum-based regimen. Prior treatment with a PD1/L1 is not required
for these patients.
- One or 2 prior lines of chemotherapy
- Head CT or MRI within 3 months prior to initiation of screening procedures or may be
done during screening
a. Patients with history of brain metastases must have brain imaging within 4 weeks
prior to or during screening
- Tumor sample must be provided from both timepoints.
1. An archived tumor sample
2. A recent tumor biopsy (if medically feasible)
NSCLC Exclusion Criteria for Expansion:
- Histologies other than adenocarcinoma, e.g., large cell, squamous cell, or
adenosquamous
- Prior treatment with an ADC containing auristatin or maytansinoid payload
- More than one prior line of immunotherapy
- Participation in the dose escalation segment of this study
