Inclusion Criteria:

- Patients must have histologically or cytologically confirmed diagnosis of NSCLC.

- Patients must have non-squamous histology.

- Patients must have measurable disease (by RECIST criteria), defined as at least one
lesion that can be accurately measured in at least one dimension (longest diameter to
be recorded) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan.

- Patients may have failed at least one prior platinum-based therapy for NSCLC or be
candidates for first-line therapy for advanced disease deemed ineligible to receive
platinum-based chemotherapy in the opinion of the treating physician (e.g., ECOG
performance status of 2, age ≥ 70, chronic medical condition).

- 3.1.5 Patients must be at least 4 weeks out from chemotherapy, biological therapy,
major surgery, or any investigative therapy and must have recovered from any
toxicities. Patients must be at least 2 weeks out from prior radiation therapy and
must have recovered from any associated toxicities (with the exception of alopecia).

- Patients must be at least 3 weeks out from immunosuppressive therapy (except
corticosteroids used as antiemetics).

- Age ≥18 years. Because no dosing or adverse event data are currently available on
the use of pemetrexed in combination with temsirolimus in patients <18 years of age,
children are excluded from this study.

- Life expectancy of greater than 12 weeks.

- ECOG performance status 0-1.

- Patients must have normal organ and marrow function as defined below:

- hemoglobin ≥9.0 g/dL

- absolute neutrophil count ≥1,500/mcL

- platelets ≥100,000/mcL

- total bilirubin ≤1.5 mg/dL

- AST(SGOT)/ALT(SGPT) ≤2.5 X institutional upper limit of normal OR ≤5 X
institutional upper limit of normal if enzyme abnormalities are due to liver
metastases

- creatinine < 2.0 mg/dL AND/OR

- creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above
institutional normal

- serum cholesterol < 350 mg/dL

- triglycerides < 300 mg/dL

- The effects of pemetrexed and temsirolimus on the developing human fetus at the
recommended therapeutic dose are unknown. For this reason and because antifolate
antineoplastic agents as well as other therapeutic agents used in this trial are
known to be teratogenic, women of child-bearing potential and men must agree to use
adequate contraception (hormonal or barrier method of birth control; abstinence)
prior to study entry and for the duration of study participation. Should a woman
become pregnant or suspect she is pregnant while participating in this study, she
should inform her treating physician immediately.

- Ability of the patient (or legally authorized representative if applicable) to
understand and the willingness to sign a written informed consent document.

- Both men and women and members of all races and ethnic groups are eligible for this
trial.

Exclusion Criteria:

- Patients who have had previous treatment with pemetrexed.

- Patients may not be receiving any other investigational agents.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, clinically significant hepatic or renal disease or neuropathy greater
than grade 2.

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
events.

- Presence of a third-space fluid (pleural effusion, ascites etc.) that is uncontrolled
by drainage.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to temsirolimus, its metabolites (including sirolimus), its components,
and/or polysorbate 80, or to other agents used in the study.

- Known hypersensitivity to macrolide antibiotics.

- Patients with psychiatric illness/social situations that would limit compliance with
study requirements and with premedications of dexamethasone, folic acid and vitamin
B12.

- Patients with inability to discontinue all non-steroidal anti-inflammatory drugs
(NSAIDS).

- Patients taking anticonvulsant medications (Carbamezapine, phenytoin, fosphenytoin,
phenobarbital).

- Patients taking anti-arrhythmic medications (amiodarone, diltiazem and quinidine).

- 3.2.12 Patients may not be taking medications known as inhibitors of CYP3A4
(carbamezapine, phenytoin, phenobarbital, rifampin, St. John's wort). Please see
Appendix B for complete list. Use of inducers of CYP3A4 is discouraged but not
specifically prohibited. Dexamethasone as a chronic medication is discouraged.

- Pregnant women are excluded from this study because pemetrexed is an antifolate
antineoplastic drug with the potential for teratogenic or abortifacient effects.
Because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with pemetrexed, breastfeeding should be
discontinued if the mother is treated with pemetrexed. These potential risks may
also apply to other agents used in this study.

- Patients with known concomitant genetic or acquired immunosuppressive diseases are
excluded. HIV-positive patients on combination antiretroviral therapy are ineligible
because of the potential for pharmacokinetic interactions with pemetrexed and
temsirolimus. In addition, these patients are at increased risk of lethal infections
when treated with marrow-suppressive therapy. Appropriate studies will be undertaken
in patients receiving combination antiretroviral therapy when indicated.