Sotatercept (ACE-011) With Lenalidomide or Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma

After the screening procedures confirm that you are eligible to participate in the research
study:

Assignment to dose level of study treatment Since we are looking for the highest dose of the
ACE 011 combined with lenalidomide that can be administered safely without severe or
unmanageable side effects in participants that have multiple myeloma, not everyone who
participates in this research study will receive the same dose of these drugs. The dose you
get will depend on the number of participants who have been enrolled in the study before you
and how well they have tolerated their doses.

Study treatment Study treatment will be given in 28 day cycles.

- ACE-011 will be given as an injection under the skin, Day 1 of each cycle (every 28
days). You will receive each injection at the clinic.

- Lenalidomide will be taken by mouth: once daily days 1 21, followed by a 7 day rest
period during which no lenalidomide will be taken.

- Dexamethasone will be taken by mouth once per week (days 1, 8, 15 and 22) of each cycle.

You will be given drug diaries to record the doses of lenalidomide and dexamethasone taken.
The study staff will tell you how to complete the diaries

Inclusion Criteria:

- Monoclonal plasma cells in the bone marrow > 10% and/or presence of a biopsy-proven
plasmacytoma

- Monoclonal protein present in the serum and/or urine

- Patient must have received at least 1 line of prior systemic therapy for the treatment
of multiple myeloma. A line of treatment is sequential treatment without interruption
for response and subsequent progression

- For participants treated with local radiotherapy with or without concomitant exposure
to steroids, for pain control or management of cord/nerve root compression, two weeks
must have lapsed since last date of radiotherapy, which is recommended to be a limited
field. Participants who require concurrent radiotherapy should have entry to the
protocol deferred until the radiotherapy is completed and two weeks have passed since
the last date of therapy.

- ECOG performance status of zero to two unless decline is due to bony disease

- Not pregnant or breastfeeding

Exclusion Criteria:

- Participants who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for
nitrosureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.

- Participants may not have received treatment with another investigational drug or
device within 28 days prior to Day 1, or if the half life of the previous product is
known, within 5 times the half life prior to dosing, whichever may be longer

- Participants 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.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ACE 011, Lenalidomide or Dexamethasone

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Individuals with a history of a different malignancy are ineligible except for the
following circumstances. Individuals with a history of other malignancies are eligible
if they have been disease-free for at least 5 years and are deemed by the investigator
to be at low risk for recurrence of that malignancy. Individuals with the following
cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer
in situ, and basal cell or squamous cell carcinoma of the skin.

- History of major surgery within 30 days prior to trial initiation